APOE apolipoprotein E [Homo sapiens] - Gene

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Summary

Official Symbol: APOEprovided by HGNC
Official Full Name: apolipoprotein Eprovided by HGNC
Primary source: HGNC:613
See related: Ensembl:ENSG00000130203; HPRD:00135; MIM:107741; Vega:OTTHUMG00000128901
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AD2; LPG; LDLCQ5; MGC1571
Summary: Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and APOC2. Defects in apolipoprotein E 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, Jul 2008]

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Genomic context

Location :: 19q13.2

Sequence :: Chromosome: 19; NC_000019.9 (45409039..45412650)

See APOE in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

LRP1 enables apoE to accumulate in an early endosomal recycling compartment that serves as a pool for the intracellular formation and subsequent re-secretion of apoE-enriched HDL particles.
Title: Low density lipoprotein receptor-related protein 1 dependent endosomal trapping and recycling of apolipoprotein E.
The ApoE4 allele may be associated with an increased risk for development of atherosclerosis by elevated levels of total cholesterol in children with family history of coronary artery disease.
Title: The association of apolipoprotein E polymorphism and lipid levels in children with a family history of premature coronary artery disease.
Abeta42 is a stronger predictor of progression to Alzheimer's disease in APOE epsilon4 non-carriers than in carriers.
Title: Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype.
These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.
Title: Association between ApoE phenotypes and telomere erosion in Alzheimer's disease.
The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type.
Title: Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE.
Men are normally protected by androgens against bulbar amyotrophic lateral sclerosis; the APOepsilon4 allele inhibits this protection, perhaps by interfering with the androgen pathway.
Title: APOE ε4 allele is associated with an increased risk of bulbar-onset amyotrophic lateral sclerosis in men.
APOE e4 genotype prevalence varies among alzheimer's disease patients by region and within each country
Title: Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis.
In this older non-demented population APOE-epsilon4 carriers may be more vulnerable to the potential detrimental effect of hypothalamic-pituitary-adrenal axis dysfunction on verbal memory performance.
Title: Salivary cortisol, APOE-ε4 allele and cognitive decline in a prospective study of older persons.
Serum ApoE level was independently associated with urinary albumin excretion in type 2 diabetic patients from Shanghai, China.
Title: Circulating ApoE level is independently associated with urinary albumin excretion in type 2 diabetic patients.
The results suggest that olfactory processing speed may be a useful measure for detecting and following the effects of adiposity on brain integrity and cognitive function in those at genetic risk for AD.
Title: Adiposity measures predict olfactory processing speed in older adult carriers of the apolipoprotein E ε4 allele.

Submit: New GeneRIF Correction See all (1182)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.

A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease.

Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease.

Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.

Common variants at 30 loci contribute to polygenic dyslipidemia.

Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.

Examination of the current top candidate genes for AD in a genome-wide association study.

Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease.

Genetic Signatures of Exceptional Longevity in Humans.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

Genome-wide analysis of genetic loci associated with Alzheimer disease.

Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.

Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort.

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.

Longitudinal genome-wide association of cardiovascular disease risk factors in the Bogalusa heart study.

Macular degeneration, age-related

MIM: 603075

Myocardial infarction susceptibility

MIM: 107741

Newly identified loci that influence lipid concentrations and risk of coronary artery disease.

Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein.

Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

Sorl1 as an Alzheimer's disease predisposition gene?

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease.

