APOE Gene

HGNC Family	Apolipoproteins (APO)
Name	apolipoprotein E
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Apolipoprotein E (APOE) plays a central role in the central nervous system as a major cholesterol carrier that supports lipid transport, neuronal repair, and synaptic plasticity. In addition to facilitating lipid redistribution and injury repair, APOE binds hydrophobic amyloid‐β (Aβ) peptides and modulates their aggregation and clearance. Notably, the three common isoforms of APOE (ε2, ε3, and ε4) exhibit distinct functional profiles; ε4 is associated with impaired Aβ clearance, increased amyloid deposition, and a heightened proinflammatory milieu, while the ε2 allele appears protective (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, APOE influences tau pathology and neurodegeneration independently of Aβ. Experimental models have demonstrated that APOE4 promotes elevated tau accumulation, exacerbates neuroinflammatory responses, and accelerates brain atrophy, whereas the absence of APOE is largely protective (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " APOE4 also compromises cerebrovascular integrity by triggering a proinflammatory cascade—involving molecules such as cyclophilin A, NF‑κB, and matrix‐metalloproteinase‑9—that disrupts blood–brain barrier function (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, functional imaging studies reveal that even in young adulthood, APOE4 carriers exhibit altered brain metabolism and connectivity patterns that foreshadow later neurodegenerative changes (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of APOE in regulating lipid homeostasis, amyloid and tau dynamics, neuroinflammation, and vascular function—all of which contribute to Alzheimer’s disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chia-Chen Liu, Chia-Chan Liu, Takahisa Kanekiyo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Neurol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrneurol.2012.263"}], "href": "https://doi.org/10.1038/nrneurol.2012.263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23296339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23296339"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jungsu Kim, Jacob M Basak, David M Holtzman "}, {"type": "b", "children": [{"type": "t", "text": "The role of apolipoprotein E in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2009.06.026"}], "href": "https://doi.org/10.1016/j.neuron.2009.06.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19679070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19679070"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yang Shi, Kaoru Yamada, Shane Antony Liddelow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature24016"}], "href": "https://doi.org/10.1038/nature24016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28959956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28959956"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Robert D Bell, Ethan A Winkler, Itender Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apolipoprotein E controls cerebrovascular integrity via cyclophilin A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11087"}], "href": "https://doi.org/10.1038/nature11087"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22622580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22622580"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nicola Filippini, Bradley J MacIntosh, Morgan G Hough, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0811879106"}], "href": "https://doi.org/10.1073/pnas.0811879106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19357304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19357304"}]}]}]}
Synonyms	AD2, LDLCQ5, LPG, APO-E, ApoE4
Proteins	APOE_HUMAN
NCBI Gene ID	348
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

APOE has 37,153 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 142 datasets.

Click the + buttons to view associations for APOE from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

APOE Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of APOE gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of APOE gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of APOE gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of APOE gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of APOE gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of APOE gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of APOE gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of APOE gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of APOE gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of APOE gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of APOE gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of APOE gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with APOE protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with APOE gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of APOE gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of APOE gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of APOE gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with APOE gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with APOE gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of APOE gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing APOE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing APOE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with APOE protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with APOE protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing APOE protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of APOE gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with APOE gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with APOE gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with APOE gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with APOE gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of APOE protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by APOE gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving APOE gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving APOE gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with APOE gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with APOE gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with APOE gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with APOE gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with APOE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with APOE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.