APOE

Summary

APOE (apolipoprotein E, HGNC:613) is a protein-coding gene on chromosome 19q13.32, encoding Apolipoprotein E (P02649). 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.

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.

Source: NCBI Gene 348 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alzheimer disease 2 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 403
• Clinical variants (ClinVar): 274 total — 11 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 84
• MANE Select transcript: NM_000041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:613
Approved symbol	APOE
Name	apolipoprotein E
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130203
Ensembl biotype	protein_coding
OMIM	107741
Entrez	348

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 31 protein_coding, 1 retained_intron

ENST00000252486, ENST00000425718, ENST00000434152, ENST00000446996, ENST00000485628, ENST00000864817, ENST00000864820, ENST00000864822, ENST00000864824, ENST00000864826, ENST00000864828, ENST00000864829, ENST00000864830, ENST00000864831, ENST00000864832, ENST00000864833, ENST00000864834, ENST00000864835, ENST00000864836, ENST00000864837, ENST00000864838, ENST00000864839, ENST00000864840, ENST00000864841, ENST00000864842, ENST00000864843, ENST00000864844, ENST00000864845, ENST00000864846, ENST00000864847, ENST00000864848, ENST00000864849

RefSeq mRNA: 5 — MANE Select: NM_000041 NM_000041, NM_001302688, NM_001302689, NM_001302690, NM_001302691

CCDS: CCDS12647

Canonical transcript exons

ENST00000252486 — 4 exons

Exon	Start	End
ENSE00000893952	44907760	44907952
ENSE00000893954	44908533	44909393
ENSE00001048576	44905796	44905841
ENSE00003577086	44906602	44906667

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 715.8711 / max 16971.5124, expressed in 1372 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176325	708.4376	1361
176329	2.2061	398
176328	2.0913	374
176327	1.9501	420
176330	1.0117	291
176326	0.1742	93

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland	UBERON:0001234	99.93	gold quality
left adrenal gland cortex	UBERON:0035825	99.93	gold quality
right adrenal gland cortex	UBERON:0035827	99.93	gold quality
right adrenal gland	UBERON:0001233	99.92	gold quality
right lobe of liver	UBERON:0001114	99.90	gold quality
adrenal cortex	UBERON:0001235	99.90	gold quality
nucleus accumbens	UBERON:0001882	99.82	gold quality
adrenal gland	UBERON:0002369	99.80	gold quality
amygdala	UBERON:0001876	99.76	gold quality
liver	UBERON:0002107	99.65	gold quality
hypothalamus	UBERON:0001898	99.57	gold quality
caudate nucleus	UBERON:0001873	99.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.47	gold quality
putamen	UBERON:0001874	99.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.40	gold quality
spinal cord	UBERON:0002240	99.38	gold quality
right frontal lobe	UBERON:0002810	99.38	gold quality
dorsal root ganglion	UBERON:0000044	99.27	gold quality
lateral globus pallidus	UBERON:0002476	99.22	gold quality
cerebellar cortex	UBERON:0002129	99.17	gold quality
cerebellar hemisphere	UBERON:0002245	99.16	gold quality
anterior cingulate cortex	UBERON:0009835	99.11	gold quality
cingulate cortex	UBERON:0003027	99.07	gold quality
right ovary	UBERON:0002118	99.05	gold quality
adult mammalian kidney	UBERON:0000082	99.04	gold quality
adrenal tissue	UBERON:0018303	99.02	gold quality
skin of abdomen	UBERON:0001416	98.98	gold quality
cerebellum	UBERON:0002037	98.90	gold quality
right lung	UBERON:0002167	98.80	gold quality
lymph node	UBERON:0000029	98.76	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 45.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	13467.11
E-MTAB-6308	yes	13293.76
E-MTAB-8495	yes	12564.23
E-MTAB-6653	yes	12081.81
E-MTAB-10287	yes	11038.80
E-CURD-126	yes	9798.11
E-MTAB-10553	yes	9610.72
E-MTAB-11121	yes	9240.27
E-HCAD-15	yes	8845.23
E-HCAD-4	yes	7970.17
E-GEOD-124263	yes	7506.17
E-MTAB-8410	yes	6929.34
E-MTAB-7316	yes	6651.53
E-CURD-122	yes	6556.21
E-HCAD-9	yes	6046.29

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HMGXB4	Repression
LGMN	Repression

Upstream regulators (CollecTRI, top): AEBP1, AP1, ATF4, BHLHA15, BMP2, CEBPG, DNAJA4, FOXM1, IRF6, JUN, NFKB1, NFKB, NR1H2, NR1H3, NR1H4, NR2C2, PPARD, PPARG, RELA, SP1, SPI1, STAT1, TCF3, TFAP2A, TFAP2B, TP53, TREM2, ZIC1, ZIC2, ZNF202

miRNA regulators (miRDB)

2 targeting APOE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-7704	95.30	62.35	115