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 causes increased neurotoxicity in human neuronal cultures with the ApoE4 allele	PubMed
Tat	tat	Binding of HIV-1 Tat to LRP inhibits neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor and amyloid beta-protein	PubMed
	tat	The antioxidant properties of human lipidated apoE3 protects neurons from Tat-induced toxicity	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000032.1	NP_000605.1	CNTF	BIND	PubMed	Apolipoprotein E binds to ciliary neurotrophic factor
NP_000032.1	NP_000605.1	CNTF	BIND	PubMed	Apolipoprotein E binds to ciliary neurotrophic factor
NP_000032.1	NP_671491.1	HCVgp1	BIND	PubMed	ApoE interacts with NS5A. This interaction was modeled on a demonstrated interaction between ApoE from an unspecified species and NS5A from Hepatitis C virus type 1a isolate H77.
NP_000032.1	CAB46677.1		BIND	PubMed	ApoE interacts with NS5A. This interaction was modeled on a demonstrated interaction between ApoE from an unspecified species and NS5A from Hepatitis C virus type 1b isolate Con1.
P02649	P01023	A2M	HPRD	PubMed
P02649	P02768	ALB	HPRD	PubMed
P02649	P02649	APOE	HPRD	PubMed
P02649	P05067	APP	HPRD	PubMed
P02649	P26441	CNTF	HPRD	PubMed
P02649	P07858	CTSB	HPRD	PubMed
P02649	P01130	LDLR	HPRD	PubMed
P02649	Q07954	LRP1	HPRD	PubMed
P02649	P98164	LRP2	HPRD	PubMed
P02649	Q14114	LRP8	HPRD	PubMed
P02649	P11137	MAP2	HPRD	PubMed
P02649	P10636	MAPT	HPRD	PubMed
P02649	P07197	NEFM	HPRD	PubMed
P02649	P55058	PLTP	HPRD	PubMed
P02649	P04156	PRNP	HPRD	PubMed
P02649	Q8WTV0	SCARB1	HPRD	PubMed
P02649	P98155	VLDLR	HPRD	PubMed
BioGRID:106845	BioGRID:106524	A2M	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:106845	BioGRID:110215	LRP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106845	BioGRID:110216	LRP2	BioGRID	PubMed	Reconstituted Complex
BioGRID:106845	BioGRID:113579	LRP8	BioGRID	PubMed	Reconstituted Complex
BioGRID:106845	BioGRID:110308	MAPT	BioGRID	PubMed	Protein-peptide; Reconstituted Complex
BioGRID:106845	BioGRID:110818	NEFM	BioGRID	PubMed	Reconstituted Complex
BioGRID:106845	BioGRID:111374	PLTP	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106845	BioGRID:207808	Set	BioGRID	PubMed	Reconstituted Complex
BioGRID:106845	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
antioxidant activity	IDA Inferred from Direct Assay more info	PubMed
beta-amyloid binding	IDA Inferred from Direct Assay more info	PubMed
cholesterol transporter activity	IEA Inferred from Electronic Annotation more info
heparin binding	IDA Inferred from Direct Assay more info	PubMed
identical protein binding	IDA Inferred from Direct Assay more info	PubMed
lipid binding	IDA Inferred from Direct Assay more info	PubMed
lipid transporter activity	IDA Inferred from Direct Assay more info	PubMed
lipoprotein particle binding	IEA Inferred from Electronic Annotation more info
low-density lipoprotein particle receptor binding	IDA Inferred from Direct Assay more info	PubMed
low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
metal chelating activity	IDA Inferred from Direct Assay more info	PubMed
phosphatidylcholine-sterol O-acyltransferase activator activity	IDA Inferred from Direct Assay more info	PubMed
phospholipid binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
tau protein binding	IPI Inferred from Physical Interaction more info	PubMed
very-low-density lipoprotein particle receptor binding	IDA Inferred from Direct Assay more info	PubMed
very-low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Cdc42 protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
G-protein coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
aging	IEA Inferred from Electronic Annotation more info
anti-apoptosis	IDA Inferred from Direct Assay more info	PubMed
artery morphogenesis	IEA Inferred from Electronic Annotation more info
cGMP-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
cardiovascular system development	IEA Inferred from Electronic Annotation more info
cell death	IEA Inferred from Electronic Annotation more info
cellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
cellular response to growth factor stimulus	IEA Inferred from Electronic Annotation more info
cholesterol catabolic process	IEA Inferred from Electronic Annotation more info
cholesterol efflux	IDA Inferred from Direct Assay more info	PubMed
cholesterol homeostasis	IDA Inferred from Direct Assay more info	PubMed
cholesterol metabolic process	IDA Inferred from Direct Assay more info	PubMed
cholesterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
chylomicron remnant clearance	IMP Inferred from Mutant Phenotype more info	PubMed
cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
high-density lipoprotein particle assembly	IDA Inferred from Direct Assay more info	PubMed
high-density lipoprotein particle clearance	IDA Inferred from Direct Assay more info	PubMed
high-density lipoprotein particle remodeling	IGI Inferred from Genetic Interaction more info	PubMed
induction of apoptosis	IDA Inferred from Direct Assay more info	PubMed
intracellular transport	TAS Traceable Author Statement more info	PubMed
lipid homeostasis	IEA Inferred from Electronic Annotation more info
lipid metabolic process	TAS Traceable Author Statement more info
lipoprotein biosynthetic process	IEA Inferred from Electronic Annotation more info
lipoprotein catabolic process	IEA Inferred from Electronic Annotation more info
lipoprotein metabolic process	TAS Traceable Author Statement more info
low-density lipoprotein particle remodeling	IEA Inferred from Electronic Annotation more info
maintenance of location in cell	IEA Inferred from Electronic Annotation more info
negative regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of blood coagulation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of blood vessel endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of inflammatory response	IC Inferred by Curator more info	PubMed
negative regulation of platelet activation	IDA Inferred from Direct Assay more info	PubMed
nitric oxide mediated signal transduction	IDA Inferred from Direct Assay more info	PubMed
peripheral nervous system axon regeneration	IEA Inferred from Electronic Annotation more info
phospholipid efflux	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cGMP biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
positive regulation of cholesterol efflux	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cholesterol efflux	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of cholesterol esterification	IDA Inferred from Direct Assay more info	PubMed
positive regulation of low-density lipoprotein particle receptor catabolic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of nitric-oxide synthase activity	IDA Inferred from Direct Assay more info	PubMed
receptor-mediated endocytosis	IDA Inferred from Direct Assay more info	PubMed
regulation of axon extension	TAS Traceable Author Statement more info	PubMed
regulation of gene expression	IEA Inferred from Electronic Annotation more info
regulation of neuronal synaptic plasticity	TAS Traceable Author Statement more info	PubMed
response to dietary excess	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to reactive oxygen species	NAS Non-traceable Author Statement more info	PubMed
reverse cholesterol transport	IDA Inferred from Direct Assay more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
synaptic transmission, cholinergic	TAS Traceable Author Statement more info	PubMed
triglyceride metabolic process	IDA Inferred from Direct Assay more info	PubMed
triglyceride metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
vasodilation	IEA Inferred from Electronic Annotation more info
very-low-density lipoprotein particle clearance	IDA Inferred from Direct Assay more info	PubMed
very-low-density lipoprotein particle clearance	IMP Inferred from Mutant Phenotype more info	PubMed
very-low-density lipoprotein particle remodeling	IDA Inferred from Direct Assay more info	PubMed
very-low-density lipoprotein particle remodeling	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
chylomicron	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	NAS Non-traceable Author Statement more info	PubMed
cytoplasm	TAS Traceable Author Statement more info	PubMed
dendrite	NAS Non-traceable Author Statement more info	PubMed
early endosome	IEA Inferred from Electronic Annotation more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info
extrinsic to external side of plasma membrane	IEA Inferred from Electronic Annotation more info
high-density lipoprotein particle	IDA Inferred from Direct Assay more info	PubMed
intermediate-density lipoprotein particle	IDA Inferred from Direct Assay more info	PubMed
late endosome	IEA Inferred from Electronic Annotation more info
low-density lipoprotein particle	IDA Inferred from Direct Assay more info	PubMed
microtubule	IEA Inferred from Electronic Annotation more info
neuronal cell body	NAS Non-traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
very-low-density lipoprotein particle	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: apolipoprotein E

