APOE
apolipoprotein E, the group of Apolipoproteins
Basic information
Region (hg38): 19:44905791-44909393
Previous symbols: [ "AD2" ]
Links
Phenotypes
GenCC
Source:
- hyperlipoproteinemia type 3 (Strong), mode of inheritance: AD
- lipoprotein glomerulopathy (Strong), mode of inheritance: AD
- hyperlipoproteinemia type 3 (Strong), mode of inheritance: AR
- Alzheimer disease 2 (Definitive), mode of inheritance: AD
- hyperlipoproteinemia type 3 (Moderate), mode of inheritance: AR
- sea-blue histiocyte syndrome (Supportive), mode of inheritance: AD
- lipoprotein glomerulopathy (Supportive), mode of inheritance: AD
- Alzheimer disease 2 (Limited), mode of inheritance: Unknown
- hyperlipoproteinemia type 3 (Strong), mode of inheritance: AD
- hyperlipoproteinemia type 3 (Strong), mode of inheritance: AR
- lipoprotein glomerulopathy (Strong), mode of inheritance: AD
- sea-blue histiocyte syndrome (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperlipoproteinemia, type III; Lipoprotein glomerulopathy; Sea-blue histiocyte disease | AD/AR | Cardiovascular; Gastrointestinal; Renal | In Hyperlipoproteinemia, type III, dietary and medical measures related to treating abnormal lipid profiles (including apharesis in some individuals) can be beneficial, including as relates to the risk of cardiovascular disease; In LPG, early diagnosis may be advantageous in order to allow medical treatment (eg, with fibrate therapy); In Sea-blue histiocyte disease, individuals may present with splenomegaly with sea-blue histiocytes, hypertriglyceridemia, and thrombocytopenia, and preventive measures and surveillance related to cardiac manifestations may be beneficial, and knowledge that splenectomy can exacerbate hypertriglyceridemia may additionally be advantageous | Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Renal | 4242937; 4195998; 6795720; 6289314; 6860421; 6323533; 3721502; 3771793; 3029073; 3038959; 3243553; 2539388; 2556398; 2313204; 2341812; 1864973; 1674745; 1713245; 1360898; 1361196; 1356443; 8488843; 7635945; 7586659; 9176854; 11095479; 15630634; 16094309; 16143024; 16431249; 16690468; 18077821; 20534298; 21534236; 22069485; 22481068; 22949395; 28966924; 30421781; 30685233 |
ClinVar
This is a list of variants' phenotypes submitted to
- Sea-blue histiocyte syndrome (1 variants)
- not provided (1 variants)
- Cardiovascular phenotype (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOE gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 64 | 64 | ||||
| missense | 55 | 63 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 2 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 4 | |||||
| Total | 1 | 7 | 60 | 67 | 1 |
Highest pathogenic variant AF is 0.0000263
Variants in APOE
This is a list of pathogenic ClinVar variants found in the APOE region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-44905888-G-A | APOE-related disorder | Uncertain significance (Mar 23, 2023) | ||
| 19-44905910-C-G | not specified | Benign (-) | ||
| 19-44905923-G-A | Alzheimer disease 2 • APOE-related disorder | Uncertain significance (Sep 02, 2020) | ||
| 19-44906322-C-T | Likely benign (Jun 21, 2021) | |||
| 19-44906643-G-C | Cardiovascular phenotype | Uncertain significance (Feb 21, 2024) | ||
| 19-44906646-T-C | Cardiovascular phenotype | Likely benign (May 04, 2020) | ||
| 19-44906655-A-G | Familial type 3 hyperlipoproteinemia;Lipoprotein glomerulopathy | Uncertain significance (Apr 09, 2021) | ||
| 19-44906745-G-A | Benign (Aug 30, 2018) | |||
| 19-44907187-G-A | Warfarin response | drug response (Aug 31, 2010) | ||
| 19-44907777-G-A | HYPERLIPOPROTEINEMIA, TYPE III, AND ATHEROSCLEROSIS ASSOCIATED WITH APOE5 | Pathogenic (Aug 01, 1995) | ||
| 19-44907785-G-A | Cardiovascular phenotype • 7 conditions | Likely benign (Dec 17, 2021) | ||
| 19-44907800-G-A | Cardiovascular phenotype | Likely benign (Dec 22, 2023) | ||
| 19-44907806-C-G | Cardiovascular phenotype | Likely benign (Apr 04, 2022) | ||
| 19-44907807-G-A | APOE5 VARIANT | Likely benign (May 24, 2019) | ||
| 19-44907824-C-G | Likely benign (Jun 15, 2021) | |||
| 19-44907830-G-A | Uncertain significance (Mar 10, 2021) | |||
| 19-44907832-A-G | Cardiovascular phenotype | Uncertain significance (Jan 04, 2024) | ||
| 19-44907836-C-T | Cardiovascular phenotype | Likely benign (Sep 01, 2021) | ||
| 19-44907841-A-C | Cardiovascular phenotype | Uncertain significance (Sep 26, 2022) | ||
| 19-44907843-C-T | Lipoprotein glomerulopathy • 7 conditions | Pathogenic/Likely pathogenic (Feb 24, 2022) | ||
| 19-44907853-T-C | Alzheimer disease 4 • Cardiovascular phenotype | Conflicting classifications of pathogenicity (Jul 01, 2024) | ||
