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<span>Structure</span> </div> </a> <button aria-controls="toc-Structure-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Structure subsection</span> </button> <ul id="toc-Structure-sublist" class="vector-toc-list"> <li id="toc-Gene" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Gene"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.1</span> <span>Gene</span> </div> </a> <ul id="toc-Gene-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Protein" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Protein"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2</span> <span>Protein</span> </div> </a> <ul id="toc-Protein-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Polymorphisms" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" 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Available in 19 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-19" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">19 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%B5%D9%85%D9%8A%D9%85_%D8%A7%D9%84%D8%A8%D8%B1%D9%88%D8%AA%D9%8A%D9%86_%D8%A7%D9%84%D8%B4%D8%AD%D9%85%D9%8A_E" title="صميم البروتين الشحمي E – Arabic" lang="ar" hreflang="ar" data-title="صميم البروتين الشحمي E" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/Apolipoprotein_E" title="Apolipoprotein E – Bosnian" lang="bs" hreflang="bs" data-title="Apolipoprotein E" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Apolipoprote%C3%AFna_E" title="Apolipoproteïna E – Catalan" lang="ca" hreflang="ca" data-title="Apolipoproteïna E" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-cy mw-list-item"><a href="https://cy.wikipedia.org/wiki/APOE" title="APOE – Welsh" lang="cy" hreflang="cy" data-title="APOE" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target"><span>Cymraeg</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Apolipoprotein_E" title="Apolipoprotein E – German" lang="de" hreflang="de" data-title="Apolipoprotein E" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Apolipoprote%C3%ADna_E" title="Apolipoproteína E – Spanish" lang="es" hreflang="es" data-title="Apolipoproteína E" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%A2%D9%BE%D9%88%D9%84%DB%8C%D9%BE%D9%88%D9%BE%D8%B1%D9%88%D8%AA%D8%A6%DB%8C%D9%86_%D8%A6%DB%8C" title="آپولیپوپروتئین ئی – Persian" lang="fa" hreflang="fa" data-title="آپولیپوپروتئین ئی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Apolipoprot%C3%A9ine_E" title="Apolipoprotéine E – French" lang="fr" hreflang="fr" data-title="Apolipoprotéine E" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Apolipoprote%C3%ADna_E" title="Apolipoproteína E – Galician" lang="gl" hreflang="gl" data-title="Apolipoproteína E" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-hr mw-list-item"><a href="https://hr.wikipedia.org/wiki/Apolipoprotein_E" title="Apolipoprotein E – Croatian" lang="hr" hreflang="hr" data-title="Apolipoprotein E" data-language-autonym="Hrvatski" data-language-local-name="Croatian" class="interlanguage-link-target"><span>Hrvatski</span></a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Apolipoproteinum_E" title="Apolipoproteinum E – Latin" lang="la" hreflang="la" data-title="Apolipoproteinum E" data-language-autonym="Latina" data-language-local-name="Latin" class="interlanguage-link-target"><span>Latina</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Apolipoprote%C3%AFne_E" title="Apolipoproteïne E – Dutch" lang="nl" hreflang="nl" data-title="Apolipoproteïne E" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E3%82%A2%E3%83%9D%E3%83%AA%E3%83%9D%E3%83%97%E3%83%AD%E3%83%86%E3%82%A4%E3%83%B3E" title="アポリポプロテインE – Japanese" lang="ja" hreflang="ja" data-title="アポリポプロテインE" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Apolipoproteina_E" title="Apolipoproteina E – Polish" lang="pl" hreflang="pl" data-title="Apolipoproteina E" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Apolipoprote%C3%ADna_E" title="Apolipoproteína E – Portuguese" lang="pt" hreflang="pt" data-title="Apolipoproteína E" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%90%D0%BF%D0%BE%D0%BB%D0%B8%D0%BF%D0%BE%D0%BF%D1%80%D0%BE%D1%82%D0%B5%D0%B8%D0%BD_E" title="Аполипопротеин E – Russian" lang="ru" hreflang="ru" data-title="Аполипопротеин E" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/Apolipoproteiini_E" title="Apolipoproteiini E – Finnish" lang="fi" hreflang="fi" data-title="Apolipoproteiini E" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target"><span>Suomi</span></a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/Apolipoprotein_E" title="Apolipoprotein E – Turkish" lang="tr" hreflang="tr" data-title="Apolipoprotein E" data-language-autonym="Türkçe" data-language-local-name="Turkish" class="interlanguage-link-target"><span>Türkçe</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%90%D0%BF%D0%BE%D0%BB%D1%96%D0%BF%D0%BE%D0%BF%D1%80%D0%BE%D1%82%D0%B5%D1%97%D0%BD_E" title="Аполіпопротеїн E – Ukrainian" lang="uk" hreflang="uk" data-title="Аполіпопротеїн E" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target"><span>Українська</span></a></li> </ul> <div class="after-portlet after-portlet-lang"><span class="wb-langlinks-edit wb-langlinks-link"><a href="https://www.wikidata.org/wiki/Special:EntityPage/Q424728#sitelinks-wikipedia" title="Edit interlanguage links" class="wbc-editpage">Edit links</a></span></div> </div> </div> </div> </header> <div class="vector-page-toolbar"> <div class="vector-page-toolbar-container"> <div id="left-navigation"> <nav 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typeof="mw:File"><a href="/wiki/File:ApoE_22k_fragment_2001.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/8/81/ApoE_22k_fragment_2001.png/250px-ApoE_22k_fragment_2001.png" decoding="async" width="250" height="133" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/81/ApoE_22k_fragment_2001.png/375px-ApoE_22k_fragment_2001.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/81/ApoE_22k_fragment_2001.png/500px-ApoE_22k_fragment_2001.png 2x" data-file-width="4495" data-file-height="2391" /></a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Available structures</th></tr><tr><th rowspan="2" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;width:43px"><a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a></th><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit">Ortholog search: <span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/searchResults.html?display=both&term=P08226%20or%20P02649">PDBe</a> <a rel="nofollow" class="external text" href="https://www.rcsb.org/search?q=rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_name:UniProt%20AND%20rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_accession:P08226,P02649">RCSB</a> </span></td></tr><tr><td><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr style="text-align:center"><th colspan="2" style="background-color:light-dark(#ddd, #404244) !important;color:inherit">List of PDB id codes</th></tr><tr><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1B68">1B68</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1BZ4">1BZ4</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1EA8">1EA8</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1GS9">1GS9</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1H7I">1H7I</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1LE2">1LE2</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1LE4">1LE4</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1LPE">1LPE</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1NFN">1NFN</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1NFO">1NFO</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1OEF">1OEF</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1OEG">1OEG</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1OR2">1OR2</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1OR3">1OR3</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/2KC3">2KC3</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/2KNY">2KNY</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/2L7B">2L7B</a></span></p></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Identifiers</th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Gene_nomenclature" title="Gene nomenclature">Aliases</a></span></th><td colspan="3" style="background:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/613">APOE</a></span>, AD2, APO-E, LDLCQ5, LPG, apolipoprotein E, ApoE4</td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">External IDs</th><td colspan="3" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Mendelian_Inheritance_in_Man" class="mw-redirect" title="Mendelian Inheritance in Man">OMIM</a>: <a rel="nofollow" class="external text" href="https://omim.org/entry/107741">107741</a>; <a href="/wiki/Mouse_Genome_Informatics" title="Mouse Genome Informatics">MGI</a>: <a rel="nofollow" class="external text" href="http://www.informatics.jax.org/marker/MGI:88057">88057</a>; <a href="/wiki/HomoloGene" title="HomoloGene">HomoloGene</a>: <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=HomoloGene&list_uids=30951">30951</a>; <a href="/wiki/GeneCards" title="GeneCards">GeneCards</a>: <a rel="nofollow" class="external text" href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=APOE">APOE</a>; <a href="/wiki/Orthologous_MAtrix" title="Orthologous MAtrix">OMA</a>:<a rel="nofollow" class="external text" href="https://omabrowser.org/oma/vps/ENSG00000130203">APOE - orthologs</a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Gene location (<a href="/wiki/Human_genome" title="Human genome">Human</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:Ideogram_human_chromosome_19.svg" class="mw-file-description" title="Chromosome 19 (human)"><img alt="Chromosome 19 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/5/54/Ideogram_human_chromosome_19.svg/300px-Ideogram_human_chromosome_19.svg.png" decoding="async" width="300" height="120" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/54/Ideogram_human_chromosome_19.svg/450px-Ideogram_human_chromosome_19.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/54/Ideogram_human_chromosome_19.svg/600px-Ideogram_human_chromosome_19.svg.png 2x" data-file-width="474" data-file-height="189" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Chromosome_19_(human)" class="mw-redirect" title="Chromosome 19 (human)">Chromosome 19 (human)</a><sup id="cite_ref-refGRCh38Ensembl_1-0" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Human_chromosome_19_ideogram.svg" class="mw-file-description" title="Chromosome 19 (human)"><img alt="Chromosome 19 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/b/b6/Human_chromosome_19_ideogram.svg/300px-Human_chromosome_19_ideogram.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/b6/Human_chromosome_19_ideogram.svg/450px-Human_chromosome_19_ideogram.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/b6/Human_chromosome_19_ideogram.svg/600px-Human_chromosome_19_ideogram.svg.png 2x" data-file-width="1125" data-file-height="216" /></a></span><div style="position: absolute; left: 219.93863777835px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for APOE"><img alt="Genomic location for APOE" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 225.9px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for APOE"><img alt="Genomic location for APOE" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">19q13.32</span></td><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Start</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">44,905,791 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-1" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">End</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">44,909,393 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-2" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Gene location (<a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:Ideogram_house_mouse_chromosome_7.svg" class="mw-file-description" title="Chromosome 7 (mouse)"><img alt="Chromosome 7 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/Ideogram_house_mouse_chromosome_7.svg/260px-Ideogram_house_mouse_chromosome_7.svg.png" decoding="async" width="260" height="111" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/Ideogram_house_mouse_chromosome_7.svg/390px-Ideogram_house_mouse_chromosome_7.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e4/Ideogram_house_mouse_chromosome_7.svg/520px-Ideogram_house_mouse_chromosome_7.svg.png 2x" data-file-width="470" data-file-height="200" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">Chromosome 7 (mouse)<sup id="cite_ref-refGRCm38Ensembl_2-0" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Ideogram_of_house_mouse_chromosome_7.svg" class="mw-file-description" title="Chromosome 7 (mouse)"><img alt="Chromosome 7 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/2/2c/Ideogram_of_house_mouse_chromosome_7.svg/300px-Ideogram_of_house_mouse_chromosome_7.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/2c/Ideogram_of_house_mouse_chromosome_7.svg/450px-Ideogram_of_house_mouse_chromosome_7.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/2c/Ideogram_of_house_mouse_chromosome_7.svg/600px-Ideogram_of_house_mouse_chromosome_7.svg.png 2x" data-file-width="1200" data-file-height="231" /></a></span><div style="position: absolute; left: 33.897397962641px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for APOE"><img alt="Genomic location for APOE" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 39.9px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for APOE"><img alt="Genomic location for APOE" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">7 A3|7 9.94 cM</span></td><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Start</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">19,430,034 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-1" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">End</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">19,433,113 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-2" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Gene_expression" title="Gene expression">RNA expression</a> pattern</th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a rel="nofollow" class="external text" href="https://www.bgee.org/">Bgee</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th><b><a href="/wiki/Human_genome" title="Human genome">Human</a></b></th><th><b><a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a> (ortholog)</b></th></tr><tr><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000130203">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">right adrenal cortex</li><br /><li style="line-height: 137%;">left adrenal gland</li><br /><li style="line-height: 137%;">left adrenal cortex</li><br /><li style="line-height: 137%;">right lobe of liver</li><br /><li style="line-height: 137%;">nucleus accumbens</li><br /><li style="line-height: 137%;">Amygdala</li><br /><li style="line-height: 137%;">Hypothalamus</li><br /><li style="line-height: 137%;">caudate nucleus</li><br /><li style="line-height: 137%;">C1 segment</li><br /><li style="line-height: 137%;">putamen</li></ul></div></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSMUSG00000002985">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">entorhinal cortex</li><br /><li style="line-height: 137%;">stroma of bone marrow</li><br /><li style="line-height: 137%;">choroid plexus of fourth ventricle</li><br /><li style="line-height: 137%;">perirhinal cortex</li><br /><li style="line-height: 137%;">CA3 field</li><br /><li style="line-height: 137%;">left lobe of liver</li><br /><li style="line-height: 137%;">dentate gyrus of hippocampal formation granule cell</li><br /><li style="line-height: 137%;">yolk sac</li><br /><li style="line-height: 137%;">gallbladder</li><br /><li style="line-height: 137%;">superior frontal gyrus</li></ul></div></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000130203">More reference expression data</a></span></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a rel="nofollow" class="external text" href="http://biogps.org/">BioGPS</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:PBB_GE_APOE_203382_s_at_fs.