Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol APOE contributors: mct/pgu - updated : 17-05-2017
HGNC name apolipoprotein E
HGNC id 613
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly Homo sapiens
Endocrineadrenal gland   highly
Lymphoid/Immunespleen   moderately
Nervousbrain   predominantly Homo sapiens
Reproductivefemale systemovary  moderately
Respiratorylung   moderately
Urinarykidney   highly
Visualeyeretina  moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningretinal pigment epithelium (RPE)  
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage Homo sapiens
Nervousastrocyte Homo sapiens
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal domain of interaction with the LDL receptor and heparin sulfate proteoglycan
  • a hinge region from the C-terminal lipid binding domain
  • an heparin binding region
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Apoe (71.34 pc)
    homolog to murine Apoe (73.70 pc)
    intraspecies homolog to APOA4
    Homologene
    FAMILY
  • APOA1/APOA4/APOE family
  • CATEGORY receptor membrane , transport carrier
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • clearance of chylomicrons, remnants and beta-VLDL from the plasma
  • modulates glutamate receptor function and synaptic plasticity by regulating apoE receptor recycling in neurons, with APOE3 stimulating and APOE4 inhibiting this process
  • in the nervous system, functions as a major carrier and distributor of cholesterol and other lipids, which are essential components of neuronal membranes and myelin sheaths
  • is required for maintenance of the dentate gyrus neural progenitor pool
  • APOE-induced intracellular APP degradation is mediated by the cholesterol efflux function of APOE, which lowers cellular cholesterol levels and subsequently facilitates the intracellular trafficking of APP to lysosomes for degradation
  • plays an important role in lipoprotein metabolism
  • role of APOE and COMT genes in prospective and retrospective memory traits
  • putative functional role of APOE in modulating myelin-related processes in the brain
  • major cholesterol carrier that supports lipid transport and injury repair in the brain
  • influences soluble APP metabolism not through direct binding to soluble APP in solution but through its actions with other interacting receptors/transporters and cell surfaces
  • APOE4 allele drives atrophy to the medial-temporal lobe region in AD
  • has an intrinsic role in pericyte mobility, which is vital in maintaining cerebrovascular function
  • role for APOE in lipid accumulation and adipogenic differentiation in adipose tissue
  • APOE is a critical determinants of brain phospholipid homeostasis and the APOE4 isoform is dysfunctional in this process
  • is an essential anti-atherosclerotic glycoprotein involved in lipid metabolism
  • impaired autophagy may play a role in mediating the pathological effects of APOE4 in AD
  • negative role of the APOE4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling sensory transduction/vision
    fatty acid and sterol
    a component
  • constituent of several lipoproteins including chylomicrons, remnants, VLDL, IDL, some HDLs
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to LDL receptor
  • binding with MYOC promoter SNP (increased intraocular pressure in primary open angle glaucoma
  • binding to heparin
  • APOE4 binds preferentially to very low-density lipoproteins (VLDLs), whereas APOE3 binds preferentially to high-density lipoproteins (HDLs), resulting in different plasma cholesterol levels for the two isoforms
  • APOE associated with APOB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and induction of Sp1 phosphorylation is a mechanism by which APOE upregulates ABCA1 expression
  • mechanistic link between APOE-regulated cholesterol homeostasis and APP degradation
  • APP endocytic trafficking to lysosomes for degradation is a major APP clearance pathway that is differentially regulated by APOE isoforms
  • APOE/PLTP interactions can be modulated by the conformation and lipidation state of APOE
  • APOE regulates the endosomal formation of PMEL amyloid fibrils
  • robust synchronized induction of KLF4 and APOE expression during differentiation of monocytes to macrophages, and KLF4 up-regulates APOE gene in a dose-dependent manner
  • MYLIP is an E3 ubiquitin ligase that targets LDLR for degradation, is a critical determinant of brain APOE metabolism and APP plaque biogenesis
  • SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of APOE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) APOE , ARMDS2 , SBHD , AD2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    APOE4-carriers with dementia of the Alzheimers' type, and memory decline and olfaction, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediodisplay a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions
    constitutional     --low  
    depletion of endogenous APOE in adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation (pMID: 26201081)
    Susceptibility
  • putative susceptibility factor (epsilon 4 allele) for agressive multiple sclerosis
  • susceptibility factor (epsilon 2/3/4 allele) for dementia (in old age)
  • susceptibility for AMD (age related macular dystrophy) (e2/e2 allele increased risk)
  • suceptibility (epsilon 2 allele) to frontotemporal dementia and to myocardial infarction
  • susceptibility to Alzheimer disease 2 (AD2)
  • to ischemic heart disease
  • to cerebral amyloid angiopathy and age-related cognitive decline during normal ageing
  • to Coronary Heart Disease (CHD)
  • Variant & Polymorphism SNP , other
  • (-219G) associated with increased optic nerve damage in primery open angle glaucoma
  • epsilon 2 allele by mother correlated with Smith-Lemli-Opitz severe form
  • ApoE4 mutation was associated with the increased risk of CHD, while ApoE2 allele had a decreased risk of CHD
  • combinations of SNPs in APOE and LPL identify subgroups of individuals at substantially increased risk of ischemic heart disease
  • APOE haplotypes common, found to be significantly associated with AMD, G-G-G-G-epsilon2, T-C-G-G-epsilon3 and T-G-A-G-epsilon4
  • risk estimate of developing AD for individuals with two copies of the apoE4 allele (&
  • 8764;2p100 of the population) is &
    8764;60p100 by the age of 85, and for those with one copy of the apoE4 allele (&
    8764;25p100 of the population) &
    8764;30p100, but the lifetime risk of AD for those with two copies of the apoE3 allele is &
    8764;10p100 by the age of 85
  • APOE4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing
  • Candidate gene
    Marker
  • APOE genotyping may be helpful in diagnosing AD especially in patients presenting with atypical features or early age of onset of dementia
  • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    pharmacological intervention with small molecules that disrupt apoE4 domain interaction is a potential therapeutic approach for apoE4-carrying AD subjects
    ANIMAL & CELL MODELS
  • apoE4 causes age- and Tau-dependent impairment of hilar GABAergic interneurons, leading to learning and memory deficits in mice (
  • young Apoe4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex
  • hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in Vegfa following injury
  • APOE4 reduces evoked hippocampal acetylcholine release in adult mice