Names: apolipoprotein E; apo-E; apolipoprotein E3

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007084.2 RefSeqGene

Range

5001..8612

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000041.2 → NP_000032.1 apolipoprotein E precursor

Status: REVIEWED

Source sequence(s)

BC003557, BU848796

Consensus CDS

CCDS12647.1

UniProtKB/Swiss-Prot

P02649

Related

ENSP00000252486, OTTHUMP00000159143, ENST00000252486, OTTHUMT00000250865

Conserved Domains (1) summary

pfam01442
Location:80 – 299
Blast Score: 299

Apolipoprotein; Apolipoprotein A1/A4/E domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p5 Primary Assembly

Range

45409039..45412650

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

41839825..41843436

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB035149.1	BAA96080.1
genomic	AC011481.4 (48604..52215)	None
genomic	AF050154.1	AAD02505.1
genomic	AF261279.1	AAG27089.1
genomic	AY077451.1	AAL82810.1
genomic	CH471126.1	EAW57306.1
genomic	FJ525876.1	ACN81314.1
genomic	M10065.1	AAB59397.1
genomic	X92000.1	CAA63051.1
mRNA	AK314898.1	BAG37412.1
mRNA	BC003557.1	AAH03557.1
mRNA	BU848796.1	None
mRNA	K00396.1	AAB59546.1
mRNA	M12529.1	AAB59518.1
mRNA	X00199.1	CAA25017.1
mRNA	Z70760.1	CAA94806.1
other-genetic	DQ892548.2	ABM83474.1
other-genetic	DQ895759.2	ABM86685.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P02649.1	GenPept	UniProtKB/Swiss-Prot:P02649
Q13791	GenPept	UniProtKB/TrEMBL:Q13791
Q6LA97	GenPept	UniProtKB/TrEMBL:Q6LA97
Q6LBZ1	GenPept	UniProtKB/TrEMBL:Q6LBZ1
Q8TCZ8	GenPept	UniProtKB/TrEMBL:Q8TCZ8