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/1c/PBB_GE_APOE_203382_s_at_fs.png/250px-PBB_GE_APOE_203382_s_at_fs.png" decoding="async" width="250" height="181" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/1c/PBB_GE_APOE_203382_s_at_fs.png/375px-PBB_GE_APOE_203382_s_at_fs.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/1c/PBB_GE_APOE_203382_s_at_fs.png/500px-PBB_GE_APOE_203382_s_at_fs.png 2x" data-file-width="732" data-file-height="530" /></a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="http://biogps.org/gene/348/">More reference expression data</a></span></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Gene_ontology" class="mw-redirect" title="Gene ontology">Gene ontology</a></th></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Molecular function</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008201">heparin binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070326">very-low-density lipoprotein particle receptor binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0050750">low-density lipoprotein particle receptor binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0071813">lipoprotein particle binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0060228">phosphatidylcholine-sterol O-acyltransferase activator activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005543">phospholipid binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0120020">cholesterol transfer activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042803">protein homodimerization activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0001540">amyloid-beta binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005515">protein binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0048156">tau protein binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0046911">metal chelating activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005319">lipid transporter activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0015485">cholesterol binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016209">antioxidant activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042802">identical protein binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008289">lipid binding</a></li></ul> </div></td></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Cellular component</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005737">cytoplasm</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016020">membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042627">chylomicron</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005576">extracellular region</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005634">nucleus</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1903561">extracellular vesicle</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0071682">endocytic vesicle lumen</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034361">very-low-density lipoprotein particle</a></li> <li><a href="https://www.wikidata.org/wiki/Q2914458" class="extiw" title="d:Q2914458">extracellular fluid</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005783">endoplasmic reticulum</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070062">extracellular exosome</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005794">Golgi apparatus</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0072562">blood microparticle</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0031012">extracellular matrix</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005886">plasma membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043025">soma</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005769">early endosome</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034362">low-density lipoprotein particle</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0030425">dendrite</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034364">high-density lipoprotein particle</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034363">intermediate-density lipoprotein particle</a></li></ul> </div></td></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Biological process</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043524">negative regulation of neuron apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002021">response to dietary excess</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1903001">negative regulation of lipid transport across blood-brain barrier</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006869">lipid transport</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0046889">positive regulation of lipid biosynthetic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0030516">regulation of axon extension</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901628">positive regulation of postsynaptic membrane organization</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0010873">positive regulation of cholesterol esterification</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0033700">phospholipid efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006707">cholesterol catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0060999">positive regulation of dendritic spine development</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006898">receptor-mediated endocytosis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0001523">retinoid metabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902004">positive regulation of amyloid-beta formation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0055088">lipid homeostasis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042158">lipoprotein biosynthetic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042632">cholesterol homeostasis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0050728">negative regulation of inflammatory response</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006641">triglyceride metabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0090090">negative regulation of canonical Wnt signaling pathway</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902951">negative regulation of dendritic spine maintenance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043537">negative regulation of blood vessel endothelial cell migration</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0097114">NMDA glutamate receptor clustering</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0000302">response to reactive oxygen species</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0030195">negative regulation of blood coagulation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006979">response to oxidative stress</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0051000">positive regulation of nitric-oxide synthase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902999">negative regulation of phospholipid efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0010875">positive regulation of cholesterol efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043407">negative regulation of MAP kinase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0048844">artery morphogenesis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034372">very-low-density lipoprotein particle remodeling</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0048168">regulation of neuronal synaptic plasticity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0061000">negative regulation of dendritic spine development</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0045541">negative regulation of cholesterol biosynthetic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902952">positive regulation of dendritic spine maintenance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902995">positive regulation of phospholipid efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901630">negative regulation of presynaptic membrane organization</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901215">negative regulation of neuron death</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034384">high-density lipoprotein particle clearance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0015909">long-chain fatty acid transport</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042157">lipoprotein metabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902947">regulation of tau-protein kinase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007186">G protein-coupled receptor signaling pathway</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034382">chylomicron remnant clearance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006874">cellular calcium ion homeostasis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008203">cholesterol metabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034447">very-low-density lipoprotein particle clearance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0019068">virion assembly</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0051055">negative regulation of lipid biosynthetic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0019934">cGMP-mediated signaling</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0019433">triglyceride catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901631">positive regulation of presynaptic membrane organization</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902998">positive regulation of neurofibrillary tangle assembly</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0097113">AMPA glutamate receptor clustering</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0032805">positive regulation of low-density lipoprotein particle receptor catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1903002">positive regulation of lipid transport across blood-brain barrier</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0055089">fatty acid homeostasis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007263">nitric oxide mediated signal transduction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006810">transport</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0033344">cholesterol efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0010468">regulation of gene expression</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0090370">negative regulation of cholesterol efflux</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1900221">regulation of amyloid-beta clearance</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0031102">neuron projection regeneration</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901627">negative regulation of postsynaptic membrane organization</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008202">steroid metabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0032489">regulation of Cdc42 protein signal transduction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006629">lipid metabolism</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1902430">negative regulation of amyloid-beta formation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0051044">positive regulation of membrane protein ectodomain proteolysis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042311">vasodilation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0046907">intracellular transport</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007271">synaptic transmission, cholinergic</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901216">positive regulation of neuron death</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034380">high-density lipoprotein particle assembly</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0017038">protein import</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034375">high-density lipoprotein particle remodeling</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0001937">negative regulation of endothelial cell proliferation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0051651">maintenance of location in cell</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0010544">negative regulation of platelet activation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0034374">low-density lipoprotein particle remodeling</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0044794">positive regulation by host of viral process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007010">cytoskeleton organization</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:1901214">regulation of neuron death</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043691">reverse cholesterol transport</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042159">lipoprotein catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070328">triglyceride homeostasis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0098869">cellular oxidant detoxification</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0010877">lipid transport involved in lipid storage</a></li></ul> </div></td></tr><tr><td colspan="4" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center">Sources:<a rel="nofollow" class="external