Gene Information
Gene Symbol
Entrez Gene ID
Gene Name
Apolipoprotein E
Chromosomal Location
The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
RefSeq DNA
RefSeq mRNA

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0000302 Biological process Response to reactive oxygen species NAS 11743999
GO:0001937 Biological process Negative regulation of endothelial cell proliferation IDA 9685360
GO:0006641 Biological process Triglyceride metabolic process IDA 9649566
GO:0006641 Biological process Triglyceride metabolic process IMP 3771793
GO:0006695 Biological process Cholesterol biosynthetic process IBA 21873635
Protein Information
Protein Name
Apolipoprotein E, apolipoprotein E3
APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating to the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:9395455, PubMed:14754908, PubMed:23620513). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:8939961, PubMed:25173806). APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). APOE, may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074).
Refseq Proteins
Pfam Accession Pfam ID
PF01442 Apolipoprotein

Cholesterol metabolism
Alzheimer disease


Nuclear signaling by ERBB4
Scavenging by Class A Receptors
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
Post-translational protein phosphorylation
Chylomicron assembly
Chylomicron remodeling
Chylomicron clearance
HDL remodeling
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
Retinoid metabolism and transport

ENSP00000257430 P25054 P25054
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Associated Diseases

Disease groupDisease NameReferences
Cardiovascular Diseases
Hypertensive disease
Acute Coronary Syndrome
Ischemic Cardiomyopathy
Myocardial Infarction
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
Inflammation and atherosclerosis,hyperandrogenism, insulin resistance,hypertriglyceridaemia,type 2 diabetes mellitus and future cardiovascular diseases 
Rotterdam criteria 
Decreased total and apoE-containing HDL-PAF-AH activities and increased serum MDA concentration may contribute to the pathogenesis of PCOS and potentially link to related complications responsible for oxidative stress and inflammation such as an increased risk for type 2 diabetes mellitus and/or future cardiovascular diseases in PCOS patients. 
Apo-A1, apoB,SHBG 
Insulin resistance,atherosclerosis 
Elevated OxLDL and the relation of apoE and nonesterified fatty acids with insulin resistance suggest that women with PCOS are at increased risk for premature atherosclerosis. 
Apo E2 allele 
Cardiovascular risk 
Apo E3 allele 
Rotterdam criteria 
Turkey-129 PCOS and 91 controls 
The Apo E3 allele was found at a significantly higher frequency in the PCOS patient group compared with the control group. 

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