APOE

Highest pathogenic variant AF is 0.00006327064

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000252486

Coding exons

3

Length

3640

Individuals with no LoFs

125740

Homozygous LoFs

0

Heterozygous LoFs

8

Defined

125748

p

0.0000318

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.;