text" href="http://amigo.geneontology.org/">Amigo</a> / <a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/QuickGO/">QuickGO</a></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Orthologs" class="mw-redirect" title="Orthologs">Orthologs</a></th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Species</th><td><b>Human</b></td><td><b>Mouse</b></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Entrez" title="Entrez">Entrez</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=348&rn=1">348</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=11816&rn=1">11816</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Ensembl" class="mw-redirect" title="Ensembl">Ensembl</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000130203;db=core">ENSG00000130203</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Mus_musculus/geneview?gene=ENSMUSG00000002985;db=core">ENSMUSG00000002985</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/UniProt" title="UniProt">UniProt</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/P02649">P02649</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/P08226">P08226</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">RefSeq (mRNA)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001302691">NM_001302691</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_000041">NM_000041</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001302688">NM_001302688</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001302689">NM_001302689</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001302690">NM_001302690</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_009696">NM_009696</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001305819">NM_001305819</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001305843">NM_001305843</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001305844">NM_001305844</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">RefSeq (protein)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_000032">NP_000032</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001289617">NP_001289617</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001289618">NP_001289618</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001289619">NP_001289619</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001289620">NP_001289620</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001292748">NP_001292748</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001292772">NP_001292772</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001292773">NP_001292773</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_033826">NP_033826</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Location (UCSC)</th><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&position=chr19:44905791-44909393">Chr 19: 44.91 – 44.91 Mb</a></span></td><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Mouse&db=mm0&position=chr7:19430034-19433113">Chr 7: 19.43 – 19.43 Mb</a></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/PubMed" title="PubMed">PubMed</a> search</th><td><span class="plainlinks"><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></span></td><td><span class="plainlinks"><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><a href="/wiki/Wikidata" title="Wikidata">Wikidata</a></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center"><a href="https://www.wikidata.org/wiki/Q14890468" class="extiw" title="d:Q14890468">View/Edit Human</a></td><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center"><a href="https://www.wikidata.org/wiki/Q14890475" class="extiw" title="d:Q14890475">View/Edit Mouse</a></td></tr></tbody></table></td></tr></tbody></table> <p><b>Apolipoprotein E</b> (<b>Apo-E</b>) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a> and <a href="/wiki/Cardiovascular_disease" title="Cardiovascular disease">cardiovascular diseases</a>.<sup id="cite_ref-encyclopedia_5-0" class="reference"><a href="#cite_note-encyclopedia-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> It is encoded in humans by the <a href="/wiki/Gene" title="Gene">gene</a> <i>APOE</i>. </p><p>Apo-E belongs to a family of fat-binding proteins called <a href="/wiki/Apolipoprotein" title="Apolipoprotein">apolipoproteins</a>. In the circulation, it is present as part of several classes of lipoprotein particles, including <a href="/wiki/Chylomicron_remnants" class="mw-redirect" title="Chylomicron remnants">chylomicron remnants</a>, <a href="/wiki/VLDL" class="mw-redirect" title="VLDL">VLDL</a>, <a href="/wiki/Intermediate-density_lipoprotein" title="Intermediate-density lipoprotein">IDL</a>, and some <a href="/wiki/High-density_lipoprotein" title="High-density lipoprotein">HDL</a>.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> Apo-E interacts significantly with the <a href="/wiki/LDL_receptor" title="LDL receptor">low-density lipoprotein receptor (LDLR)</a>, which is essential for the normal processing (<a href="/wiki/Catabolism" title="Catabolism">catabolism</a>) of <a href="/wiki/Triglyceride" title="Triglyceride">triglyceride</a>-rich lipoproteins.<sup id="cite_ref-entrez_7-0" class="reference"><a href="#cite_note-entrez-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> In peripheral tissues, Apo-E is primarily produced by the <a href="/wiki/Liver" title="Liver">liver</a> and <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>, and mediates <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> metabolism. In the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a>, Apo-E is mainly produced by <a href="/wiki/Astrocytes" class="mw-redirect" title="Astrocytes">astrocytes</a> and transports <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> to <a href="/wiki/Neurons" class="mw-redirect" title="Neurons">neurons</a><sup id="cite_ref-Wang_2020.06.18.159632_8-0" class="reference"><a href="#cite_note-Wang_2020.06.18.159632-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> via Apo-E receptors, which are members of the <a href="/wiki/Low_density_lipoprotein_receptor_gene_family" class="mw-redirect" title="Low density lipoprotein receptor gene family">low density lipoprotein receptor gene family</a>.<sup id="cite_ref-Liu2013_9-0" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Apo-E is the principal cholesterol carrier in the brain.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Apo-E qualifies as a <a href="/wiki/Checkpoint_inhibitor" title="Checkpoint inhibitor">checkpoint inhibitor</a> of the <a href="/wiki/Classical_complement_pathway" title="Classical complement pathway">classical complement pathway</a> by complex formation with activated <a href="/wiki/Complement_component_1q" title="Complement component 1q">C1q</a>.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Evolution">Evolution</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=1" title="Edit section: Evolution"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Apolipoproteins are not unique to mammals. Many terrestrial and marine <a href="/wiki/Vertebrate" title="Vertebrate">vertebrates</a> have versions of them.<sup id="cite_ref-Babin_1997_12-0" class="reference"><a href="#cite_note-Babin_1997-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> It is believed that <i>APOE</i> arose via gene duplications of <i><a href="/wiki/APOC1" class="mw-redirect" title="APOC1">APOC1</a></i> before the fish–<a href="/wiki/Tetrapoda" class="mw-redirect" title="Tetrapoda">tetrapod</a> split ca. 400 million years ago. Proteins similar in function have been found in <a href="/wiki/Choanoflagellate" title="Choanoflagellate">choanoflagellates</a>, suggesting that they are a very old class of proteins predating the dawn of all living animals.<sup id="cite_ref-Huebbe_2017_13-0" class="reference"><a href="#cite_note-Huebbe_2017-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p><p>The three major human <a href="/wiki/Allele" title="Allele">alleles</a> (<i>E4</i>, <i>E3</i>, <i>E2</i>) arose after the primate–human split around 7.5 million years ago. These alleles are the by-product of non-synonymous mutations which led to changes in functionality. The first allele to emerge was E4. After the primate–human split, there were four amino acid changes in the human lineage, three of which had no effect on protein function (V174L, A18T, A135V). The fourth substitution (T61R) traded a threonine for an arginine altering the protein's functionality. This substitution occurred somewhere in the 6 million year gap between the primate–human split and the <a href="/wiki/Denisovan" title="Denisovan">Denisovan</a>–human split, since exactly the same substitutions were found in Denisovan <i>APOE</i>.<sup id="cite_ref-McIntosh_2012_14-0" class="reference"><a href="#cite_note-McIntosh_2012-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>About 220,000 years ago, a cysteine to arginine substitution took place at amino acid 112 (Cys112Arg) of the <i>APOE4</i> gene, and this resulted in the <i>E3</i> allele. Finally, 80,000 years ago, another arginine to cysteine substitution at amino acid 158 (Arg158Cys) of the <i>APOE3</i> gene created the <i>E2</i> allele.<sup id="cite_ref-pmid15101252_15-0" class="reference"><a href="#cite_note-pmid15101252-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Huebbe_2017_13-1" class="reference"><a href="#cite_note-Huebbe_2017-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Structure">Structure</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=2" title="Edit section: Structure"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Gene">Gene</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=3" title="Edit section: Gene"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The gene, <i>APOE</i>, is mapped to <a href="/wiki/Chromosome_19_(human)" class="mw-redirect" title="Chromosome 19 (human)">chromosome 19</a> in a <a href="/wiki/Gene_cluster" title="Gene cluster">cluster</a> with the <a href="/wiki/Apolipoprotein_C1" class="mw-redirect" title="Apolipoprotein C1">apolipoprotein C1</a> (<i>APOC1</i>) gene and the <a href="/wiki/Apolipoprotein_C2" class="mw-redirect" title="Apolipoprotein C2">apolipoprotein C2</a> (<i>APOC2</i>) gene. The <i>APOE</i> gene consists of four <a href="/wiki/Exons" class="mw-redirect" title="Exons">exons</a> and three <a href="/wiki/Introns" class="mw-redirect" title="Introns">introns</a>, totaling 3597 <a href="/wiki/Base_pair" title="Base pair">base pairs</a>. <i>APOE</i> is transcriptionally activated by the <a href="/wiki/Liver_X_receptor" title="Liver X receptor">liver X receptor</a> (an important regulator of <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a>, <a href="/wiki/Fatty_acid" title="Fatty acid">fatty acid</a>, and <a href="/wiki/Glucose" title="Glucose">glucose</a> <a href="/wiki/Homeostasis" title="Homeostasis">homeostasis</a>) and <a href="/wiki/Peroxisome_proliferator-activated_receptor" title="Peroxisome proliferator-activated receptor">peroxisome proliferator-activated receptor</a> γ, <a href="/wiki/Nuclear_receptor" title="Nuclear receptor">nuclear receptors</a> that form <a href="/wiki/Heterodimer" class="mw-redirect" title="Heterodimer">heterodimers</a> with <a href="/wiki/Retinoid_X_receptor" title="Retinoid X receptor">retinoid X receptors</a>.<sup id="cite_ref-pmid11172721_16-0" class="reference"><a href="#cite_note-pmid11172721-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> In <a href="/wiki/Melanocyte" title="Melanocyte">melanocytic cells</a> <i>APOE</i> gene expression may be regulated by <a href="/wiki/Microphthalmia-associated_transcription_factor" title="Microphthalmia-associated transcription factor">MITF</a>.<sup id="cite_ref-pmid19067971_17-0" class="reference"><a href="#cite_note-pmid19067971-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Protein">Protein</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=4" title="Edit section: Protein"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Apoe-E is 299 <a href="/wiki/Amino_acid" title="Amino acid">amino acids</a> long and contains multiple <a href="/wiki/Amphipathic" class="mw-redirect" title="Amphipathic">amphipathic</a> <a href="/wiki/%CE%91-helices" class="mw-redirect" title="Α-helices">α-helices</a>. According to crystallography studies, a hinge region connects the N- and C-terminal regions of the protein. The N-terminal region (<a href="/wiki/Residue_(chemistry)#Biochemistry" title="Residue (chemistry)">residues</a> 1–167) forms an anti-parallel four-helix bundle such that the non-polar sides face inside the protein. Meanwhile, the C-terminal domain (residues 206–299) contains three α-helices which form a large exposed <a href="/wiki/Hydrophobic" class="mw-redirect" title="Hydrophobic">hydrophobic</a> surface and interact with those in the N-terminal helix bundle domain through <a href="/wiki/Hydrogen_bond" title="Hydrogen bond">hydrogen bonds</a> and salt-bridges. The C-terminal region also contains a <a href="/wiki/Low_density_lipoprotein_receptor" class="mw-redirect" title="Low density lipoprotein receptor">low density lipoprotein receptor</a> (LDLR)-binding site.<sup id="cite_ref-pmid25328986_18-0" class="reference"><a href="#cite_note-pmid25328986-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Polymorphisms">Polymorphisms</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=5" title="Edit section: Polymorphisms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output 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class="infobox"><tbody><tr><th colspan="2" class="infobox-above">SNP: rs429358</th></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Human_Genome_Organisation" title="Human Genome Organisation">Gene</a></th><td class="infobox-data"><a href="/wiki/ApoE" class="mw-redirect" title="ApoE">ApoE</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Chromosome" title="Chromosome">Chromosome</a></th><td class="infobox-data"><a href="/wiki/Chromosome_19" title="Chromosome 19">19</a></td></tr><tr><th colspan="2" class="infobox-header">External databases</th></tr><tr><td colspan="2" class="infobox-full-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1257001546"></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Ensembl" class="mw-redirect" title="Ensembl">Ensembl</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/snpview?source=dbSNP;snp=rs429358">Human SNPView</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/DbSNP" title="DbSNP">dbSNP</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs429358">429358</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/HapMap" class="mw-redirect" title="HapMap">HapMap</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="http://www.hapmap.org/cgi-perl/gbrowse/hapmap_B35/?name=SNP%3Ars429358">429358</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/SNPedia" title="SNPedia">SNPedia</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="https://www.snpedia.com/index.php?title=Rs429358">429358</a></td></tr><tr style="display:none"><td colspan="2"> </td></tr></tbody></table> <p><i>APOE</i> is <a href="/wiki/Gene_polymorphism" title="Gene polymorphism">polymorphic</a>,<sup id="cite_ref-pmid17092867_19-0" class="reference"><a href="#cite_note-pmid17092867-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-10.1002/ajpa.21298_20-0" class="reference"><a href="#cite_note-10.1002/ajpa.21298-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> with three major <a href="/wiki/Allele" title="Allele">alleles</a> (epsilon 2, epsilon 3, and epsilon 4): <i>APOE-ε2</i> (cys112, cys158), <i>APOE-ε3</i> (cys112, arg158), and <i>APOE-ε4</i> (arg112, arg158).