Literature-anchored findings (GeneRIF, showing 6)

• ApoE inhibits the depolymerization of beta 2-microglobulin-related amyloid fibrils at pH 7.5, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta 2-microglobulin in the fibrils. (PMID:11456487)
• Patients with multiple sclerosis and allelic polymorphism of APOE epsilon 4 have a significantly higher progression index of disability and a worse ranked multiple sclerosis severity score than their non-epsilon 4 counterparts. (PMID:11552016)
• APOE polymorphisms in cerebral amyloid angiopathy (PMID:11676289)
• gene polymorphism as a risk factor for cerebral amyloid angiopathy-related hemorrhage. (PMID:11676291)
• PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD. (PMID:11803456)
• Cellular and secreted levels of apoE are reduced (15 and 30%, respectively, over a 24-h period) by addition of exogenous lactosyl ceramide (LacSer) to cultured macrophages, indicating a proatherogenic role for LacCer. (PMID:11820771)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apoeb	ENSDARG00000040295
danio_rerio	apoea	ENSDARG00000102004
mus_musculus	Apoe	ENSMUSG00000002985
rattus_norvegicus	Apoe	ENSRNOG00000018454

Paralogs (3): APOA5 (ENSG00000110243), APOA4 (ENSG00000110244), APOA1 (ENSG00000118137)

Protein

Protein identifiers

Apolipoprotein E — P02649 (reviewed: P02649)

All UniProt accessions (5): P02649, A0A0S2Z3D5, E7ERP7, E9PEV4, H0Y7L5

UniProt curated annotations — full annotation on UniProt →

Function. 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. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. 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). 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. Finally, APOE also has 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. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. 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. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis. 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. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. APOE is also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells. Binds to the immune cell receptor LILRB4. 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. (Microbial infection) Through its interaction with HCV envelope glycoprotein E2, participates in the attachment of HCV to HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface and to the assembly, maturation and infectivity of HCV viral particles. This interaction is probably promoted via the up-regulation of cellular autophagy by the virus.

Subunit / interactions. Homotetramer. May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear. May interact with MAPT. May interact with MAP2. In the cerebrospinal fluid, interacts with secreted SORL1. Interacts with PMEL; this allows the loading of PMEL luminal fragment on ILVs to induce fibril nucleation. (Microbial infection) Interacts with hepatitis C virus (HCV) envelope glycoprotein E2; this interaction is required for HCV infectivity and production.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Extracellular vesicle. Endosome. Multivesicular body.

Tissue specificity. Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph. Mainly synthesized by liver hepatocytes. Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus. It is also expressed by cells of the peripheral nervous system. Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues.

Post-translational modifications. APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific. Plasma APOE undergoes desialylation and is less glycosylated and sialylated than the cellular form. Glycosylation is not required for proper expression and secretion. O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308. Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold). Phosphorylated by FAM20C in the extracellular medium. Undergoes C-terminal proteolytic processing in neurons. C-terminally truncated APOE has a tendency to form neurotoxic intracellular neurofibrillary tangle-like inclusions in neurons.

Disease relevance. Hyperlipoproteinemia 3 (HLPP3) [MIM:617347] A disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The disease is caused by variants affecting the gene represented in this entry. The vast majority of the patients are homozygous for APOE2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE4 variant are at higher risk of CAD. Alzheimer disease 2 (AD2) [MIM:104310] A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. Disease susceptibility is associated with variants affecting the gene represented in this entry. The APOE4 allele (APOE form E4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE4 alleles in 42 families with late onset AD. Thus APOE4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known. Sea-blue histiocyte disease (SBHD) [MIM:269600] Characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses. The disease is caused by variants affecting the gene represented in this entry. Lipoprotein glomerulopathy (LPG) [MIM:611771] Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. There are three common APOE alleles identified: APOE2/APOE-epsilon2/E2, APOE3/APOE-epsilon3/E3, and APOE4/APOE-epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms differentially present Cys and Arg residues at positions 130 and 176. The most common allele in the human population is APOE3 which sequence is the one displayed in that entry with a Cys at position 130 and an Arg at position 176. Common APOE variants influence lipoprotein metabolism in healthy individuals. Additional variants have been described and are described relative to the three common alleles. Allele APOE*4 is strongly associated with risk for severe COVID-19, increases susceptibility to SARS-CoV-2 infection in neurons and astrocytes.

Miscellaneous. Binds to and activates LILRB4 on acute myeloid leukemia (AML) cells which leads to suppression of T cell proliferation and promotion of AML cell migration and infiltration.

Similarity. Belongs to the apolipoprotein A1/A4/E family.

