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FLASH GENE
Symbol ABCA1 contributors: mct/shn - updated : 29-08-2018
HGNC name ATP-binding cassette, sub-family A (ABC1), member 1
HGNC id 29
Corresponding disease
HDLD familial hypoalphalipoproteinemia
HDLDT1 Tangier disease
Location 9q31.1      Physical location : 107.543.284 - 107.690.436
Synonym name
  • cholesterol efflux regulatory protein
  • high density lipoprotein deficiency, Tangier type, 1
  • ATP-binding cassette sub-family A member 1
  • ATP-binding cassette transporter A1
  • ATP-binding cassette transporter 1
  • ATP-binding cassette 1
  • membrane-bound
  • Tangier disease
  • Synonym symbol(s) ABC1, TGD, CERP, MGC164864, MGC165011, FLJ14958, HDLDT1
    DNA
    TYPE functioning gene
    STRUCTURE 96.81 kb     50 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site
    motif repetitive sequence   ALU   other
    text structure
  • numerous SP1 and putative sterol regulatory elements
  • binding sites for NFKB and activator proteins, conserved non coding sequences
  • sixty-two repetitive Alu sequences were identified in introns 1-49 (
  • transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp (
  • the promoter fragment -200 to -80 bp contains binding motifs for SP1, SP3, E-box, and AP1 (
  • MAPPING cloned Y linked N status confirmed
    Map cen - D9S277 - D9S938 - ABCA1 - D9S1866 - D9S1784 - qter
    Physical map
    SMC2L1 9q31.2 SMC2 structural maintenance of chromosomes 2-like 1 (yeast) LOC347281 9q31.3 similar to hypothetical protein LOC138805 9q31.3 similar to Olfactory receptor 13F1 LOC138804 9q31.3 similar to Olfactory receptor 13C4 LOC138803 9q31.3 similar to Olfactory receptor 13C3 LOC138802 9q31.3 similar to Olfactory receptor 13C8 LOC392375 9 similar to olfactory receptor LOC138799 9q31.3 similar to Olfactory receptor 13C5 LOC392376 9 similar to Olfactory receptor 13C2 LOC286362 9q31.3 similar to Olfactory receptor 13C9 LOC392377 9 similar to olfactory receptor LOC286365 9q31.3 similar to seven transmembrane helix receptor LOC392378 9 similar to Olfactory receptor 13D1 NIPSNAP3A 9q31.3 nipsnap homolog 3A (C. elegans) NIPSNAP3B 9q31.3 nipsnap homolog 3B (C. elegans) ABCA1 9q31.1 ATP-binding cassette, sub-family A (ABC1), member 1 CTL1 CSDUFD1 9q31 cystatin and DUF19 domain containing 1 LOC389779 9 similar to fibronectin type 3 and SPRY (spla, ryanodine) domain containing (with coiled-coil motif) 1; fibronectin type 3 and SPRY domain-containing protein LOC389780 9 similar to KIAA0884 protein LOC389781 9 similar to tuberin-like protein 1; tulip 1 protein; GAP-related interacting partner to E12 GARNL2 9q31 GTPase activating RANGAP domain-like 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    50 splicing 10412 2217 2261 monocytes - 10092505
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly Homo sapiens
    Digestiveintestinelarge intestinecolon lowly Homo sapiens
     intestinesmall intestine  moderately Homo sapiens
     liver   highly Homo sapiens
     salivary gland   lowly Homo sapiens
     stomach   lowly Homo sapiens
    Endocrineadrenal gland   moderately Homo sapiens
     pancreas   lowly Homo sapiens
     thyroid   lowly Homo sapiens
    Lymphoid/Immunelymph node   lowly Homo sapiens
     spleen   lowly Homo sapiens
     thymus   lowly Homo sapiens
    Nervousbrain   highly Homo sapiens
     braindiencephalonthalamus lowly Homo sapiens
     braindiencephalonamygdala lowly Homo sapiens
     brainbasal nucleicaudate nucleus lowly Homo sapiens
     brainhindbraincerebellum lowly Homo sapiens
     brainforebraincerebral cortex lowly Homo sapiens
     brainforebraincerebral lobefrontal lobelowly Homo sapiens
     brainhindbrainmedulla oblongata lowly Homo sapiens
     brainforebraincerebral lobeoccipital lobemoderately Homo sapiens
     brainbasal nucleiputamen moderately Homo sapiens
     brainmidbrainsubstantia nigra lowly Homo sapiens
     brainforebraincerebral lobetemporal lobelowly Homo sapiens
     spinal cord   lowly Homo sapiens
    Reproductivefemale systembreast  lowly Homo sapiens
     female systemovary  lowly Homo sapiens
     female systembreastmammary gland highly Homo sapiens
     female systemplacenta  highly Homo sapiens
     female systemuterus  lowly Homo sapiens
     male systemprostate  lowly Homo sapiens
     male systemtestis  lowly Homo sapiens
    Respiratorylung   moderately Homo sapiens
     respiratory tract   lowly Homo sapiens
    Urinarybladder   lowly Homo sapiens
     kidney   lowly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  lowly Homo sapiens
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Blood/Hematopoieticmonocyte Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    ReproductiveSertoli cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text fetal brain, heart, kidney, liver,spleen, thymus, lung
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal extracellular domain containing a segment homologous to the autoantigen SSN