<sup id="cite_ref-encyclopedia_5-1" class="reference"><a href="#cite_note-encyclopedia-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-cardiogenetics_21-0" class="reference"><a href="#cite_note-cardiogenetics-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid16603077_25-0" class="reference"><a href="#cite_note-pmid16603077-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> these differences alter APOE structure and function. </p><p>There are several low-frequency polymorphisms of APOE. APOE5 comes in two subtypes E5f and E5s, based on migration rates. APOE5 E5f and APOE7 combined were found in 2.8% of Japanese males.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)"><span title="Material near this tag may rely on an unreliable or less reliable medical source. Primary (December 2022)">unreliable medical source</span></a></i>]</sup> APOE7 is a mutation of APOE3 with two lysine residues replacing glutamic acid residues at positions 244 and 245.<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p> <table class="wikitable"> <tbody><tr> <th>Polymorphism </th> <th>Worldwide allele frequency </th> <th>Disease relevance </th></tr> <tr> <td>ε2 (rs7412-T, rs429358-T) </td> <td>8.4%<sup id="cite_ref-Liu2013_9-1" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </td> <td>This variant of the apoprotein binds poorly to cell surface receptors while E3 and E4 bind well.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> E2 is associated with both increased and decreased risk for <a href="/wiki/Atherosclerosis" title="Atherosclerosis">atherosclerosis</a>. Individuals with an E2/E2 combination may clear dietary fat slowly and be at greater risk for early vascular disease and the <a href="/wiki/Genetic_disorder" title="Genetic disorder">genetic disorder</a> <a href="/wiki/Type_III_hyperlipoproteinemia" class="mw-redirect" title="Type III hyperlipoproteinemia">type III hyperlipoproteinemia</a>—94.4% of people with such disease are E2/E2 but only ~2% of E2/E2 develop it, so other environmental and genetic factors are likely to be involved (such as cholesterol in the diet and age).<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> E2 has also been implicated in <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a>,<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> but this finding was not replicated in a larger population association study.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td>ε3 (rs7412-C, rs429358-T) </td> <td>77.9%<sup id="cite_ref-Liu2013_9-2" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </td> <td>This variant is considered the "neutral" <i>APOE</i> genotype. </td></tr> <tr> <td><span class="anchor" id="E4"></span>ε4 (rs7412-C, rs429358-C) </td> <td>13.7%<sup id="cite_ref-Liu2013_9-3" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </td> <td> <p>E4 has been implicated in <a href="/wiki/Atherosclerosis" title="Atherosclerosis">atherosclerosis</a>,<sup id="cite_ref-Phillips2014_34-0" class="reference"><a href="#cite_note-Phillips2014-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Mahley2000_35-0" class="reference"><a href="#cite_note-Mahley2000-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a>,<sup id="cite_ref-pmid8346443_36-0" class="reference"><a href="#cite_note-pmid8346443-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid8446617_37-0" class="reference"><a href="#cite_note-pmid8446617-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> impaired <a href="/wiki/Cognitive_function" class="mw-redirect" title="Cognitive function">cognitive function</a>,<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Cognitive_Impairment_39-0" class="reference"><a href="#cite_note-Cognitive_Impairment-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> reduced <a href="/wiki/Hippocampal" class="mw-redirect" title="Hippocampal">hippocampal</a> volume,<sup id="cite_ref-auto_40-0" class="reference"><a href="#cite_note-auto-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> <a href="/wiki/HIV" title="HIV">HIV</a>,<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> faster disease progression in <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>,<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> unfavorable outcome after <a href="/wiki/Traumatic_brain_injury" title="Traumatic brain injury">traumatic brain injury</a>,<sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> ischemic <a href="/wiki/Cerebrovascular_disease" title="Cerebrovascular disease">cerebrovascular disease</a>,<sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Sleep_apnea" title="Sleep apnea">sleep apnea</a>,<sup id="cite_ref-46" class="reference"><a href="#cite_note-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-47" class="reference"><a href="#cite_note-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> both the extension and shortening of <a href="/wiki/Telomere" title="Telomere">telomeres</a>,<sup id="cite_ref-pmid23418430_48-0" class="reference"><a href="#cite_note-pmid23418430-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Wikgren2012_49-0" class="reference"><a href="#cite_note-Wikgren2012-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Honig2006_50-0" class="reference"><a href="#cite_note-Honig2006-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Dhillon2020_51-0" class="reference"><a href="#cite_note-Dhillon2020-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> reduced <a href="/wiki/Neurite" title="Neurite">neurite</a> outgrowth,<sup id="cite_ref-pmid18395206_52-0" class="reference"><a href="#cite_note-pmid18395206-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/COVID-19" title="COVID-19">COVID-19</a>.<sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> However, E4 has also been associated with enhanced <a href="/wiki/Vitamin_D" title="Vitamin D">vitamin D</a> and <a href="/wiki/Calcium" title="Calcium">calcium</a> status,<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> higher <a href="/wiki/Fecundity" title="Fecundity">fecundity</a>,<sup id="cite_ref-55" class="reference"><a href="#cite_note-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> protection against early childhood <a href="/wiki/Infection" title="Infection">infection</a> and <a href="/wiki/Malnutrition" title="Malnutrition">malnutrition</a>,<sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup> and decreased <a href="/wiki/Fetal" class="mw-redirect" title="Fetal">fetal</a>, <a href="/wiki/Perinatal" class="mw-redirect" title="Perinatal">perinatal</a>, and <a href="/wiki/Infant" title="Infant">infant</a> mortality.<sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup> </p> </td></tr></tbody></table> <p>Much remains to be learned about the APOE isoforms, including the interaction of other protective genes.<sup id="cite_ref-Sundermann_EE_2016_58-0" class="reference"><a href="#cite_note-Sundermann_EE_2016-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup> Indeed, the apolipoprotein ε4 isoform is more protective against cognitive decline than other isoforms in some cases,<sup id="cite_ref-Sundermann_EE_2016_58-1" class="reference"><a href="#cite_note-Sundermann_EE_2016-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup> so caution is advised before making determinant statements about the influence of APOE polymorphisms on cognition, development of Alzheimer's disease, cardiovascular disease, telomere shortening, etc. Many of the studies cited that purport these adverse outcomes are from single studies that have not been replicated and the research is based on unchecked assumptions about this isoform. As of 2007, there was no evidence that APOE polymorphisms influence cognition in younger age groups (other than possible increased episodic memory ability and neural efficiency in younger APOE4 age groups), nor that the APOE4 isoform places individuals at increased risk for any infectious disease.<sup id="cite_ref-59" class="reference"><a href="#cite_note-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> </p><p>However, the association between the APOE4 allele and Alzheimer's disease has been shown to be weaker in minority groups differently compared to their Caucasian counterparts.<sup id="cite_ref-Liu2013_9-4" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Alzheimer%27s_disease_in_the_Hispanic/Latino_population" title="Alzheimer's disease in the Hispanic/Latino population">Hispanics/Latinos</a> and <a href="/wiki/Alzheimer%27s_disease_in_African_Americans" title="Alzheimer's disease in African Americans">African Americans</a> who were homozygous for the APOE4 allele had 2.2 and 5.7 times the odds, respectively of developing Alzheimer's disease.<sup id="cite_ref-:3_60-0" class="reference"><a href="#cite_note-:3-60"><span class="cite-bracket">[</span>60<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Liu2013_9-5" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> The APOE4 allele has an even stronger effect in <a href="/wiki/Alzheimer%27s_Disease_in_the_East_Asian_Population" class="mw-redirect" title="Alzheimer's Disease in the East Asian Population">East Asian populations</a>, with Japanese populations have 33 times the odds compared to other populations.<sup id="cite_ref-61" class="reference"><a href="#cite_note-61"><span class="cite-bracket">[</span>61<span class="cite-bracket">]</span></a></sup> Caucasians who were homozygous for the allele had 12.5 times the odds.<sup id="cite_ref-:3_60-1" class="reference"><a href="#cite_note-:3-60"><span class="cite-bracket">[</span>60<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Liu2013_9-6" class="reference"><a href="#cite_note-Liu2013-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Function">Function</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=6" title="Edit section: Function"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As a component of the lipoprotein lipid transport system, APOE facilitates the transport of <a href="/wiki/Lipid" title="Lipid">lipids</a>, fat-soluble <a href="/wiki/Vitamins" class="mw-redirect" title="Vitamins">vitamins</a>, and <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> via the blood. It interacts with the LDL receptor to facilitate endocytosis of VLDL remnants. It is synthesized principally in the <a href="/wiki/Liver" title="Liver">liver</a>, but has also been found in other tissues such as the <a href="/wiki/Brain" title="Brain">brain</a>, <a href="/wiki/Kidney" title="Kidney">kidneys</a>, and <a href="/wiki/Spleen" title="Spleen">spleen</a>.<sup id="cite_ref-cardiogenetics_21-1" class="reference"><a href="#cite_note-cardiogenetics-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> APOE synthesized in the liver associates with <a href="/wiki/High-density_lipoprotein" title="High-density lipoprotein">HDL</a> which can then distribute it to newly formed <a href="/wiki/VLDL" class="mw-redirect" title="VLDL">VLDL</a> or <a href="/wiki/Chylomicron" title="Chylomicron">chylomicron</a> particles to facilitate their eventual uptake by the liver. </p><p>In the nervous system, non-neuronal cell types, most notably <a href="/wiki/Astrocyte" title="Astrocyte">astroglia</a> and <a href="/wiki/Microglia" title="Microglia">microglia</a>, are the primary producers of APOE, while neurons preferentially express the receptors for APOE.<sup id="cite_ref-62" class="reference"><a href="#cite_note-62"><span class="cite-bracket">[</span>62<span class="cite-bracket">]</span></a></sup> There are seven currently identified mammalian <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptors</a> for APOE which belong to the evolutionarily conserved LDLR family.<sup id="cite_ref-63" class="reference"><a href="#cite_note-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> </p><p>APOE was initially recognized for its importance in lipoprotein <a href="/wiki/Metabolism" title="Metabolism">metabolism</a> and <a href="/wiki/Cardiovascular_disease" title="Cardiovascular disease">cardiovascular disease</a>. Defects in APOE result in <a href="/wiki/Familial_dysbetalipoproteinemia" title="Familial dysbetalipoproteinemia">familial dysbetalipoproteinemia</a> aka type III <a href="/wiki/Hyperlipoproteinemia" class="mw-redirect" title="Hyperlipoproteinemia">hyperlipoproteinemia</a> (HLP III), in which increased plasma <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> and triglycerides are the consequence of impaired clearance of <a href="/wiki/Chylomicron" title="Chylomicron">chylomicron</a>, <a href="/wiki/VLDL" class="mw-redirect" title="VLDL">VLDL</a> and <a href="/wiki/LDL" class="mw-redirect" title="LDL">LDL</a>.<sup id="cite_ref-Sacks_2015_64-0" class="reference"><a href="#cite_note-Sacks_2015-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-entrez_7-1" class="reference"><a href="#cite_note-entrez-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> More recently, it has been studied for its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease (AD), <a href="/wiki/Immune_system" title="Immune system">immunoregulation</a>, and <a href="/wiki/Cognition" title="Cognition">cognition</a>.<sup id="cite_ref-encyclopedia_5-2" class="reference"><a href="#cite_note-encyclopedia-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> Though the exact mechanisms remain to be elucidated, isoform 4 of APOE, encoded by an APOE allele, has been associated with increased calcium ion levels and apoptosis following mechanical injury.<sup id="cite_ref-65" class="reference"><a href="#cite_note-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> </p><p>In the field of immune regulation, a growing number of studies point to APOE's interaction with many immunological processes, including suppressing <a href="/wiki/T_cell" title="T cell">T cell</a> proliferation, <a href="/wiki/Macrophage" title="Macrophage">macrophage</a> functioning regulation, lipid antigen presentation facilitation (by <a href="/wiki/CD1" title="CD1">CD1</a>)<sup id="cite_ref-66" class="reference"><a href="#cite_note-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup> to <a href="/wiki/Natural_Killer_T_cell" class="mw-redirect" title="Natural Killer T cell">natural killer T cell</a> as well as modulation of <a href="/wiki/Inflammation" title="Inflammation">inflammation</a> and <a href="/wiki/Oxidation" class="mw-redirect" title="Oxidation">oxidation</a>.