RefSeq proteins (5): NP_000032, NP_001289617, NP_001289618, NP_001289619, NP_001289620 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000074	ApoA_E	Family
IPR050163	Apolipoprotein_A1/A4/E	Family

Pfam: PF01442

UniProt features (89 total): sequence variant 34, helix 12, mutagenesis site 10, repeat 8, glycosylation site 7, region of interest 5, strand 4, turn 3, binding site 2, modified residue 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7FCR	X-RAY DIFFRACTION	1.4
8AX9	X-RAY DIFFRACTION	1.55
8AX8	X-RAY DIFFRACTION	1.55
7FCS	X-RAY DIFFRACTION	1.6
1GS9	X-RAY DIFFRACTION	1.7
6NCO	X-RAY DIFFRACTION	1.71
1OR3	X-RAY DIFFRACTION	1.73
8CE0	X-RAY DIFFRACTION	1.75
1NFN	X-RAY DIFFRACTION	1.8
6NCN	X-RAY DIFFRACTION	1.82
1BZ4	X-RAY DIFFRACTION	1.85
1H7I	X-RAY DIFFRACTION	1.9
8CDY	X-RAY DIFFRACTION	1.9
1EA8	X-RAY DIFFRACTION	1.95
7UVJ	X-RAY DIFFRACTION	1.99
1B68	X-RAY DIFFRACTION	2
1NFO	X-RAY DIFFRACTION	2
6V7M	X-RAY DIFFRACTION	2
1LPE	X-RAY DIFFRACTION	2.25
1LE4	X-RAY DIFFRACTION	2.5
1OR2	X-RAY DIFFRACTION	2.5
6IWB	X-RAY DIFFRACTION	2.5
1LE2	X-RAY DIFFRACTION	3
8GRX	ELECTRON MICROSCOPY	3
1OEF	SOLUTION NMR
1OEG	SOLUTION NMR
2KC3	SOLUTION NMR
2KNY	SOLUTION NMR
2L7B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02649-F1	76.13	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 162–165; 229–236

Post-translational modifications (2): 143, 147

Glycosylation sites (7): 26, 36, 93, 212, 307, 308, 314

Mutagenesis-validated functional residues (10):

Position	Phenotype
79	changes the plasma lipoprotein distribution of apoe4 to the hdl.
127	no effect on plasma lipoprotein distribution.
157	increased binding to ldl receptor; when associated with a-167.
158	decreased binding to ldl receptor.
161	decreased binding to ldl receptor.
162	decreased binding to ldl receptor.
167	increased binding to ldl receptor; when associated with r-157.
168	decreased binding to ldl receptor.
172	restores the ldl receptor binding activity of apoe2.
212	loss of o-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-8963888	Chylomicron assembly
R-HSA-8963901	Chylomicron remodeling
R-HSA-8964026	Chylomicron clearance
R-HSA-8964058	HDL remodeling
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-975634	Retinoid metabolism and transport
R-HSA-977225	Amyloid fiber formation
R-HSA-1236394	Signaling by ERBB4
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-2187338	Visual phototransduction
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-8964043	Plasma lipoprotein clearance

MSigDB gene sets: 1007 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_COGNITION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS

GO Biological Process (111): response to reactive oxygen species (GO:0000302), negative regulation of endothelial cell proliferation (GO:0001937), response to dietary excess (GO:0002021), triglyceride metabolic process (GO:0006641), cholesterol catabolic process (GO:0006707), intracellular calcium ion homeostasis (GO:0006874), receptor-mediated endocytosis (GO:0006898), cytoskeleton organization (GO:0007010), G protein-coupled receptor signaling pathway (GO:0007186), synaptic transmission, cholinergic (GO:0007271), long-term memory (GO:0007616), cholesterol metabolic process (GO:0008203), gene expression (GO:0010467), negative regulation of platelet activation (GO:0010544), negative regulation of endothelial cell migration (GO:0010596), negative regulation of gene expression (GO:0010629), negative regulation of platelet-derived growth factor receptor signaling pathway (GO:0010642), positive regulation of cholesterol efflux (GO:0010875), lipid transport involved in lipid storage (GO:0010877), positive regulation of neuron projection development (GO:0010976), negative regulation of neuron projection development (GO:0010977), long-chain fatty acid transport (GO:0015909), protein import (GO:0017038), virion assembly (GO:0019068), negative regulation of blood coagulation (GO:0030195), regulation of axon extension (GO:0030516), neuron projection development (GO:0031175), melanosome organization (GO:0032438), regulation of Cdc42 protein signal transduction (GO:0032489), positive regulation of low-density lipoprotein particle receptor catabolic process (GO:0032805), cholesterol efflux (GO:0033344), phospholipid efflux (GO:0033700), very-low-density lipoprotein particle remodeling (GO:0034372), low-density lipoprotein particle remodeling (GO:0034374), high-density lipoprotein particle remodeling (GO:0034375), high-density lipoprotein particle assembly (GO:0034380), chylomicron remnant clearance (GO:0034382), high-density lipoprotein particle clearance (GO:0034384), very-low-density lipoprotein particle clearance (GO:0034447), locomotory exploration behavior (GO:0035641)