  • two ATP binding (NBF) site
  • two transmembrane (2TM) domains (2 x 6 segments) separated by a linker region
  • PEST sequence involved in internalization and cholesterol efflux from late endosomes
  • C-terminal AAs between positions 2225 and 2231 required by HIV1 Nef binding
  • HOMOLOGY
    interspecies ortholog to ABCA1, Pan troglodytes
    ortholog to Abca1, Rattus norvegicus
    ortholog to Abca1, Mus musculus
    Homologene
    FAMILY
  • ATP-binding cassette (ABC) superfamily
  • CATEGORY regulatory , transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • role in membrane lipid transport (
  • a key protein in the cellular lipid removal pathway (
  • ABC transporter, traffic ATPase, facilitator of cellular efflux of cholesterol and phospholipid and key regulator of high density lipoprotein (HDL) metabolism
  • leukocyte factor that controls the recruitment of inflammatory cells and protects against atherosclerosis
  • playing a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages
  • necessary for proper maturation of dense bodies in platelets (
  • plays a critical role in CNS apoE metabolism (
  • STX12, FLOT1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux
  • glial ABCA1 required for cholesterol efflux to apoA-I and plays a key role in facilitating cholesterol efflux to apoE (
  • a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo (
  • secrete several species of sphingomyelin and phosphatidylcholine (
  • regulating MEGF10 (function of MEGF10 is modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7)
  • playing an important role in lipid transport in Sertoli cells and influencing male fertility
  • role in transport of cholesterol and phospholipids to nascent HDL particles and plays a central role in lipoprotein metabolism and macrophage cholesterol homeostasis
  • contributes to transport maternal cholesterol to the developing fetus
  • plays a role in the oligomerization and Golgi exit of caveolin-1 during cholesterol efflux in aortic endothelial cells after HDL stimulation
  • ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis
  • mediates the rate-limiting step in high density lipoprotein (HDL) particle formation
  • critical importance of the rate of flux of cholesterol out of lysosomes in the regulation of ABCA1 expression and HDL particle formation
  • ABCA1 and ABCG1 each make complimentary and important contributions to beta-cell function by maintaining islet cholesterol homeostasis
  • ABCA1 regulates cellular cholesterol at two levels, and cholesterol regulation functions are likely essential for PRKACA activation by ABCA1
  • directly promotes the anti-inflammatory arm of the immune response
  • sterol transporters ABCA1, ABCG5, and ABCG8 may play a role in the pathogenesis of cholesterol-related gallbladder diseases (CAGD)
  • ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane
  • is a key macromolecule facilitating bidirectional sterol movement at the plasma membrane (PM) and ABCA1 controls retrograde sterol transport by modulating a certain clathrin-independent endocytic process
  • novel function of ABCA1 in contributing to macrophage export of cholesterol into the extracellular matrix
  • maintains optimal hepatocyte Plasma membrane (PM) free cholesterol (FC), through intracellular FC trafficking, for efficient insulin signaling 2)
  • membrane transporter that facilitates nascent HDL formation
  • important role for hepatic ABCA1 in regulating secretory trafficking and modulating VLDL expansion during the TG accretion phase of hepatic lipoprotein particle assembly
  • affects placental function via trophoblast and macrophage
  • ABCA1 and ABCG1, are essential for maintaining lipid homeostasis in cells such as macrophages by exporting excess cholesterol to extracellular acceptors
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text
  • a key role in cellular cholesterol and phospholipid traffic (
  • a critical role in HDL cholesterol metabolism
  • PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule Mg(2+)-dependent ATP (
    protein
  • beta2-syntrophin/utrophin complex (
  • apolipoprotein A-I (
  • Fas-associated death domain protein, FADD (
  • Phospholipid lipid transfer protein, PLTP (
  • alpha1-syntrophin and Lin7 (
  • syntaxin 13 and flotillin-1 (
  • beta1-syntrophin (
  • serine palmitoyltransferase, long chain base subunit 1, SPTLC1
  • COP9 signalosome, CSN (
  • modulated caveolin-1 oligomerization and physically interacted with oligomer-caveolin-1
  • NR2H1 directly binds to the C-terminal region of ABCA1 to mediate its post-translational regulation
  • potential role of LIPA as a target to increase ABCA1 expression and HDL formation at the cellular and clinical level
  • 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
  • ABCA1 promotes the secretion of IL10, an anti-inflammatory cytokine critical for inflammation resolution