<sup id="cite_ref-pmid20182542_67-0" class="reference"><a href="#cite_note-pmid20182542-67"><span class="cite-bracket">[</span>67<span class="cite-bracket">]</span></a></sup> APOE is produced by macrophages and APOE secretion has been shown to be restricted to classical monocytes in PBMC, and the secretion of APOE by monocytes is down regulated by inflammatory cytokines and upregulated by TGF-beta.<sup id="cite_ref-pmid24244577_68-0" class="reference"><a href="#cite_note-pmid24244577-68"><span class="cite-bracket">[</span>68<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Clinical_significance">Clinical significance</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=7" title="Edit section: Clinical significance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Alzheimer's_disease"><span id="Alzheimer.27s_disease"></span>Alzheimer's disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=8" title="Edit section: Alzheimer's disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As of 2012, the E4 variant was the largest known genetic risk factor for late-onset sporadic <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a> (AD) in a variety of ethnic groups.<sup id="cite_ref-69" class="reference"><a href="#cite_note-69"><span class="cite-bracket">[</span>69<span class="cite-bracket">]</span></a></sup> However, the E4 variant does not correlate with risk in every population. Nigerian people have the highest observed frequency of the <i>APOE4</i> allele in world populations,<sup id="cite_ref-:0_70-0" class="reference"><a href="#cite_note-:0-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup> but AD is rare among them.<sup id="cite_ref-:0_70-1" class="reference"><a href="#cite_note-:0-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:1_71-0" class="reference"><a href="#cite_note-:1-71"><span class="cite-bracket">[</span>71<span class="cite-bracket">]</span></a></sup> This may be due to their low cholesterol levels.<sup id="cite_ref-:0_70-2" class="reference"><a href="#cite_note-:0-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:1_71-1" class="reference"><a href="#cite_note-:1-71"><span class="cite-bracket">[</span>71<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-72" class="reference"><a href="#cite_note-72"><span class="cite-bracket">[</span>72<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:2_73-0" class="reference"><a href="#cite_note-:2-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup> Caucasian and Japanese carriers of two E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, as compared to those not carrying any E4 alleles. This may be caused by an interaction with <a href="/wiki/Amyloid" title="Amyloid">amyloid</a>.<sup id="cite_ref-pmid1625800_74-0" class="reference"><a href="#cite_note-pmid1625800-74"><span class="cite-bracket">[</span>74<span class="cite-bracket">]</span></a></sup> Alzheimer's disease is characterized by build-ups of aggregates of the <a href="/wiki/Peptide" title="Peptide">peptide</a> <a href="/wiki/Beta-amyloid" class="mw-redirect" title="Beta-amyloid">beta-amyloid</a>. Apolipoprotein E enhances <a href="/wiki/Proteolytic" class="mw-redirect" title="Proteolytic">proteolytic</a> break-down of this peptide, both within and between cells. The <a href="/wiki/Isoform" class="mw-redirect" title="Isoform">isoform</a> APOE-ε4 is not as effective as the others at promoting these reactions, resulting in increased vulnerability to AD in individuals with that gene variation.<sup id="cite_ref-Neuron_75-0" class="reference"><a href="#cite_note-Neuron-75"><span class="cite-bracket">[</span>75<span class="cite-bracket">]</span></a></sup> </p><p>Recently, the amyloid hypothesis of Alzheimer's disease has been questioned, and an article in <i><a href="/wiki/Science_(journal)" title="Science (journal)">Science</a></i> claimed that "Just as removing smoke does not extinguish a fire, reducing amyloid plaques may not affect the course of Alzheimer's disease."<sup id="cite_ref-76" class="reference"><a href="#cite_note-76"><span class="cite-bracket">[</span>76<span class="cite-bracket">]</span></a></sup> The role that the E4 variant carries can still be fully explained even in the absence of a valid amyloid hypothesis given the fact that <a href="/wiki/Reelin" title="Reelin">reelin</a> signaling emerges to be one of the key processes involved in Alzheimer's disease<sup id="cite_ref-Relevance_of_a_Novel_Circuit-Level_77-0" class="reference"><a href="#cite_note-Relevance_of_a_Novel_Circuit-Level-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> and the E4 variant is shown to interact with <a href="/wiki/ApoER2" class="mw-redirect" title="ApoER2">ApoER2</a>, one of the neuronal reelin receptors, thereby obstructing reelin signaling.<sup id="cite_ref-Relevance_of_a_Novel_Circuit-Level_77-1" class="reference"><a href="#cite_note-Relevance_of_a_Novel_Circuit-Level-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> </p><p>Although 40–65% of AD patients have at least one copy of the ε4 allele, <i>APOE4</i> is not a determinant of the disease. At least one-third of patients with AD are <i>APOE4</i> negative and some <i>APOE4</i> homozygotes never develop the disease. Yet those with two ε4 alleles have up to 20 times the risk of developing AD.<sup id="cite_ref-HauserRyan2013_78-0" class="reference"><a href="#cite_note-HauserRyan2013-78"><span class="cite-bracket">[</span>78<span class="cite-bracket">]</span></a></sup> There is also evidence that the <i>APOE2</i> allele may serve a protective role in AD.<sup id="cite_ref-pmid7920638_79-0" class="reference"><a href="#cite_note-pmid7920638-79"><span class="cite-bracket">[</span>79<span class="cite-bracket">]</span></a></sup> Thus, the genotype most at risk for Alzheimer's disease and at an earlier age is APOE4,4. Using genotype APOE3,3 as a benchmark (with the persons who have this genotype regarded as having a risk level of 1.0) and for white populations only, individuals with genotype APOE4,4 have an <a href="/wiki/Odds_ratio" title="Odds ratio">odds ratio</a> of 14.9 of developing Alzheimer's disease. Individuals with the APOE3,4 genotype face an odds ratio of 3.2, and people with a copy of the 2 allele and the 4 allele (APOE2,4), have an odds ratio of 2.6. Persons with one copy each of the 2 allele and the 3 allele (APOE2,3) have an odds ratio of 0.6. Persons with two copies of the 2 allele (APOE2,2) also have an odds ratio of 0.6.<sup id="cite_ref-Farrer1997_80-0" class="reference"><a href="#cite_note-Farrer1997-80"><span class="cite-bracket">[</span>80<span class="cite-bracket">]</span></a></sup> </p> <table class="wikitable"> <tbody><tr> <td colspan="5" align="center" style="color: black; background: #ccccff"><b>Estimated worldwide human allele frequencies of APOE</b> in Caucasian population<sup id="cite_ref-Farrer1997_80-1" class="reference"><a href="#cite_note-Farrer1997-80"><span class="cite-bracket">[</span>80<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <th align="center" style="color: black; background: #ccccff">Allele </th> <th align="center" style="color: black; background: #ccccff">ε2 </th> <th align="center" style="color: black; background: #ccccff">ε3 </th> <th align="center" style="color: black; background: #ccccff">ε4 </th></tr> <tr> <td align="center" style="color: black; background: #ccccff">General frequency </td> <td align="center">8.4% </td> <td align="center">77.9% </td> <td align="center">13.7% </td></tr> <tr> <td align="center" style="color: black; background: #ccccff">AD frequency </td> <td align="center">3.9% </td> <td align="center">59.4% </td> <td align="center">36.7% </td></tr></tbody></table> <p>While ApoE4 has been found to greatly increase the odds that an individual will develop Alzheimer's, a 2002 study concluded, that in persons with any combination of APOE alleles, high serum total cholesterol and high blood pressure in mid-life are independent risk factors which together can nearly triple the risk that the individual will later develop AD.<sup id="cite_ref-:2_73-1" class="reference"><a href="#cite_note-:2-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup> Projecting from their data, some researchers have suggested that lowering serum cholesterol levels may reduce a person's risk for Alzheimer's disease, even if they have two ApoE4 alleles, thus reducing the risk from nine or ten times the odds of getting AD down to just two times the odds.<sup id="cite_ref-:2_73-2" class="reference"><a href="#cite_note-:2-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup> </p><p>Women are more likely to develop AD than men across most ages and APOE genotypes. Premorbid women with the ε4 allele have significantly more neurological dysfunction than men.<sup id="cite_ref-81" class="reference"><a href="#cite_note-81"><span class="cite-bracket">[</span>81<span class="cite-bracket">]</span></a></sup> </p><p><i>APOE-ε4</i> increases the risk not only for AD but also for dementia in pure alpha-synucleinopathies.<sup id="cite_ref-82" class="reference"><a href="#cite_note-82"><span class="cite-bracket">[</span>82<span class="cite-bracket">]</span></a></sup> The influence of <i>APOE</i>-ε4 on hippocampal atrophy was suggested to be more predominant early in the course of AD at milder stages prior to more widespread neurodegeneration.<sup id="cite_ref-auto_40-1" class="reference"><a href="#cite_note-auto-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p><p>With the approval of the first disease-modifying therapies for AD based on monoclonal antibodies against amyloid-beta, which delay disease progression, APOE genotyping has also become important in assessing a patient’s risk of side effects under therapy. In November 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended the marketing authorisation of lecanemab (anti-beta-amyloid antibody; trade name: Leqembi® from Eisai and Biogen) in Europe for the treatment of adult patients diagnosed with early-stage AD (mild cognitive impairment and mild dementia) who have no or only one copy of the APOE-ε4 allele.<sup id="cite_ref-83" class="reference"><a href="#cite_note-83"><span class="cite-bracket">[</span>83<span class="cite-bracket">]</span></a></sup> </p><p>As homozygous carriers of APOE-ɛ4 have the highest risk of all APOE genotypes of developing potentially life-threatening side effects (called amyloid-related imaging abnormalities, ARIA) under treatment, this APOE genotype was excluded in the indication of Leqembi®.<sup id="cite_ref-84" class="reference"><a href="#cite_note-84"><span class="cite-bracket">[</span>84<span class="cite-bracket">]</span></a></sup> Therefore, detection of the APOE gene variant is recommended prior to starting anti-beta-amyloid therapy to assess the patient’s risk of adverse effects.<sup id="cite_ref-85" class="reference"><a href="#cite_note-85"><span class="cite-bracket">[</span>85<span class="cite-bracket">]</span></a></sup> </p><p>The APOE genotyping of AD patients for risk assessment in the context of an anti-beta-amyloid therapy can be performed with the help of commercially available PCR-based assays.<sup id="cite_ref-86" class="reference"><a href="#cite_note-86"><span class="cite-bracket">[</span>86<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Atherosclerosis">Atherosclerosis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=9" title="Edit section: Atherosclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Knockout_mouse" title="Knockout mouse">Knockout mice</a> that lack the apolipoprotein-E gene (APOE<sup>−/−</sup>) develop extreme <a href="/wiki/Hypercholesterolemia" title="Hypercholesterolemia">hypercholesterolemia</a> when fed a high-fat diet.<sup id="cite_ref-pmid20210786_87-0" class="reference"><a href="#cite_note-pmid20210786-87"><span class="cite-bracket">[</span>87<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Malaria">Malaria</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=10" title="Edit section: Malaria"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>APOE<sup>−/−</sup> knockout mice show marked attenuation of cerebral <a href="/wiki/Malaria" title="Malaria">malaria</a> and increased survival, as well as decreased sequestration of parasites and T cells within the brain, likely due to protection of the <a href="/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier">blood–brain barrier</a>.<sup id="cite_ref-pmid27647324_88-0" class="reference"><a href="#cite_note-pmid27647324-88"><span class="cite-bracket">[</span>88<span class="cite-bracket">]</span></a></sup> Human studies have shown that the APOE2 polymorphism correlates with earlier infection, and APOE3/4 polymorphisms increase likelihood of severe malaria.<sup id="cite_ref-pmid14985370_89-0" class="reference"><a href="#cite_note-pmid14985370-89"><span class="cite-bracket">[</span>89<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Lyme_disease">Lyme disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=11" title="Edit section: Lyme disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i>Borrelia burgdorferi</i>, the causative agent of <a href="/wiki/Lyme_disease" title="Lyme disease">Lyme disease</a>, is a host-adapted pathogen that acquires environmental cholesterol to form glycolipids for use in cell membrane maintenance. In one <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25870274/">experiment</a> in 2015, mice engineered with apoE deficiency were infected with <i>Borrelia</i> spirochetes. The knockout mice suffered from an increased spirochete burden in joints, as well as inflamed ankles, when compared with wild-type mice. This study suggests that apoE deficiency (and potentially other hyperlipidemias) may be a risk factor in the pathogenicity of Lyme disease. </p> <div class="mw-heading mw-heading2"><h2 id="Interactions">Interactions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=12" title="Edit section: Interactions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Interactive_pathway_map">Interactive pathway map</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=13" title="Edit section: Interactive pathway map"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i>Click on genes, proteins and metabolites below to link to respective articles.