GO Molecular Function (23): amyloid-beta binding (GO:0001540), signaling receptor binding (GO:0005102), structural molecule activity (GO:0005198), lipid carrier activity (GO:0005319), phospholipid binding (GO:0005543), heparin binding (GO:0008201), lipid binding (GO:0008289), antioxidant activity (GO:0016209), enzyme binding (GO:0019899), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), heparan sulfate proteoglycan binding (GO:0043395), protein-containing complex binding (GO:0044877), metal chelating activity (GO:0046911), protein dimerization activity (GO:0046983), receptor ligand activity (GO:0048018), tau protein binding (GO:0048156), low-density lipoprotein particle receptor binding (GO:0050750), phosphatidylcholine-sterol O-acyltransferase activator activity (GO:0060228), very-low-density lipoprotein particle receptor binding (GO:0070326), lipoprotein particle binding (GO:0071813), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515)

GO Cellular Component (32): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), clathrin-coated endocytic vesicle membrane (GO:0030669), extracellular matrix (GO:0031012), chylomicron remnant (GO:0034360), very-low-density lipoprotein particle (GO:0034361), low-density lipoprotein particle (GO:0034362), intermediate-density lipoprotein particle (GO:0034363), high-density lipoprotein particle (GO:0034364), discoidal high-density lipoprotein particle (GO:0034365), melanosome (GO:0042470), chylomicron (GO:0042627), neuronal cell body (GO:0043025), synaptic cleft (GO:0043083), extracellular exosome (GO:0070062), endocytic vesicle lumen (GO:0071682), blood microparticle (GO:0072562), multivesicular body, internal vesicle (GO:0097487), glutamatergic synapse (GO:0098978), extracellular vesicle (GO:1903561), lipoprotein particle (GO:1990777), endosome (GO:0005768), multivesicular body (GO:0005771)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Metabolism of proteins	2
Plasma lipoprotein remodeling	2
Signaling by ERBB4	1
Binding and Uptake of Ligands by Scavenger Receptors	1
Generic Transcription Pathway	1
Post-translational protein modification	1
Plasma lipoprotein assembly	1
Plasma lipoprotein clearance	1
NR1H2 and NR1H3-mediated signaling	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Signaling by Receptor Tyrosine Kinases	1
Transport of small molecules	1
Metabolism	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
cellular anatomical structure	3
intracellular membrane-bounded organelle	3
signal transduction	2
molecular_function	2
binding	2
lipoprotein particle receptor binding	2
cytoplasm	2
endomembrane system	2
triglyceride-rich plasma lipoprotein particle	2
plasma lipoprotein particle	2
response to oxidative stress	1
response to oxygen-containing compound	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
response to nutrient levels	1
energy homeostasis	1
acylglycerol metabolic process	1
cholesterol metabolic process	1
sterol catabolic process	1
alcohol catabolic process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
endocytosis	1
organelle organization	1
G protein-coupled receptor activity	1
chemical synaptic transmission	1
memory	1
sterol metabolic process	1
secondary alcohol metabolic process	1
macromolecule biosynthetic process	1
regulation of platelet activation	1
platelet activation	1
negative regulation of blood coagulation	1
negative regulation of cell activation	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
gene expression	1

Protein interactions and networks

STRING

6284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOE	APOB	P04114	999
APOE	APOA1	P02647	999
APOE	APP	P05067	999
APOE	APOC3	P02656	998
APOE	APOA2	P02652	998
APOE	APOC2	P02655	998
APOE	CLU	P10909	998
APOE	LRP1	Q07954	997
APOE	VLDLR	P98155	997
APOE	LRP8	Q14114	997
APOE	APOC1	P02654	996
APOE	SORL1	Q92673	995
APOE	TREM2	Q9NZC2	994
APOE	VTN	P01141	989
APOE	LRP2	P98164	988

IntAct

293 interactions, top by confidence:

A	B	Type	Score
SNCA	APOE	psi-mi:“MI:0915”(physical association)	0.810
SNCA	APOE	psi-mi:“MI:0403”(colocalization)	0.810
SNCA	APOE	psi-mi:“MI:0407”(direct interaction)	0.810
LRP1	APOE	psi-mi:“MI:0407”(direct interaction)	0.780
APOE	LRP1	psi-mi:“MI:0914”(association)	0.780
APOE	LRP1	psi-mi:“MI:0915”(physical association)	0.780
APOE	LRP1	psi-mi:“MI:0407”(direct interaction)	0.780
LRP1	APOE	psi-mi:“MI:0915”(physical association)	0.780
APP	APOE	psi-mi:“MI:0407”(direct interaction)	0.750
APOE	APP	psi-mi:“MI:0915”(physical association)	0.750
	APOE	psi-mi:“MI:0407”(direct interaction)	0.730

