GeneBe

ABCA1

protein-coding

ATP binding cassette subfamily A member 1, the group of ATP binding cassette subfamily A

Gene summary

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

Previous symbols:
  • ABC1
  • HDLDT1

MANE transcript

NM_005502.4

Inheritance

AD, AR

ClinVar variants

P:78U:635B:702

Top phenotype

Hypoalphalipoproteinemia, primary, 1; Tangier disease

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr9:104,781,006-104,928,155

External References & Databases

Ensembl (ENSG00000165029)NCBI Gene (19)OMIM (600046)HGNC:29GenCCUniProt (O95477)AlphaFoldClinVar (ABCA1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~147.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypoalphalipoproteinemia, primary, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011393

Submitter: PanelApp Australia

hypoalphalipoproteinemia, primary, 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011393

Submitter: Ambry Genetics

hypoalphalipoproteinemia, primary, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011393

Submitter: Labcorp Genetics (formerly Invitae)

Tangier diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008783

Submitter: Labcorp Genetics (formerly Invitae)

Tangier diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008783

Submitter: Orphanet

Tangier diseaseDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008783

Submitter: G2P

Tangier diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008783

Submitter: PanelApp Australia

apolipoprotein A-I deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100189

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hypoalphalipoproteinemia, primary, 1; Tangier diseaseAD/AR

Manifestation: Cardiovascular; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: Early cardiovascular events are common (eg, myocardial infarctions due to atherosclerosis), and while specific medical therapy is not currently available, preventive measures to decrease additional contributory atherosclerotic risk factors, as well as surveillance to allow early diagnosis and treatment of cardiovascular manifestations, may be beneficial

Refs: 14162531; 5831900; 4165386; 4165172; 198431; 190272; 194920; 195100; 75948; 7406376; 4082916; 3677505; 3799433; 3314502; 8432861; 7627690; 10431237; 10431236; 10525055; 9888879; 10533863; 16343506; 10535983; 10431238; 11086027; 11476965; 12084722; 12111371; 12111381; 12702168; 14742612; 16343506; 18955690; 19723515; 22179783; 22913675; 23430904Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCA1 variants in ClinVar

17 Conditions Cataloged
Cardiovascular phenotypeTotal: 948
not providedTotal: 913
not specifiedTotal: 189
Tangier diseaseTotal: 170
Hypoalphalipoproteinemia, primary, 1Total: 157
ABCA1-related disorderTotal: 28
Hypercholesterolemia, familial, 1Total: 3
Hypertrophic cardiomyopathyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005502.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
550
clinvar
9
clinvar
 567
missense
7
clinvar
12
clinvar
613
clinvar
136
clinvar
7
clinvar
 775
nonsense
16
clinvar
6
clinvar
2
clinvar
 24
start loss
0
frameshift
19
clinvar
2
clinvar
2
clinvar
 23
splice donor/acceptor (+/-2bp)
5
clinvar
11
clinvar
10
clinvar
 26
Total4731635686161415

Highest pathogenic variant AF is 0.00074051996

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005502.4RefSeqNP_005493.249MANE Select
ENST00000374736.8EnsemblENSP00000363868.349MANE Select
ENST00000374733.1EnsemblENSP00000363865.13Standard
ENST00000423487.6EnsemblENSP00000416623.27Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Fat digestion and absorption - Homo sapiens (human)
  • ABC transporters - Homo sapiens (human)
  • Cholesterol metabolism - Homo sapiens (human)
  • Selenium Micronutrient Network
  • Vitamin B12 Metabolism

Biological Process

  • protein lipidation
  • lipid transport
  • phagocytosis, engulfment
  • lysosome organization
  • G protein-coupled receptor signaling pathway

Molecular Function

  • signaling receptor binding
  • lipid transporter activity
  • protein binding
  • ATP binding
  • phospholipid binding

Cellular Component

  • endoplasmic reticulum membrane
  • Golgi apparatus
  • plasma membrane
  • integral component of plasma membrane
  • external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000374736
Coding exons
49
Length
147236
Individuals with no LoFs
125646
Homozygous LoFs
0
Heterozygous LoFs
102
Defined
125748
p
0.000406
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.7510291.20e+30.8570.000068414892
Missense (PolyPhen)262402.520.65094935
Synonymous-1.395074691.080.00002754399
Loss of Function6.23441170.3780.000006321357

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish0.000990.00099rare
East Asian0.000270.00027rare
Finnish0.000180.00018rare
European (Non-Finnish)0.000500.00050rare
South Asian0.000360.00036rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport.;
Disease
DISEASE: High density lipoprotein deficiency 1 (HDLD1) [MIM:205400]: Recessive disorder characterized by absence of high density lipoprotein (HDL) cholesterol from plasma, accumulation of cholesteryl esters, premature coronary artery disease (CAD), hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. {ECO:0000269|PubMed:10431236, ECO:0000269|PubMed:10431237, ECO:0000269|PubMed:10706591, ECO:0000269|PubMed:10938021, ECO:0000269|PubMed:11086027, ECO:0000269|PubMed:11257260, ECO:0000269|PubMed:11476961, ECO:0000269|PubMed:11476965, ECO:0000269|PubMed:11785958, ECO:0000269|PubMed:12111371, ECO:0000269|PubMed:12111381, ECO:0000269|PubMed:12407001, ECO:0000269|PubMed:14576201, ECO:0000269|PubMed:15019541, ECO:0000269|PubMed:15158913, ECO:0000269|PubMed:15262183, ECO:0000269|PubMed:15297675, ECO:0000269|PubMed:15520867}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: High density lipoprotein deficiency 2 (HDLD2) [MIM:604091]: Inherited as autosomal dominant trait. It is characterized by moderately low HDL cholesterol, predilection toward premature coronary artery disease (CAD) and a reduction in cellular cholesterol efflux. {ECO:0000269|PubMed:10431236, ECO:0000269|PubMed:10533863, ECO:0000269|PubMed:11086027, ECO:0000269|PubMed:12009425, ECO:0000269|PubMed:12204794, ECO:0000269|PubMed:15722566}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.676

Intolerance Scores

LoFtool
0.0388
RVIS EVS
-0.24
RVIS percentile EVS
36.29

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.694

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerHighMediumHigh
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