  • ABCA1 activates PRKACA
  • activation of PRKCH and PLD2 signaling pathway is an important mechanism for regulation of TLR2-induced ABCA1 expression
  • ELAVL1 is a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis
  • ABCA1 mediates unfolding the N terminus of APOA1 on the cell surface, followed by lipidation of APOA1 and release of nascent HDL
  • ARF6-independent endocytic pathways may contribute to ABCA1 recycling and efflux of intracellular cholesterol
  • EEPD1 is a novel NR1H2, NR1H3-regulated gene in macrophages and likely it promotes cellular cholesterol efflux by controlling cellular levels and activity of ABCA1
  • cell & other
    REGULATION
    activated by TSH, that upregulated hepatic ABCA1 to promote the efflux of intercellular cumulative cholesterol, resulting in increased plasma cholesterol
    inhibited by SREBF2 in endothelial cells
    PDGFA in vascular smooth muscle cells
    SPTLC1 (inhibits ABCA1 activity leading to the blockade of the exit of ABCA1 from the endoplasmic reticulum
    repressed by HIV1 Nef (Nef downregulates ABCA1 function by a post-translational mechanism that stimulates ABCA1 degradation but does not require the ability of Nef to bind ABCA1)
    Phosphorylated by protein kinase CK2 (
    Other cholesterol carrying out of the cell for uptake into HDL particles : sterol dependent regulated in monocytes and macrophages
    its expression is regulated primarily by oxysterol-dependent activation of liver X receptors
    ASSOCIATED DISORDERS
    corresponding disease(s) HDLDT1 , HDLD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in atheroma compared with macroscopically intact tissue
    tumoral     --low  
    in breast cancer which seems to be associated with poor prognosis
    constitutional     --over  
    increased ABCA1, ABCG5, and ABCG8 expression in cholesterol-related gallbladder diseases (CAGD)
    constitutional       loss of function
    protects the heart against myocardial infarction-induced injury
    constitutional       loss of function
    decreases platelet reactivity and reduces thromboxane A2 production independently of hematopoietic ABCA1
    Susceptibility
  • to coronary artery disease and atherosclerosis
  • to Alzheimer disease and cerebrovascular disease
  • Variant & Polymorphism SNP , other
  • R219K variant decreased severity of coronary artery
  • disease V825I and M883I associated with coronary artery disease, 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V), influences age of symptom onset (lower) in coronary artery disease patients
  • variant (219K, 883I, and 1587R), or promoter variant (14T) in concert with the APOE4 allele, increasing the risk of Alzheimer
  • associated with intermediate and large drusen and advanced age-related macular degeneration (
  • loss-of-function mutation in ABCA1, present in 1/500 individuals, was associated with low plasma levels of APOE and with high risk of AD and cerebrovascular disease in the general population
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    metabolismlipidcholesterol
    increasing the expression of ABCA1 in placenta and thereby the transfer of cholesterol to Smith–Lemli–Opitz fetuses can potentially mitigate the SLOS phenotype
    ANIMAL & CELL MODELS
  • mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism (
  • Abc1 knockout (-/-) mice revealed an approximately 70% reduction in cholesterol, markedly reduced plasma phospholipids, and an almost complete lack of high density lipoproteins (
  • Abca1-/- mice have greatly decreased apoE levels in both the cortex (80%) and the cerebrospinal fluid (98%) (
  • cerebrospinal fluid from Abca1-/- mice had significantly reduced cholesterol as well as small apoE-containing lipoproteins (
  • Abca1-/- astrocytes secreted lipoprotein particles that had markedly decreased cholesterol and apoE and had smaller apoE-containing particles (
  • in both astrocytes and microglia, ABCA1 deficiency reduces lipid efflux to exogenous apoE (
  • the impaired ability to efflux lipids in ABCA1-/- glia results in lipid accumulation in both astrocytes and microglia and apoE secretion is compromised in ABCA1-/- astrocytes and microglia (
  • total plasma cholesterol was significantly reduced by approximately 30% in mice that lack ABCA1 exclusively in the intestine because of a significant reduction in plasma HDL cholesterol (
  • apoA-I, apoA-II, and apoB were significantly decreased in mice that lack ABCA1 exclusively in the intestine (
  • mice lacking both intestinal and hepatic ABCA1 displayed a further significant decrease in plasma HDL cholesterol levels (
  • Mice deficient in displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin(-)Sca-1(+)Kit+ (LSK) in the bone marrow (
  • platelets in Abca1-deficient mice are slightly larger in size and exhibit aggregation and secretion defects in response to low concentrations of thrombin and collagen