BioGRID (216): APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), APOE (Affinity Capture-MS), RPL4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D9S1R0, A0A2Y9GHM3, G5CBM7, P02649, P05770, P0DKU9, P0DKW5, P0DKW6, P0DKW7, P0DKW8, P0DKY2, P0DML7, P0DML8, P0DML9, P0DMM0, P0DMM1, P0DN41, P0DO94, P0DO95, P0DOA3, P0DOC3, P0DSE0, P0DTR8, P0DTT1, P0DTT2, P0DUI5, P0DUI6, P0DUI7, P0DUI8, P0DUI9, P0DUJ0, P0DUY4, P0DUY6, P0DUY7, P0DUY8, P0DUZ0, P0DUZ1, P0DUZ2, P0DUZ6, P0DUZ7

Diamond homologs: A0A0D9S1R0, A0A2Y9GHM3, A0A6P3R0Z0, A0A6P6DKR7, G5CBM7, L5KM50, P02649, P02650, P05770, P08226, P0DKU9, P0DKW5, P0DKW6, P0DKW7, P0DKW8, P0DKY2, P0DML7, P0DML8, P0DML9, P0DMM0, P0DMM1, P0DN38, P0DN39, P0DN41, P0DO94, P0DO95, P0DOA3, P0DOC3, P0DSE0, P0DTR8, P0DTT1, P0DTT2, P0DUI5, P0DUI6, P0DUI7, P0DUI8, P0DUI9, P0DUJ0, P0DUJ2, P0DUP7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
APOE	up-regulates	VLDLR	binding
APOE	up-regulates	SORL1	binding
APOA1	“up-regulates activity”	APOE	relocalization
SRSF11	“up-regulates quantity by stabilization”	APOE	“post transcriptional regulation”
APOE	“up-regulates activity”	MAPT	binding
SORT1	“up-regulates quantity”	APOE	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Visual phototransduction	5	21.3×	6e-04
SUMOylation of transcription cofactors	5	19.9×	6e-04
Response to elevated platelet cytosolic Ca2+	5	13.4×	1e-03
Post-translational protein phosphorylation	6	9.8×	1e-03
Platelet activation, signaling and aggregation	5	8.7×	6e-03
Platelet degranulation	6	8.6×	2e-03
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	6	8.5×	2e-03
Sensory Perception	5	7.8×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	6	26.3×	8e-05
negative regulation of gene expression	9	8.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

274 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	8
Uncertain significance	116
Likely benign	107
Benign	4

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
126456	NM_000041.4(APOE):c.497TCC[1] (p.Leu167del)	Pathogenic
17849	NM_000041.4(APOE):c.61G>A (p.Glu21Lys)	Pathogenic
17852	NM_000041.4(APOE):c.237-2A>G	Pathogenic
17853	NM_000041.4(APOE):c.415_435dup (p.Glu139_Gly145dup)	Pathogenic
17857	NM_000041.4(APOE):c.490A>G (p.Lys164Glu)	Pathogenic
17858	NM_000041.4(APOE):c.490A>C (p.Lys164Gln)	Pathogenic
17859	NM_000041.4(APOE):c.736C>T (p.Arg246Cys)	Pathogenic
17861	NM_000041.4(APOE):c.146del (p.Gly49fs)	Pathogenic
17874	NM_000041.4(APOE):c.455G>A (p.Arg152Gln)	Pathogenic
17875	NM_000041.4(APOE):c.875G>A (p.Arg292His)	Pathogenic
17879	NM_000041.4(APOE):c.488G>C (p.Arg163Pro)	Pathogenic
1077013	NM_000041.4(APOE):c.494G>C (p.Arg165Pro)	Likely pathogenic
1341575	NM_000041.4(APOE):c.548G>C (p.Gly183Ala)	Likely pathogenic
17850	NM_000041.4(APOE):c.460C>A (p.Arg154Ser)	Likely pathogenic
17862	NM_000041.4(APOE):c.683G>A (p.Trp228Ter)	Likely pathogenic
375636	NM_000041.4(APOE):c.461G>T (p.Arg154Leu)	Likely pathogenic
4293233	NM_000041.4(APOE):c.461G>A (p.Arg154His)	Likely pathogenic
4812829	NM_000041.4(APOE):c.300_303del (p.Thr101fs)	Likely pathogenic
487346	NM_000041.4(APOE):c.478C>T (p.Arg160Cys)	Likely pathogenic