| 19-44907854-G-A | Cardiovascular phenotype | Likely benign (Sep 17, 2021) | ||
| 19-44907859-TG-T | Familial type 3 hyperlipoproteinemia | Pathogenic (Sep 01, 1992) | ||
| 19-44907864-C-A | Uncertain significance (Aug 15, 2017) | |||
| 19-44907879-C-T | Cardiovascular phenotype | Likely benign (Dec 25, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| APOE | protein_coding | protein_coding | ENST00000252486 | 3 | 3640 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00187 | 0.912 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.740 | 188 | 219 | 0.859 | 0.0000167 | 1958 |
| Missense in Polyphen | 64 | 83.541 | 0.76609 | 681 | ||
| Synonymous | 1.04 | 87 | 100 | 0.868 | 0.00000788 | 658 |
| Loss of Function | 1.49 | 6 | 11.5 | 0.524 | 5.01e-7 | 115 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000362 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues. {ECO:0000303|PubMed:3283935}.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:8287539}. Note=The disease is caused by mutations affecting the gene represented in this entry. The vast majority of the patients are homozygous for APOE*2 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 APOE*4 variant are at higher risk of CAD.; DISEASE: 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. {ECO:0000269|PubMed:8346443}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The APOE*4 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 APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known. {ECO:0000269|PubMed:8346443}.; DISEASE: 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. {ECO:0000269|PubMed:11095479, ECO:0000269|PubMed:16094309}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Familial hypercholesterolemia (FH) [MIM:143890]: A common autosomal dominant disorder characterized by elevated serum low- density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. The disorder occurs in 2 clinical forms: a mild form that becomes evident in the fourth or fifth decade in individuals carrying heterozygous LDLR mutations; a more severe form that usually manifests in the first two decades of life in individuals with homozygous LDLR mutations. {ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230, ECO:0000269|PubMed:26802169}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
- Pathway
- Alzheimer,s disease - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Vitamin B12 Metabolism;Alzheimers Disease;Apoptosis-related network due to altered Notch3 in ovarian cancer;ApoE and miR-146 in inflammation and atherosclerosis;HDAC6 interactions;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Statin Pathway;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Gene expression (Transcription);Chylomicron assembly;Vesicle-mediated transport;Plasma lipoprotein assembly;Generic Transcription Pathway;Chylomicron remodeling;Post-translational protein phosphorylation;HDL remodeling;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Chylomicron clearance;Metabolism;Plasma lipoprotein clearance;Transport of small molecules;Metabolism of vitamins and cofactors;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Plasma lipoprotein assembly, remodeling, and clearance;Retinoid metabolism and transport;G alpha (i) signalling events;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Plasma lipoprotein remodeling;Visual phototransduction;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors;GPCR downstream signalling
(Consensus)
Recessive Scores
- pRec
- 0.998
Haploinsufficiency Scores
- pHI
- 0.275
- hipred
- N
- hipred_score
- 0.461
- ghis
- 0.418
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.767
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Apoe
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; taste/olfaction phenotype; muscle phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- apoea
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- response to reactive oxygen species;retinoid metabolic process;negative regulation of endothelial cell proliferation;response to dietary excess;regulation of transcription by RNA polymerase II;triglyceride metabolic process;cholesterol biosynthetic process;cholesterol catabolic process;cellular calcium ion homeostasis;receptor-mediated endocytosis;cytoskeleton organization;G protein-coupled receptor signaling pathway;nitric oxide mediated signal transduction;synaptic transmission, cholinergic;long-term memory;cholesterol metabolic process;negative regulation of platelet activation;negative regulation of gene expression;positive regulation of cholesterol esterification;positive regulation of cholesterol efflux;lipid transport involved in lipid storage;positive regulation of