</i> <sup id="cite_ref-WikiPathways_90-0" class="reference"><a href="#cite_note-WikiPathways-90"><span class="cite-bracket">[</span>§ 1<span class="cite-bracket">]</span></a></sup> </p> <div style="overflow:auto;"> <div class="thumb tleft"> <div class="thumbinner" style="width: 377px;"> <div class="thumbimage" style="width: 375px; height: 350px; overflow: hidden;"> <div style="position: relative; top: -259.8px; left: -461.2px; width: px"><div class="noresize">[[File:<div class="noresize thumb tnone" style=";"> <div class="thumbinner" style="overflow:hidden;width:830px;"> <div class="thumbimage" style="overflow:hidden; position:relative; background-color:white;"> <div style=";left:0px; top:0px; width:828px; position:absolute;"> <figure class="mw-default-size mw-halign-right noresize" typeof="mw:File"><a href="/wiki/Statin#Other_effects" title="Go to pathway article"><img alt="Statin_Pathway_WP430" src="//upload.wikimedia.org/wikipedia/commons/f/f6/StatinPathway_WP430.png" decoding="async" width="828" height="743" class="mw-file-element" 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article" /><area href="/wiki/ABCG5" shape="rect" coords="125,555,185,575" alt="go to article" title="go to article" /><area href="/wiki/ABCG8" shape="rect" coords="125,575,185,595" alt="go to article" title="go to article" /><area href="/wiki/ABCA1" shape="rect" coords="413,605,473,625" alt="go to article" title="go to article" /><area href="/wiki/Cholesterol" shape="rect" coords="509,622,577,641" alt="go to article" title="go to article" /><area href="/wiki/Apolipoprotein_B" shape="rect" coords="609,440,669,460" alt="go to article" title="go to article" /><area href="/wiki/APOA5" shape="rect" coords="669,440,729,460" alt="go to article" title="go to article" /><area href="/wiki/Microsomal_triglyceride_transfer_protein" shape="rect" coords="572,314,621,334" alt="go to article" title="go to article" /><area href="/wiki/Diglyceride" shape="rect" coords="583,96,629,116" alt="go to article" title="go to article" /><area href="/wiki/Squalene" shape="rect" coords="127,218,194,238" alt="go to article" title="go to article" /><area href="/wiki/Farnesyl-diphosphate_farnesyltransferase" shape="rect" coords="40,245,91,265" alt="go to article" title="go to article" /><area href="/wiki/Squalene_monooxygenase" shape="rect" coords="202,181,245,201" alt="go to article" title="go to article" /><area href="/wiki/Acyl-CoA" shape="rect" coords="498,114,552,134" alt="go to article" title="go to article" /><area href="/wiki/Acyl-CoA_synthetase" shape="rect" coords="431,76,533,96" alt="go to article" title="go to article" /><area href="/wiki/Protein_disulfide-isomerase" shape="rect" coords="572,294,621,314" alt="go to article" title="go to article" /><area href="/wiki/Cholesterol" shape="rect" coords="359,541,428,560" alt="go to article" title="go to article" /><area href="/wiki/APOA2" shape="rect" coords="522,471,582,491" alt="go to article" title="go to article" /><area href="/wiki/MiR-33" shape="rect" coords="348,666,428,686" alt="go to article" title="go to article" /><area href="/wiki/MiR-33" shape="rect" coords="348,686,428,706" alt="go to article" title="go to article" /></map><figcaption></figcaption></figure></div> </div> <div class="thumbcaption"></div> </div></div>|alt=Statin pathway <a rel="nofollow" class="external text" href="http://www.wikipathways.org/index.php/Pathway:WP430">edit</a>]]</div></div> </div> <div class="thumbcaption"> <div class="magnify"><a href="/wiki/File:StatinPathway_WP430.png" title="File:StatinPathway WP430.png"> </a></div>Statin pathway <a rel="nofollow" class="external text" href="http://www.wikipathways.org/index.php/Pathway:WP430">edit</a> </div> </div> </div> <div style="clear:both;" class=""></div><style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap"><ol class="references"> <li id="cite_note-WikiPathways-90"><span class="mw-cite-backlink"><b><a href="#cite_ref-WikiPathways_90-0">^</a></b></span> <span class="reference-text">The interactive pathway map can be edited at WikiPathways: <style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.wikipathways.org/index.php/Pathway:WP430">"Statin_Pathway_WP430"</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Statin_Pathway_WP430&rft_id=http%3A%2F%2Fwww.wikipathways.org%2Findex.php%2FPathway%3AWP430&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></span> </li> </ol></div></div> </div> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=14" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239543626"><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-refGRCh38Ensembl-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-refGRCh38Ensembl_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><a rel="nofollow" class="external text" href="http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000130203">GRCh38: Ensembl release 89: ENSG00000130203</a> – <a href="/wiki/Ensembl_genome_database_project" title="Ensembl genome database project">Ensembl</a>, May 2017</span> </li> <li id="cite_note-refGRCm38Ensembl-2"><span class="mw-cite-backlink">^ <a href="#cite_ref-refGRCm38Ensembl_2-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-refGRCm38Ensembl_2-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-refGRCm38Ensembl_2-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><a rel="nofollow" class="external text" href="http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000002985">GRCm38: Ensembl release 89: ENSMUSG00000002985</a> – <a href="/wiki/Ensembl_genome_database_project" title="Ensembl genome database project">Ensembl</a>, May 2017</span> </li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="#cite_ref-3">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=348">"Human PubMed Reference:"</a>. <i>National Center for Biotechnology Information, U.S. National Library of Medicine</i>.</cite><span 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href="https://doi.org/10.1101%2F2020.06.18.159632">10.1101/2020.06.18.159632</a></span>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1073%2Fpnas.2102191118">10.1073/pnas.2102191118</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379952">8379952</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/34385305">34385305</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" 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class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFWozniakRileyItzhaki2004" class="citation journal cs1">Wozniak MA, Riley EM, Itzhaki RF (March 2004). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735716">"Apolipoprotein E polymorphisms and risk of malaria"</a>. <i>Journal of Medical Genetics</i>. <b>41</b> (3): <span class="nowrap">145–</span>146. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1136%2Fjmg.2003.014613">10.1136/jmg.2003.014613</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735716">1735716</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/14985370">14985370</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Medical+Genetics&rft.atitle=Apolipoprotein+E+polymorphisms+and+risk+of+malaria&rft.volume=41&rft.issue=3&rft.pages=%3Cspan+class%3D%22nowrap%22%3E145-%3C%2Fspan%3E146&rft.date=2004-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1735716%23id-name%3DPMC&rft_id=info%3Apmid%2F14985370&rft_id=info%3Adoi%2F10.1136%2Fjmg.2003.014613&rft.aulast=Wozniak&rft.aufirst=MA&rft.au=Riley%2C+EM&rft.au=Itzhaki%2C+RF&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1735716&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></span> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Apolipoprotein_E&action=edit&section=15" title="Edit section: Further reading"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239549316">.mw-parser-output .refbegin{margin-bottom:0.5em}.mw-parser-output .refbegin-hanging-indents>ul{margin-left:0}.mw-parser-output .refbegin-hanging-indents>ul>li{margin-left:0;padding-left:3.2em;text-indent:-3.2em}.mw-parser-output .refbegin-hanging-indents ul,.mw-parser-output .refbegin-hanging-indents ul li{list-style:none}@media(max-width:720px){.mw-parser-output .refbegin-hanging-indents>ul>li{padding-left:1.6em;text-indent:-1.6em}}.mw-parser-output .refbegin-columns{margin-top:0.3em}.mw-parser-output .refbegin-columns ul{margin-top:0}.mw-parser-output .refbegin-columns li{page-break-inside:avoid;break-inside:avoid-column}@media screen{.mw-parser-output .refbegin{font-size:90%}}</style><div class="refbegin refbegin-columns references-column-width" style="column-width: 30em"> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAshford2004" class="citation journal cs1">Ashford JW (2004). "APOE genotype effects on Alzheimer's disease onset and epidemiology". <i>Journal of Molecular Neuroscience</i>. <b>23</b> (3): <span class="nowrap">157–</span>165. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1385%2FJMN%3A23%3A3%3A157">10.1385/JMN:23:3:157</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15181244">15181244</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:14864342">14864342</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Neuroscience&rft.atitle=APOE+genotype+effects+on+Alzheimer%27s+disease+onset+and+epidemiology&rft.volume=23&rft.issue=3&rft.pages=%3Cspan+class%3D%22nowrap%22%3E157-%3C%2Fspan%3E165&rft.date=2004&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A14864342%23id-name%3DS2CID&rft_id=info%3Apmid%2F15181244&rft_id=info%3Adoi%2F10.1385%2FJMN%3A23%3A3%3A157&rft.aulast=Ashford&rft.aufirst=JW&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBeffertDanikKrzywkowskiRamassamy1998" class="citation journal cs1">Beffert U, Danik M, Krzywkowski P, Ramassamy C, Berrada F, Poirier J (July 1998). "The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer's disease". <i>Brain Research. Brain Research Reviews</i>. <b>27</b> (2): <span class="nowrap">119–</span>142. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0165-0173%2898%2900008-3">10.1016/S0165-0173(98)00008-3</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/9622609">9622609</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:28731779">28731779</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Brain+Research.+Brain+Research+Reviews&rft.atitle=The+neurobiology+of+apolipoproteins+and+their+receptors+in+the+CNS+and+Alzheimer%27s+disease&rft.volume=27&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E119-%3C%2Fspan%3E142&rft.date=1998-07&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A28731779%23id-name%3DS2CID&rft_id=info%3Apmid%2F9622609&rft_id=info%3Adoi%2F10.1016%2FS0165-0173%2898%2900008-3&rft.aulast=Beffert&rft.aufirst=U&rft.au=Danik%2C+M&rft.au=Krzywkowski%2C+P&rft.au=Ramassamy%2C+C&rft.au=Berrada%2C+F&rft.au=Poirier%2C+J&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBennetDi_AngelantonioYeWensley2007" class="citation journal cs1">Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, et al. (September 2007). "Association of apolipoprotein E genotypes with lipid levels and coronary risk". <i>JAMA</i>. <b>298</b> (11): <span class="nowrap">1300–</span>1311. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1001%2Fjama.298.11.1300">10.1001/jama.298.11.1300</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17878422">17878422</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Association+of+apolipoprotein+E+genotypes+with+lipid+levels+and+coronary+risk&rft.volume=298&rft.issue=11&rft.pages=%3Cspan+class%3D%22nowrap%22%3E1300-%3C%2Fspan%3E1311&rft.date=2007-09&rft_id=info%3Adoi%2F10.1001%2Fjama.298.11.1300&rft_id=info%3Apmid%2F17878422&rft.aulast=Bennet&rft.aufirst=AM&rft.au=Di+Angelantonio%2C+E&rft.au=Ye%2C+Z&rft.au=Wensley%2C+F&rft.au=Dahlin%2C+A&rft.au=Ahlbom%2C+A&rft.au=Keavney%2C+B&rft.au=Collins%2C+R&rft.au=Wiman%2C+B&rft.au=de+Faire%2C+U&rft.au=Danesh%2C+J&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBockschStephensLucasSingh2001" class="citation journal cs1">Bocksch L, Stephens T, Lucas A, Singh B (December 2001). "Apolipoprotein E: possible therapeutic target for atherosclerosis". <i>Current Drug Targets. Cardiovascular & Hematological Disorders</i>. <b>1</b> (2): <span class="nowrap">93–</span>106. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.2174%2F1568006013337944">10.2174/1568006013337944</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12769659">12769659</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Current+Drug+Targets.+Cardiovascular+%26+Hematological+Disorders&rft.atitle=Apolipoprotein+E%3A+possible+therapeutic+target+for+atherosclerosis&rft.volume=1&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E93-%3C%2Fspan%3E106&rft.date=2001-12&rft_id=info%3Adoi%2F10.2174%2F1568006013337944&rft_id=info%3Apmid%2F12769659&rft.aulast=Bocksch&rft.aufirst=L&rft.au=Stephens%2C+T&rft.au=Lucas%2C+A&rft.au=Singh%2C+B&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFde_Knijffvan_den_MaagdenbergFrantsHavekes1995" class="citation journal cs1">de Knijff P, van den Maagdenberg AM, Frants RR, Havekes LM (1995). <a rel="nofollow" class="external text" href="https://doi.org/10.1002%2Fhumu.1380040303">"Genetic heterogeneity of apolipoprotein E and its influence on plasma lipid and lipoprotein levels"</a>. <i>Human Mutation</i>. <b>4</b> (3): <span class="nowrap">178–</span>194. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1002%2Fhumu.1380040303">10.1002/humu.1380040303</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/7833947">7833947</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:41959843">41959843</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Human+Mutation&rft.atitle=Genetic+heterogeneity+of+apolipoprotein+E+and+its+influence+on+plasma+lipid+and+lipoprotein+levels&rft.volume=4&rft.issue=3&rft.pages=%3Cspan+class%3D%22nowrap%22%3E178-%3C%2Fspan%3E194&rft.date=1995&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A41959843%23id-name%3DS2CID&rft_id=info%3Apmid%2F7833947&rft_id=info%3Adoi%2F10.1002%2Fhumu.1380040303&rft.aulast=de+Knijff&rft.aufirst=P&rft.au=van+den+Maagdenberg%2C+AM&rft.au=Frants%2C+RR&rft.au=Havekes%2C+LM&rft_id=https%3A%2F%2Fdoi.org%2F10.1002%252Fhumu.1380040303&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGunzburgPeruginiHowlett2007" class="citation journal cs1">Gunzburg MJ, Perugini MA, Howlett GJ (December 2007). <a rel="nofollow" class="external text" href="https://doi.org/10.1074%2Fjbc.M706425200">"Structural basis for the recognition and cross-linking of amyloid fibrils by human apolipoprotein E"</a>. <i>The Journal of Biological Chemistry</i>. <b>282</b> (49): <span class="nowrap">35831–</span>35841. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1074%2Fjbc.M706425200">10.1074/jbc.M706425200</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17916554">17916554</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+Biological+Chemistry&rft.atitle=Structural+basis+for+the+recognition+and+cross-linking+of+amyloid+fibrils+by+human+apolipoprotein+E&rft.volume=282&rft.issue=49&rft.pages=%3Cspan+class%3D%22nowrap%22%3E35831-%3C%2Fspan%3E35841&rft.date=2007-12&rft_id=info%3Adoi%2F10.1074%2Fjbc.M706425200&rft_id=info%3Apmid%2F17916554&rft.aulast=Gunzburg&rft.aufirst=MJ&rft.au=Perugini%2C+MA&rft.au=Howlett%2C+GJ&rft_id=https%3A%2F%2Fdoi.org%2F10.1074%252Fjbc.M706425200&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHuangWeisgraberMuckeMahley2004" class="citation journal cs1">Huang Y, Weisgraber KH, Mucke L, Mahley RW (2004). "Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease". <i>Journal of Molecular Neuroscience</i>. <b>23</b> (3): <span class="nowrap">189–</span>204. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1385%2FJMN%3A23%3A3%3A189">10.1385/JMN:23:3:189</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15181247">15181247</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:40135107">40135107</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Neuroscience&rft.atitle=Apolipoprotein+E%3A+diversity+of+cellular+origins%2C+structural+and+biophysical+properties%2C+and+effects+in+Alzheimer%27s+disease&rft.volume=23&rft.issue=3&rft.pages=%3Cspan+class%3D%22nowrap%22%3E189-%3C%2Fspan%3E204&rft.date=2004&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A40135107%23id-name%3DS2CID&rft_id=info%3Apmid%2F15181247&rft_id=info%3Adoi%2F10.1385%2FJMN%3A23%3A3%3A189&rft.aulast=Huang&rft.aufirst=Y&rft.au=Weisgraber%2C+KH&rft.au=Mucke%2C+L&rft.au=Mahley%2C+RW&rfr_id=info%3Asid%2Fen.wikipedia.org%3AApolipoprotein+E" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFItzhakiDobsonShipleyWozniak2004" class="citation journal cs1">Itzhaki RF, Dobson CB, Shipley SJ, Wozniak MA (June 2004). 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rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=Apolipoproteins+E">Apolipoproteins+E</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li> <li><a rel="nofollow" class="external text" href="http://apoe4.info">apoe4.info – website for APOE-epsilon-4 carriers</a></li> <li>Human <a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=APOE"><i>APOE</i></a> genome location and <a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=APOE"><i>APOE</i></a> gene details page in the <a href="/wiki/UCSC_Genome_Browser" title="UCSC Genome Browser">UCSC Genome Browser</a>.</li> <li>Overview of all the structural information available in the <a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a> for <a href="/wiki/UniProt" title="UniProt">UniProt</a>: <i><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P02649">P02649</a></i> (Apolipoprotein E) at the <a href="/wiki/PDBe-KB" title="PDBe-KB">PDBe-KB</a>.</li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl ol,.mw-parser-output .hlist dl ul,.mw-parser-output .hlist ol dl,.mw-parser-output .hlist ol ol,.mw-parser-output .hlist ol ul,.mw-parser-output .hlist ul dl,.mw-parser-output .hlist ul ol,.mw-parser-output .hlist ul ul{display:inline}.mw-parser-output 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title="Special:EditPage/Template:PDB Gallery"><abbr title="Edit this template" style="color:inherit">e</abbr></a></li></ul></div><div id="PDB_gallery11" style="font-size:114%;margin:0 4em">PDB gallery</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><ul class="gallery mw-gallery-traditional nochecker" style="line-height:130%"> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1b68_EBI.jpg" class="mw-file-description" title="1b68: APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT"><img alt="1b68: APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT" src="//upload.wikimedia.org/wikipedia/commons/thumb/1/17/PDB_1b68_EBI.jpg/180px-PDB_1b68_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/17/PDB_1b68_EBI.jpg/270px-PDB_1b68_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/17/PDB_1b68_EBI.jpg/360px-PDB_1b68_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1b68</b>: APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1bz4_EBI.jpg" class="mw-file-description" title="1bz4: APOLIPOPROTEIN E3 (APO-E3), TRUNCATION MUTANT 165"><img alt="1bz4: APOLIPOPROTEIN E3 (APO-E3), TRUNCATION MUTANT 165" src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f4/PDB_1bz4_EBI.jpg/180px-PDB_1bz4_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f4/PDB_1bz4_EBI.jpg/270px-PDB_1bz4_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f4/PDB_1bz4_EBI.jpg/360px-PDB_1bz4_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1bz4</b>: APOLIPOPROTEIN E3 (APO-E3), TRUNCATION MUTANT 165</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1ea8_EBI.jpg" class="mw-file-description" title="1ea8: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLU MUTANT"><img alt="1ea8: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLU MUTANT" src="//upload.wikimedia.org/wikipedia/commons/thumb/3/30/PDB_1ea8_EBI.jpg/180px-PDB_1ea8_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/30/PDB_1ea8_EBI.jpg/270px-PDB_1ea8_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/30/PDB_1ea8_EBI.jpg/360px-PDB_1ea8_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1ea8</b>: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLU MUTANT</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1gs9_EBI.jpg" class="mw-file-description" title="1gs9: APOLIPOPROTEIN E4, 22K DOMAIN"><img alt="1gs9: APOLIPOPROTEIN E4, 22K DOMAIN" src="//upload.wikimedia.org/wikipedia/commons/thumb/1/10/PDB_1gs9_EBI.jpg/180px-PDB_1gs9_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/10/PDB_1gs9_EBI.jpg/270px-PDB_1gs9_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/10/PDB_1gs9_EBI.jpg/360px-PDB_1gs9_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1gs9</b>: APOLIPOPROTEIN E4, 22K DOMAIN</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1h7i_EBI.jpg" class="mw-file-description" title="1h7i: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLN MUTANT"><img alt="1h7i: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLN MUTANT" src="//upload.wikimedia.org/wikipedia/commons/thumb/1/13/PDB_1h7i_EBI.jpg/180px-PDB_1h7i_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/13/PDB_1h7i_EBI.jpg/270px-PDB_1h7i_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/13/PDB_1h7i_EBI.jpg/360px-PDB_1h7i_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1h7i</b>: APOLIPOPROTEIN E3 22KD FRAGMENT LYS146GLN MUTANT</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1le2_EBI.jpg" class="mw-file-description" title="1le2: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E"><img alt="1le2: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E" src="//upload.wikimedia.org/wikipedia/commons/thumb/b/bd/PDB_1le2_EBI.jpg/180px-PDB_1le2_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/bd/PDB_1le2_EBI.jpg/270px-PDB_1le2_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/bd/PDB_1le2_EBI.jpg/360px-PDB_1le2_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1le2</b>: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1le4_EBI.jpg" class="mw-file-description" title="1le4: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E"><img alt="1le4: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E" src="//upload.wikimedia.org/wikipedia/commons/thumb/3/33/PDB_1le4_EBI.jpg/180px-PDB_1le4_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/33/PDB_1le4_EBI.jpg/270px-PDB_1le4_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/33/PDB_1le4_EBI.jpg/360px-PDB_1le4_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1le4</b>: STRUCTURAL BASIS FOR ALTERED FUNCTION IN THE COMMON MUTANTS OF HUMAN APOLIPOPROTEIN-E</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1lpe_EBI.jpg" class="mw-file-description" title="1lpe: THREE-DIMENSIONAL STRUCTURE OF THE LDL RECEPTOR-BINDING DOMAIN OF HUMAN APOLIPOPROTEIN E"><img alt="1lpe: THREE-DIMENSIONAL STRUCTURE OF THE LDL RECEPTOR-BINDING DOMAIN OF HUMAN APOLIPOPROTEIN E" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a5/PDB_1lpe_EBI.jpg/180px-PDB_1lpe_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a5/PDB_1lpe_EBI.jpg/270px-PDB_1lpe_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a5/PDB_1lpe_EBI.jpg/360px-PDB_1lpe_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1lpe</b>: THREE-DIMENSIONAL STRUCTURE OF THE LDL RECEPTOR-BINDING DOMAIN OF HUMAN APOLIPOPROTEIN E</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1nfn_EBI.jpg" class="mw-file-description" title="1nfn: APOLIPOPROTEIN E3 (APOE3)"><img alt="1nfn: APOLIPOPROTEIN E3 (APOE3)" src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c6/PDB_1nfn_EBI.jpg/180px-PDB_1nfn_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/c6/PDB_1nfn_EBI.jpg/270px-PDB_1nfn_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/c6/PDB_1nfn_EBI.jpg/360px-PDB_1nfn_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1nfn</b>: APOLIPOPROTEIN E3 (APOE3)</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1nfo_EBI.jpg" class="mw-file-description" title="1nfo: APOLIPOPROTEIN E2 (APOE2, D154A MUTATION)"><img alt="1nfo: APOLIPOPROTEIN E2 (APOE2, D154A MUTATION)" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/PDB_1nfo_EBI.jpg/180px-PDB_1nfo_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/PDB_1nfo_EBI.jpg/270px-PDB_1nfo_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d6/PDB_1nfo_EBI.jpg/360px-PDB_1nfo_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1nfo</b>: APOLIPOPROTEIN E2 (APOE2, D154A MUTATION)</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1or2_EBI.jpg" class="mw-file-description" title="1or2: APOLIPOPROTEIN E3 (APOE3) TRUNCATION MUTANT 165"><img alt="1or2: APOLIPOPROTEIN E3 (APOE3) TRUNCATION MUTANT 165" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/ad/PDB_1or2_EBI.jpg/180px-PDB_1or2_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/ad/PDB_1or2_EBI.jpg/270px-PDB_1or2_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/ad/PDB_1or2_EBI.jpg/360px-PDB_1or2_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1or2</b>: APOLIPOPROTEIN E3 (APOE3) TRUNCATION MUTANT 165</div> </li> <li class="gallerybox" style="width: 215px"> <div class="thumb" style="width: 210px; height: 210px;"><span typeof="mw:File"><a href="/wiki/File:PDB_1or3_EBI.jpg" class="mw-file-description" title="1or3: APOLIPOPROTEIN E3 (APOE3), TRIGONAL TRUNCATION MUTANT 165"><img alt="1or3: APOLIPOPROTEIN E3 (APOE3), TRIGONAL TRUNCATION MUTANT 165" src="//upload.wikimedia.org/wikipedia/commons/thumb/e/eb/PDB_1or3_EBI.jpg/180px-PDB_1or3_EBI.jpg" decoding="async" width="180" height="135" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/eb/PDB_1or3_EBI.jpg/270px-PDB_1or3_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/eb/PDB_1or3_EBI.jpg/360px-PDB_1or3_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span></div> <div class="gallerytext"><b>1or3</b>: APOLIPOPROTEIN E3 (APOE3), TRIGONAL TRUNCATION MUTANT 165</div> </li> </ul></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Lipids:_lipoprotein_particle_metabolism298" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="3"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Lipoprotein_metabolism" title="Template:Lipoprotein metabolism"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Lipoprotein_metabolism" title="Template talk:Lipoprotein metabolism"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Lipoprotein_metabolism" title="Special:EditPage/Template:Lipoprotein metabolism"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Lipids:_lipoprotein_particle_metabolism298" style="font-size:114%;margin:0 4em"><a href="/wiki/Lipid" title="Lipid">Lipids</a>: <a href="/wiki/Lipoprotein" title="Lipoprotein">lipoprotein</a> particle metabolism</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Lipoprotein" title="Lipoprotein">Lipoprotein</a> particle classes<br /> and subclasses</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>delivery of <a href="/wiki/Triglyceride" title="Triglyceride">TGs</a>: <a href="/wiki/Chylomicron" title="Chylomicron">Chylomicron</a></li> <li><a href="/wiki/Very_low-density_lipoprotein" title="Very low-density lipoprotein">VLDL</a></li> <li>delivery of <a href="/wiki/Cholesterol" title="Cholesterol">C</a> and <a href="/wiki/Cholesteryl_ester" title="Cholesteryl ester">CE</a>: <a href="/wiki/Intermediate-density_lipoprotein" title="Intermediate-density lipoprotein">IDL</a></li> <li><a href="/wiki/Low-density_lipoprotein" title="Low-density lipoprotein">LDL</a></li> <li>lb LDL</li> <li>sd LDL</li> <li><a href="/wiki/Lipoprotein(a)" title="Lipoprotein(a)">Lp(a)</a></li> <li><a href="/wiki/High-density_lipoprotein" title="High-density lipoprotein">HDL</a></li> <li><a href="/wiki/Remnant_cholesterol" title="Remnant cholesterol">Remnant cholesterol</a></li></ul> </div></td><td class="noviewer navbox-image" rowspan="6" style="width:1px;padding:0 0 0 2px"><div><span typeof="mw:File"><a href="/wiki/File:2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/ab/2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg/350px-2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg" decoding="async" width="350" height="280" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/ab/2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg/525px-2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/ab/2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg/700px-2512_Chylomicrons_Contain_Triglycerides_Cholesterol_Molecules_and_Other_Lipids.jpg 2x" data-file-width="1228" data-file-height="981" /></a></span></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Apolipoprotein" title="Apolipoprotein">Apolipoproteins</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>APOA <ul><li><a href="/wiki/Apolipoprotein_AI" title="Apolipoprotein AI">1</a></li> <li><a href="/wiki/APOA2" class="mw-redirect" title="APOA2">2</a></li> <li><a href="/wiki/APOA4" title="APOA4">4</a></li> <li><a href="/wiki/APOA5" title="APOA5">5</a></li></ul></li> <li><a href="/wiki/Apolipoprotein_B" title="Apolipoprotein B">APOB</a></li> <li>APOC <ul><li><a href="/wiki/Apolipoprotein_C1" class="mw-redirect" title="Apolipoprotein C1">1</a></li> <li><a href="/wiki/Apolipoprotein_C2" class="mw-redirect" title="Apolipoprotein C2">2</a></li> <li><a href="/wiki/Apolipoprotein_C3" class="mw-redirect" title="Apolipoprotein C3">3</a></li> <li><a href="/wiki/Apolipoprotein_C4" class="mw-redirect" title="Apolipoprotein C4">4</a></li></ul></li> <li><a href="/wiki/Apolipoprotein_D" title="Apolipoprotein D">APOD</a></li> <li><a class="mw-selflink selflink">APOE</a></li> <li><a href="/wiki/Apolipoprotein_H" title="Apolipoprotein H">APOH</a></li> <li><a href="/wiki/Serum_amyloid_A" title="Serum amyloid A">SAA</a> <ul><li><a href="/wiki/Serum_amyloid_A1" title="Serum amyloid A1">SAA1</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Extracellular <a href="/wiki/Enzyme" title="Enzyme">enzymes</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Lecithin%E2%80%94cholesterol_acyltransferase" class="mw-redirect" title="Lecithin—cholesterol acyltransferase">LCAT</a></li> <li><a href="/wiki/Hepatic_lipase" title="Hepatic lipase">LIPC</a></li> <li><a href="/wiki/Lipoprotein_lipase" title="Lipoprotein lipase">LPL</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Plant_lipid_transfer_proteins" title="Plant lipid transfer proteins">Lipid transfer proteins</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cholesterylester_transfer_protein" class="mw-redirect" title="Cholesterylester transfer protein">CETP</a></li> <li><a