SpliceAI

450 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44906600:A:AG	acceptor_gain	1.0000
19:44906601:G:GG	acceptor_gain	1.0000
19:44906601:GACT:G	acceptor_gain	1.0000
19:44907754:A:AG	acceptor_gain	1.0000
19:44907755:C:G	acceptor_gain	1.0000
19:44907755:CACA:C	acceptor_loss	1.0000
19:44907756:A:AG	acceptor_gain	1.0000
19:44907756:ACAG:A	acceptor_gain	1.0000
19:44907757:C:G	acceptor_gain	1.0000
19:44907757:CA:C	acceptor_loss	1.0000
19:44907758:A:AG	acceptor_gain	1.0000
19:44907758:A:T	acceptor_loss	1.0000
19:44907758:AG:A	acceptor_gain	1.0000
19:44907758:AGGAT:A	acceptor_gain	1.0000
19:44907759:G:GC	acceptor_gain	1.0000
19:44907759:GG:G	acceptor_gain	1.0000
19:44907759:GGA:G	acceptor_gain	1.0000
19:44907759:GGAT:G	acceptor_gain	1.0000
19:44907759:GGATG:G	acceptor_gain	1.0000
19:44907949:TGAG:T	donor_gain	1.0000
19:44907950:GAG:G	donor_gain	1.0000
19:44907950:GAGG:G	donor_gain	1.0000
19:44907951:AG:A	donor_gain	1.0000
19:44907952:GG:G	donor_gain	1.0000
19:44907953:G:GG	donor_gain	1.0000
19:44908524:C:A	acceptor_gain	1.0000
19:44908529:GCAG:G	acceptor_loss	1.0000
19:44908530:CAG:C	acceptor_loss	1.0000
19:44908531:A:AG	acceptor_gain	1.0000
19:44908531:AG:A	acceptor_gain	1.0000

AlphaMissense

2023 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44908788:G:C	K164N	0.956
19:44908788:G:T	K164N	0.956
19:44907848:G:C	W44C	0.953
19:44907848:G:T	W44C	0.953
19:44909176:T:A	W294R	0.952
19:44909176:T:C	W294R	0.952
19:44909143:T:C	F283L	0.950
19:44909145:C:A	F283L	0.950
19:44909145:C:G	F283L	0.950
19:44908648:G:C	A118P	0.940
19:44908779:G:C	K161N	0.930
19:44908779:G:T	K161N	0.930
19:44908834:T:G	Y180D	0.928
19:44908802:A:T	D169V	0.925
19:44908777:A:G	K161E	0.920
19:44907949:T:C	L78P	0.918
19:44908814:T:C	L173P	0.917
19:44908781:T:C	L162P	0.914
19:44909132:T:C	L279P	0.912
19:44908802:A:C	D169A	0.911
19:44909144:T:C	F283S	0.908
19:44908804:G:C	A170P	0.905
19:44908702:T:G	Y136D	0.904
19:44908793:T:C	L166P	0.904
19:44908801:G:C	D169H	0.904
19:44909178:G:C	W294C	0.902
19:44909178:G:T	W294C	0.902
19:44908786:A:G	K164E	0.901
19:44908790:G:C	R165P	0.899
19:44907901:C:T	S62F	0.895

dbSNP variants (sampled 300 via entrez): RS1000537350 (19:44905045 C>T), RS1000591062 (19:44904847 A>C), RS1002111557 (19:44905500 G>A), RS1003046280 (19:44906148 A>G), RS1003367097 (19:44909068 C>G,T), RS1003676198 (19:44904590 A>C), RS1004131587 (19:44905248 C>A), RS1005580324 (19:44904530 C>G,T), RS1006208806 (19:44904296 T>C), RS1006341624 (19:44904373 C>G), RS1006701078 (19:44904218 C>G,T), RS1006903010 (19:44909824 A>G), RS1006923620 (19:44903919 C>G,T), RS1007216891 (19:44906752 C>A,T), RS1007705570 (19:44905230 G>A)

Disease associations

OMIM: gene MIM:107741 | disease phenotypes: MIM:611771, MIM:104310, MIM:269600, MIM:603075, MIM:606889, MIM:607822, MIM:617347, MIM:143890, MIM:122700, MIM:608516

GenCC curated gene-disease

Disease	Classification	Inheritance
Alzheimer disease 2	Definitive	Autosomal dominant
lipoprotein glomerulopathy	Strong	Autosomal dominant
hyperlipoproteinemia type 3	Strong	Autosomal dominant
sea-blue histiocyte syndrome	Supportive	Autosomal dominant

Mondo (13): lipoprotein glomerulopathy (MONDO:0012725), Alzheimer disease 2 (MONDO:0007089), sea-blue histiocyte syndrome (MONDO:0010017), age related macular degeneration 1 (MONDO:0011285), Alzheimer disease 4 (MONDO:0011743), Alzheimer disease 3 (MONDO:0011913), hyperlipoproteinemia type 3 (MONDO:0018473), familial hypercholesterolemia (MONDO:0005439), coumarin resistance (MONDO:0007390), Alzheimer disease (MONDO:0004975), coronary artery disease, severe, susceptibility to (MONDO:0800425), major depressive disorder (MONDO:0002009), hyperlipoproteinemia (MONDO:0037748)