neuron projection development;negative regulation of neuron projection development;long-chain fatty acid transport;protein import;virion assembly;triglyceride catabolic process;cGMP-mediated signaling;negative regulation of blood coagulation;regulation of axon extension;neuron projection development;negative regulation of cellular protein metabolic process;regulation of cholesterol transport;regulation of protein homooligomerization;regulation of Cdc42 protein signal transduction;positive regulation of low-density lipoprotein particle receptor catabolic process;cholesterol efflux;phospholipid efflux;chylomicron remodeling;very-low-density lipoprotein particle remodeling;low-density lipoprotein particle remodeling;high-density lipoprotein particle remodeling;chylomicron assembly;high-density lipoprotein particle assembly;chylomicron remnant clearance;high-density lipoprotein particle clearance;very-low-density lipoprotein particle clearance;locomotory exploration behavior;lipoprotein metabolic process;lipoprotein biosynthetic process;lipoprotein catabolic process;vasodilation;cholesterol homeostasis;amyloid precursor protein metabolic process;negative regulation of MAP kinase activity;negative regulation of neuron apoptotic process;negative regulation of blood vessel endothelial cell migration;post-translational protein modification;reverse cholesterol transport;cellular protein metabolic process;positive regulation by host of viral process;regulation of innate immune response;negative regulation of cholesterol biosynthetic process;positive regulation of endocytosis;positive regulation of transcription, DNA-templated;positive regulation of lipid biosynthetic process;intracellular transport;regulation of neuronal synaptic plasticity;artery morphogenesis;negative regulation of inflammatory response;positive regulation of nitric-oxide synthase activity;positive regulation of membrane protein ectodomain proteolysis;regulation of protein metabolic process;maintenance of location in cell;fatty acid homeostasis;positive regulation of dendritic spine development;regulation of proteasomal protein catabolic process;response to caloric restriction;triglyceride homeostasis;positive regulation of ERK1 and ERK2 cascade;triglyceride-rich lipoprotein particle clearance;intermediate-density lipoprotein particle clearance;negative regulation of canonical Wnt signaling pathway;regulation of cholesterol metabolic process;negative regulation of triglyceride metabolic process;AMPA glutamate receptor clustering;NMDA glutamate receptor clustering;cellular oxidant detoxification;regulation of amyloid-beta clearance;negative regulation of long-term synaptic potentiation;negative regulation of neuron death;positive regulation of postsynaptic membrane organization;negative regulation of presynaptic membrane organization;negative regulation of amyloid-beta formation;positive regulation of dendritic spine maintenance;positive regulation of phospholipid efflux;positive regulation of lipid transport across blood-brain barrier;positive regulation of heparan sulfate binding;positive regulation of heparan sulfate proteoglycan binding;regulation of cellular response to very-low-density lipoprotein particle stimulus;regulation of amyloid fibril formation;positive regulation of amyloid fibril formation;regulation of behavioral fear response
- Cellular component
- extracellular region;extracellular space;nucleus;cytoplasm;early endosome;endoplasmic reticulum;endoplasmic reticulum lumen;Golgi apparatus;plasma membrane;membrane;dendrite;clathrin-coated endocytic vesicle membrane;extracellular matrix;very-low-density lipoprotein particle;low-density lipoprotein particle;intermediate-density lipoprotein particle;high-density lipoprotein particle;discoidal high-density lipoprotein particle;chylomicron;neuronal cell body;synaptic cleft;collagen-containing extracellular matrix;extracellular exosome;endocytic vesicle lumen;blood microparticle;glutamatergic synapse;extracellular vesicle;lipoprotein particle
- Molecular function
- amyloid-beta binding;structural molecule activity;lipid transporter activity;protein binding;phospholipid binding;heparin binding;lipid binding;cholesterol binding;antioxidant activity;cholesterol transporter activity;identical protein binding;protein homodimerization activity;heparan sulfate proteoglycan binding;protein-containing complex binding;metal chelating activity;protein dimerization activity;tau protein binding;low-density lipoprotein particle receptor binding;phosphatidylcholine-sterol O-acyltransferase activator activity;very-low-density lipoprotein particle receptor binding;lipoprotein particle binding