href="/wiki/Microsomal_triglyceride_transfer_protein" title="Microsomal triglyceride transfer protein">MTTP</a></li> <li><a href="/wiki/Phospholipid_transfer_protein" title="Phospholipid transfer protein">PLTP</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">Cell surface receptors</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>HDL: <a href="/wiki/SCARB1" title="SCARB1">SCARB1</a></li></ul> <ul><li>IDL: <a href="/wiki/Lipoprotein_receptor-related_protein" title="Lipoprotein receptor-related protein">LRP</a> <ul><li><a href="/wiki/LRP1" title="LRP1">LRP1</a></li> <li><a href="/wiki/LRP1B" title="LRP1B">LRP1B</a></li> <li><a href="/wiki/LRP2" title="LRP2">LRP2</a></li> <li><a href="/wiki/LRP3" title="LRP3">LRP3</a></li> <li><a href="/wiki/Low-density_lipoprotein_receptor-related_protein_4" title="Low-density lipoprotein receptor-related protein 4">LRP4</a></li> <li><a href="/wiki/LRP5" title="LRP5">LRP5</a></li> <li><a href="/w/index.php?title=LRP5L&action=edit&redlink=1" class="new" title="LRP5L (page does not exist)">LRP5L</a></li> <li><a href="/wiki/LRP6" title="LRP6">LRP6</a></li> <li><a href="/wiki/Low-density_lipoprotein_receptor-related_protein_8" title="Low-density lipoprotein receptor-related protein 8">LRP8</a></li> <li><a href="/wiki/LRP10" title="LRP10">LRP10</a></li> <li><a href="/wiki/LRP11" title="LRP11">LRP11</a></li> <li><a href="/w/index.php?title=LRP12&action=edit&redlink=1" class="new" title="LRP12 (page does not exist)">LRP12</a></li></ul></li> <li>LDL: <a href="/wiki/LDL_receptor" title="LDL receptor">LDLR</a></li> <li><a href="/wiki/LDL-receptor-related_protein-associated_protein" title="LDL-receptor-related protein-associated protein">LRPAP1</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/ATP-binding_cassette_transporter" class="mw-redirect" title="ATP-binding cassette transporter">ATP-binding <br />cassette transporter</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/ABCA1" title="ABCA1">ABCA1</a></li> <li><a href="/wiki/ABCG5" title="ABCG5">ABCG5</a></li> <li><a href="/wiki/ABCG8" title="ABCG8">ABCG8</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Longevity116" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Longevity" title="Template:Longevity"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Longevity" title="Template talk:Longevity"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Longevity" title="Special:EditPage/Template:Longevity"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Longevity116" style="font-size:114%;margin:0 4em"><a href="/wiki/Longevity" title="Longevity">Longevity</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ageing" title="Ageing">Ageing</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Old_age" title="Old age">Old age</a></li> <li><a href="/wiki/Longevity_myths" title="Longevity myths">Longevity myths</a></li> <li><a href="/wiki/Senescence" title="Senescence">Senescence</a> <ul><li><a href="/wiki/Aging-associated_diseases" title="Aging-associated diseases">aging-associated diseases</a></li> <li><a href="/wiki/Degenerative_disease" title="Degenerative disease">degenerative diseases</a></li> <li><a href="/wiki/Negligible_senescence" title="Negligible senescence">negligible senescence</a></li></ul></li> <li><a href="/wiki/Gerontology" title="Gerontology">Gerontology</a> <ul><li><a href="/wiki/Biogerontology" title="Biogerontology">biogerontology</a></li> <li><a href="/wiki/Cognitive_epidemiology" title="Cognitive epidemiology">cognitive epidemiology</a></li></ul></li> <li><a href="/wiki/Centenarian" title="Centenarian">Centenarian</a> <ul><li><a href="/wiki/Supercentenarian" title="Supercentenarian">supercentenarian</a></li> <li><a href="/wiki/Research_into_centenarians" title="Research into centenarians">research into centenarians</a></li></ul></li> <li><a href="/wiki/Life_expectancy" title="Life expectancy">Life expectancy</a> <ul><li><a href="/wiki/LGBT_life_expectancy" title="LGBT life expectancy">LGBT life expectancy</a></li></ul></li> <li><a href="/wiki/Maximum_life_span" title="Maximum life span">Maximum life span</a></li> <li><a href="/wiki/Biomarkers_of_aging" title="Biomarkers of aging">Biomarkers of aging</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Life_extension" title="Life extension">Life extension</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Outline_of_life_extension" title="Outline of life extension">Topic outline</a> <ul><li><a href="/wiki/Index_of_topics_related_to_life_extension" title="Index of topics related to life extension">index</a></li></ul></li> <li><a href="/wiki/Anti-aging_movement" title="Anti-aging movement">Anti-aging movement</a></li> <li><a href="/wiki/Biodemography_of_human_longevity" title="Biodemography of human longevity">Biodemography of human longevity</a></li> <li><a href="/wiki/Life_extension" title="Life extension">Indefinite lifespan</a></li> <li><a href="/wiki/Longevity_escape_velocity" title="Longevity escape velocity">Longevity escape velocity</a></li> <li>Methods <ul><li><a href="/wiki/Calorie_restriction" title="Calorie restriction">calorie restriction</a></li> <li><a href="/wiki/Diet_and_longevity" class="mw-redirect" title="Diet and longevity">Diet and longevity</a></li> <li><a href="/wiki/Gene_therapy" title="Gene therapy">gene therapy</a></li> <li><a href="/wiki/Nanomedicine" title="Nanomedicine">nanomedicine</a></li> <li><a href="/wiki/Organ_printing" title="Organ printing">organ printing</a></li> <li><a href="/wiki/Rejuvenation" title="Rejuvenation">rejuvenation</a></li> <li><a href="/wiki/Stem-cell_therapy" title="Stem-cell therapy">stem-cell therapy</a></li> <li><a href="/wiki/Strategies_for_engineered_negligible_senescence" title="Strategies for engineered negligible senescence">SENS</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Lists of<br /><a href="/wiki/Life_expectancy" title="Life expectancy">life expectancy</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">by country</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/List_of_countries_by_life_expectancy" title="List of countries by life expectancy">World</a></li> <li><a href="/wiki/List_of_African_countries_by_life_expectancy" title="List of African countries by life expectancy">Africa</a></li> <li><a href="/wiki/List_of_countries_in_the_Americas_by_life_expectancy" title="List of countries in the Americas by life expectancy">Americas</a> <ul><li><a href="/wiki/List_of_North_American_countries_by_life_expectancy" title="List of North American countries by life expectancy">North America</a></li> <li><a href="/wiki/List_of_South_American_countries_by_life_expectancy" title="List of South American countries by life expectancy">South America</a></li></ul></li> <li><a href="/wiki/List_of_Asian_countries_by_life_expectancy" title="List of Asian countries by life expectancy">Asia</a></li> <li><a href="/wiki/List_of_European_countries_by_life_expectancy" title="List of European countries by life expectancy">Europe</a></li> <li><a href="/wiki/List_of_Oceanian_countries_by_life_expectancy" title="List of Oceanian countries by life expectancy">Oceania</a></li> <li><a href="/wiki/List_of_world_regions_by_life_expectancy" title="List of world regions by life expectancy">World macroregions</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">regions of countries</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/List_of_Argentine_provinces_and_territories_by_life_expectancy" title="List of Argentine provinces and territories by life expectancy">Argentina</a></li> <li><a href="/wiki/List_of_Australian_states_by_life_expectancy" title="List of Australian states by life expectancy">Australia</a></li> <li><a href="/wiki/List_of_Belgian_provinces_by_life_expectancy" title="List of Belgian provinces by life expectancy">Belgium</a></li> <li><a href="/wiki/List_of_Brazilian_states_by_life_expectancy" title="List of Brazilian states by life expectancy">Brazil</a></li> <li><a href="/wiki/List_of_Canadian_provinces_and_territories_by_life_expectancy" title="List of Canadian provinces and territories by life expectancy">Canada</a></li> <li><a href="/wiki/List_of_Chinese_administrative_divisions_by_life_expectancy" title="List of Chinese administrative divisions by life expectancy">China</a> <ul><li><a href="/wiki/List_of_cities_in_China_by_life_expectancy" title="List of cities in China by life expectancy">Cities</a></li></ul></li> <li><a href="/wiki/List_of_French_departments_by_life_expectancy" title="List of French departments by life expectancy">France</a></li> <li><a href="/wiki/List_of_Finnish_regions_by_life_expectancy" title="List of Finnish regions by life expectancy">Finland</a></li> <li><a href="/wiki/List_of_German_states_by_life_expectancy" title="List of German states by life expectancy">Germany</a></li> <li><a href="/wiki/List_of_Greek_regions_by_life_expectancy" title="List of Greek regions by life expectancy">Greece</a></li> <li><a href="/wiki/List_of_Indian_states_by_life_expectancy_at_birth" title="List of Indian states by life expectancy at birth">India</a></li> <li><a href="/wiki/List_of_regions_of_Israel_and_Palestine_by_life_expectancy" title="List of regions of Israel and Palestine by life expectancy">Israel</a></li> <li><a href="/wiki/List_of_Italian_provinces_by_life_expectancy" title="List of Italian provinces by life expectancy">Italy</a></li> <li><a href="/wiki/List_of_Japanese_prefectures_by_life_expectancy" title="List of Japanese prefectures by life expectancy">Japan</a></li> <li><a href="/wiki/List_of_regions_of_Kazakhstan_by_life_expectancy" title="List of regions of Kazakhstan by life expectancy">Kazakhstan</a></li> <li><a href="/wiki/List_of_Mexican_states_by_life_expectancy" title="List of Mexican states by life expectancy">Mexico</a></li> <li><a href="/wiki/List_of_regions_of_Israel_and_Palestine_by_life_expectancy" title="List of regions of Israel and Palestine by life expectancy">Palestine</a></li> <li><a href="/wiki/List_of_federal_subjects_of_Russia_by_life_expectancy" title="List of federal subjects of Russia by life expectancy">Russia</a></li> <li><a href="/wiki/List_of_South_African_provinces_by_life_expectancy" title="List of South African provinces by life expectancy">South Africa</a></li> <li><a href="/wiki/List_of_Spanish_provinces_by_life_expectancy" title="List of Spanish provinces by life expectancy">Spain</a></li> <li><a href="/wiki/List_of_Swedish_counties_by_life_expectancy" title="List of Swedish counties by life expectancy">Sweden</a></li> <li><a href="/wiki/List_of_Tajikistani_regions_by_life_expectancy" title="List of Tajikistani regions by life expectancy">Tajikistan</a></li> <li><a href="/wiki/List_of_Turkish_provinces_by_life_expectancy" title="List of Turkish provinces by life expectancy">Turkey</a></li> <li><a href="/wiki/List_of_British_regions_by_life_expectancy" title="List of British regions by life expectancy">UK</a></li> <li><a href="/wiki/List_of_U.S._states_and_territories_by_life_expectancy" title="List of U.S. states and territories by life expectancy">USA</a> <ul><li><a href="/wiki/List_of_U.S._counties_with_shortest_life_expectancy" class="mw-redirect" title="List of U.S. counties with shortest life expectancy">shortest</a></li> <li><a href="/wiki/List_of_U.S._counties_with_longest_life_expectancy" class="mw-redirect" title="List of U.S. counties with longest life expectancy">longest</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">regions by continents</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/List_of_African_regions_by_life_expectancy" title="List of African regions by life expectancy">Africa</a></li> <li><a href="/wiki/List_of_Asian_regions_by_life_expectancy" title="List of Asian regions by life expectancy">Asia</a></li> <li><a href="/wiki/List_of_European_regions_by_life_expectancy" title="List of European regions by life expectancy">Europe</a></li> <li><a href="/wiki/List_of_Oceanian_regions_by_life_expectancy" title="List of Oceanian regions by life expectancy">Oceania</a></li> <li><a href="/wiki/List_of_South_American_regions_by_life_expectancy" title="List of South American regions by life expectancy">South America</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Records</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Longevity_claims" title="Longevity claims">Longevity claims</a></li> <li><a href="/wiki/Oldest_people" title="Oldest people">Oldest people</a> <ul><li><a href="/wiki/List_of_the_verified_oldest_people" title="List of the verified oldest people">verified</a></li> <li><a href="/wiki/List_of_the_oldest_people_by_country" title="List of the oldest people by country">by country</a></li> <li><a href="/wiki/List_of_oldest_living_people" title="List of oldest living people">living</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Immortality" title="Immortality">Immortality</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Biological_immortality" title="Biological immortality">Biological immortality</a> <ul><li><a href="/wiki/Regeneration_(biology)" title="Regeneration (biology)">Regeneration</a></li></ul></li> <li><a href="/wiki/Digital_immortality" title="Digital immortality">Digital immortality</a></li> <li><a href="/wiki/Eternal_youth" title="Eternal youth">Eternal youth</a></li> <li><a href="/wiki/Immortality_in_fiction" title="Immortality in fiction">Immortality in fiction</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Longevity genes</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/FOXO3" title="FOXO3">FOXO3</a></li> <li><a class="mw-selflink selflink">APOE</a></li> <li><a href="/wiki/Cholesteryl_ester_transfer_protein" title="Cholesteryl ester transfer protein">CETP</a></li> <li><a href="/wiki/Angiotensin-converting_enzyme" title="Angiotensin-converting enzyme">ACE</a></li> <li><a href="/wiki/Interleukin_6" title="Interleukin 6">IL6</a></li> <li><a href="/wiki/Klotho_(biology)" title="Klotho (biology)">Klotho</a></li> <li><a href="/wiki/Sirtuin_1" title="Sirtuin 1">SIRT1</a></li> <li><a href="/wiki/Tumor_necrosis_factor" title="Tumor necrosis factor">TNF</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Related</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Blue_zone" title="Blue zone">Blue zone</a></li> <li><a href="/wiki/Longevity_insurance" title="Longevity insurance">Longevity insurance</a></li> <li><a href="/wiki/Longevity_risk" title="Longevity risk">Longevity risk</a></li> <li><a href="/wiki/Transhumanist_politics" title="Transhumanist politics">Transhumanist politics</a></li> <li><a href="/wiki/List_of_longest-living_organisms" title="List of longest-living organisms">Longest-living organisms</a></li></ul> </div></td></tr></tbody></table></div>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?useformat=desktop&type=1x1&usesul3=0" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div 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