Orphanet (5): Lipoprotein glomerulopathy (Orphanet:329481), Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), OBSOLETE: Sea-blue histiocytosis (Orphanet:158029), Dysbetalipoproteinemia (Orphanet:412), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000529	Progressive visual loss
HP:0000608	Macular degeneration
HP:0000660	Lipemia retinalis
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0000799	Renal steatosis
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000951	Abnormality of the skin
HP:0001013	Eruptive xanthomas
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001285	Spastic tetraparesis
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001394	Cirrhosis
HP:0001397	Hepatic steatosis
HP:0001513	Obesity
HP:0001681	Angina pectoris

GWAS associations

403 associations (top):

Study	Trait	p-value
GCST000018_1	Alzheimer’s disease (late onset)	1.000000e-39
GCST000121_1	Alzheimer’s disease	1.000000e-39
GCST000124_1	Alzheimer’s disease	2.000000e-44
GCST000132_2	LDL cholesterol	3.000000e-43
GCST000134_3	LDL cholesterol	1.000000e-60
GCST000178_6	C-reactive protein	9.000000e-21
GCST000179_2	C-reactive protein	1.000000e-07
GCST000234_2	LDL cholesterol	2.000000e-07
GCST000237_1	Alzheimer’s disease	6.000000e-14
GCST000282_9	LDL cholesterol	2.000000e-19
GCST000285_7	Cholesterol, total	3.000000e-19
GCST000287_9	LDL cholesterol	4.000000e-27
GCST000288_4	HDL cholesterol	4.000000e-07
GCST000289_3	Triglycerides	2.000000e-09
GCST000313_1	Alzheimer’s disease	1.000000e-40
GCST000337_15	Quantitative traits	5.000000e-06
GCST000337_19	Quantitative traits	3.000000e-07
GCST000337_29	Quantitative traits	2.000000e-06
GCST000430_5	C-reactive protein	5.000000e-27
GCST000479_3	Alzheimer’s disease	2.000000e-157
GCST000480_3	Alzheimer’s disease	2.000000e-16
GCST000484_5	Alzheimer’s disease	3.000000e-11
GCST000573_11	Brain imaging	1.000000e-09
GCST000573_5	Brain imaging	1.000000e-07
GCST000682_1	Alzheimer’s disease	1.000000e-295
GCST000755_36	HDL cholesterol	4.000000e-21
GCST000758_6	Triglycerides	1.000000e-30
GCST000759_24	LDL cholesterol	9.000000e-147
GCST000760_49	Cholesterol, total	5.000000e-111
GCST000807_5	LDL cholesterol	2.000000e-40

EFO canonical traits (80, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004458	C-reactive protein measurement
EFO:0004574	total cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0004847	age at onset
EFO:0005940	psychotic symptoms
EFO:0004362	psychomotor performance
EFO:0004529	lipid measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0000195	metabolic syndrome
EFO:0005039	hippocampal atrophy
EFO:0004723	coronary artery calcification
EFO:0004732	lipoprotein measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0005194	amyloid-beta measurement
EFO:0006799	Lewy body dementia measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0004874	memory performance
EFO:0006806	paragraph delayed recall measurement
EFO:0006805	word list delayed recall measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:1001492	atrophic macular degeneration
EFO:0007653	clinical ideal cardiovascular health
EFO:0007800	body fat percentage
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100
D003865	Depressive Disorder, Major	F03.600.300.375
D006951	Hyperlipoproteinemias	C18.452.584.500.500.644
D012618	Sea-Blue Histiocyte Syndrome	C10.228.140.163.100.435.825.775; C15.604.250.410.800; C16.320.565.189.435.825.775; C16.320.565.398.641.803.850; C16.320.565.595.554.825.775; C18.452.132.100.435.825.775; C18.452.584.563.641.803.850; C18.452.648.189.435.825.775; C18.452.648.398.641.803.850; C18.452.648.595.554.825.775
C536595	Alzheimer disease type 2 (supp.)
C536596	Alzheimer disease type 4 (supp.)
C536598	Alzheimer disease, familial, type 3 (supp.)
C563039	Coumarin Resistance (supp.)
C567089	Lipoprotein Glomerulopathy (supp.)
C566411	Macular Degeneration, Age-Related, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

12 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs429358	Toxicity	3	acenocoumarol;warfarin	Hemorrhage;Venous thromboembolism
rs429358	Toxicity	3	Antivirals for treatment of HIV infections;combinations;ritonavir	HIV infectious disease;Hyperlipidemias
rs429358	Efficacy	3	HMG-CoA reductase inhibitors	Alzheimer Disease
rs429358	Efficacy	3	warfarin
rs429358	Efficacy	3	simvastatin	Myocardial Infarction
rs7412	Efficacy	2B	atorvastatin	Coronary Disease;Hyperlipidemias
rs7412	Toxicity	3	Antivirals for treatment of HIV infections;combinations;ritonavir	HIV infectious disease;Hypertriglyceridemia
rs7412	Toxicity	3	Antivirals for treatment of HIV infections;combinations;ritonavir	HIV infectious disease;Hyperlipidemias;Hypertriglyceridemia
rs7412	Efficacy	3	pravastatin
rs7412	Efficacy	3	fluvastatin
rs7412	Efficacy	3	fenofibrate	Hypertriglyceridemia
rs7412	Efficacy	3	warfarin

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7412	APOC1, APOE	2B	12.50	7	Antivirals for treatment of HIV infections;combinations;ritonavir;fluvastatin;atorvastatin;pravastatin;fenofibrate;warfarin
rs429358	APOC1, APOE, TOMM40	3	3.00	5	acenocoumarol;warfarin;simvastatin;Antivirals for treatment of HIV infections;combinations;ritonavir;warfarin;HMG-CoA reductase inhibitors
rs445925	APOC1, APOE	3	1.25	1	HMG-CoA reductase inhibitors
rs71352238	APOE, TOMM40		0.00	0
rs449647	APOE		0.00	0
rs405509	APOE		0.00	0
rs769450	APOE		0.00	0

CTD chemical–gene interactions

145 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Warfarin	affects response to substance	8
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	affects methylation, decreases expression, increases expression	4
Air Pollutants	affects response to substance, decreases expression, increases abundance, increases expression	4
Chlorpyrifos	affects response to substance, affects expression, decreases reaction, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Cyclosporine	decreases expression	4
Simvastatin	affects response to substance, decreases expression	4
perfluorooctanoic acid	decreases expression, increases expression	3
Benzo(a)pyrene	increases methylation, decreases expression, decreases methylation	3
Cadmium	decreases abundance, decreases expression, increases expression, increases response to substance, affects binding (+2 more)	3
Nickel	affects binding, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects response to substance	3
perfluorooctane sulfonic acid	decreases expression	2
entinostat	increases expression, affects cotreatment	2
GW 3965	increases expression, increases secretion	2
bisphenol S	increases expression	2
Valsartan	decreases reaction, affects cotreatment, decreases expression	2
Atorvastatin	decreases expression, affects cotreatment	2
Rosiglitazone	affects response to substance, increases expression	2
Resveratrol	affects secretion, increases expression	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Fluvastatin	affects cotreatment, affects response to substance, increases expression	2
Arsenic	increases abundance, increases response to substance	2
Aspirin	affects response to substance, decreases reaction, increases abundance, increases reaction	2
Bezafibrate	affects cotreatment, decreases expression, increases expression	2
Cisplatin	decreases response to substance, affects cotreatment, decreases expression	2
Cholesterol, HDL	affects abundance, increases abundance	2
Mercury	affects response to substance	2

Cellosaurus cell lines

113 cell lines: 87 induced pluripotent stem cell, 13 transformed cell line, 10 finite cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0J87	AG05810	Finite cell line	Female
CVCL_0J92	AG06868	Transformed cell line	Female
CVCL_0J93	AG06869	Finite cell line	Female
CVCL_2Y81	AG21158	Finite cell line	Female
CVCL_2Y82	AG21159	Transformed cell line	Female
CVCL_4K35	AG08242	Transformed cell line	Male
CVCL_4K36	AG08243	Finite cell line	Male
CVCL_4K61	AG08509	Finite cell line	Male
CVCL_4L97	AG09714	Transformed cell line	Female
CVCL_4M06	AG09952	Transformed cell line	Male

Clinical trials (associated diseases)

154 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03811223	PHASE4	UNKNOWN	Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia
NCT07403825	PHASE4	RECRUITING	Efficacy of Faricimab in Patients With Subretinal Hyper-reflective Material
NCT04520308	PHASE4	UNKNOWN	An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis
NCT05969054	PHASE4	UNKNOWN	Improvement Effect of Lacosamide and Levetiracetam on Cognitive in Alzheimer’s Disease Patients With Epilepsy
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00145431	PHASE3	TERMINATED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Subjects With A Genetic Cholesterol Disorder.
NCT00214604	PHASE3	COMPLETED	Type III Dysbetalipoproteinemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT03806478	PHASE2	UNKNOWN	Study of APH-1105 in Patients With Mild to Moderate Alzheimer’s Disease
NCT04838301	PHASE2	RECRUITING	Allopregnanolone Regenerative Therapeutic for Mild Alzheimer’s Disease
NCT02684578	PHASE2	COMPLETED	Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD
NCT03038880	PHASE2	COMPLETED	Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
NCT03972709	PHASE2	TERMINATED	A Study Assessing the Safety, Tolerability, and Efficacy of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)
NCT04607148	PHASE2	TERMINATED	A Study Assessing the Long-Term Safety and Tolerability of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration
NCT06722157	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy
NCT02380573	PHASE2	COMPLETED	Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer’s Disease
NCT07011706	PHASE2	ACTIVE_NOT_RECRUITING	ATI-045 Versus Placebo in Patients With Moderate-to-Severe Atopic Dermatitis
NCT07252440	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of TTYP01 Tablets in Early Symptomatic Alzheimer’s Disease
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy