ABCA1

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

Basic information

Region (hg38): 9:104781006-104928155

Previous symbols: [ "ABC1", "HDLDT1" ]

Links

ENSG00000165029NCBI:19OMIM:600046HGNC:29Uniprot:O95477AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • apolipoprotein A-I deficiency (Supportive), mode of inheritance: AD
  • Tangier disease (Supportive), mode of inheritance: AR
  • hypoalphalipoproteinemia, primary, 1 (Limited), mode of inheritance: AD
  • Tangier disease (Strong), mode of inheritance: AR
  • hypoalphalipoproteinemia, primary, 1 (Definitive), mode of inheritance: AD
  • Tangier disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypoalphalipoproteinemia, primary, 1; Tangier diseaseAD/ARCardiovascularEarly 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 beneficialCardiovascular; Neurologic; Ophthalmologic14162531; 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; 23430904

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCA1 gene.

  • not_provided (813 variants)
  • Cardiovascular_phenotype (807 variants)
  • Tangier_disease (164 variants)
  • Hypoalphalipoproteinemia,_primary,_1 (157 variants)
  • not_specified (155 variants)
  • ABCA1-related_disorder (27 variants)
  • Hypertrophic_cardiomyopathy (2 variants)
  • Hypercholesterolemia,_familial,_1 (2 variants)
  • High_myopia (1 variants)
  • Symphalangism_affecting_the_proximal_phalanx_of_the_4th_finger (1 variants)
  • Decreased_HDL_cholesterol_concentration (1 variants)
  • Neurofibromatosis,_type_1 (1 variants)
  • Reduced_delayed_hypersensitivity (1 variants)
  • Tangier_disease,_variant (1 variants)
  • Familial_High_Density_Lipoprotein_Deficiency (1 variants)
  • ABCA1-related_dyslipidemia (1 variants)
  • Breast_carcinoma (1 variants)
  • Familial_hypercholesterolemia (1 variants)
  • Early-onset_coronary_artery_disease (1 variants)
  • Familial_hypoalphalipoproteinemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005502.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
497
clinvar
8
clinvar
508
missense
10
clinvar
10
clinvar
519
clinvar
110
clinvar
9
clinvar
658
nonsense
11
clinvar
5
clinvar
16
start loss
0
frameshift
16
clinvar
1
clinvar
1
clinvar
18
splice donor/acceptor (+/-2bp)
5
clinvar
11
clinvar
1
clinvar
17
Total 42 27 524 607 17

Highest pathogenic variant AF is 0.00074052

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ABCA1protein_codingprotein_codingENST00000374736 49147236
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.45e-131.0012564601021257480.000406
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.7510291.20e+30.8570.000068414892
Missense in Polyphen262402.520.65094935
Synonymous-1.395074691.080.00002754399
Loss of Function6.23441170.3780.000006321357

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005970.000597
Ashkenazi Jewish0.0009920.000993
East Asian0.0002720.000272
Finnish0.0001850.000185
European (Non-Finnish)0.0005020.000501
Middle Eastern0.0002720.000272
South Asian0.0003590.000359
Other0.000.00

dbNSFP

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.;
Pathway
Fat digestion and absorption - Homo sapiens (human);ABC transporters - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;SREBF and miR33 in cholesterol and lipid homeostasis;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Nuclear Receptors in Lipid Metabolism and Toxicity;Statin Pathway;HDL assembly;Plasma lipoprotein assembly;Transport of small molecules;Bile acid biosynthesis;Plasma lipoprotein assembly, remodeling, and clearance;RXR and RAR heterodimerization with other nuclear receptor (Consensus)

Recessive Scores

pRec
0.676

Intolerance Scores

loftool
0.0388
rvis_EVS
-0.24
rvis_percentile_EVS
36.29

Haploinsufficiency Scores

pHI
0.659
hipred
Y
hipred_score
0.706
ghis
0.460

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.694

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerHighMediumHigh

Mouse Genome Informatics

Gene name
Abca1
Phenotype
digestive/alimentary 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); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; liver/biliary system phenotype; respiratory 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); hematopoietic system phenotype; reproductive 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); pigmentation phenotype; endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype;

Gene ontology

Biological process
protein lipidation;lipid transport;phagocytosis, engulfment;lysosome organization;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;response to nutrient;cholesterol metabolic process;negative regulation of macrophage derived foam cell differentiation;positive regulation of cholesterol efflux;negative regulation of cholesterol storage;endosomal transport;regulation of lipid metabolic process;intracellular cholesterol transport;regulation of Cdc42 protein signal transduction;cholesterol efflux;phospholipid efflux;high-density lipoprotein particle assembly;response to laminar fluid shear stress;apolipoprotein A-I-mediated signaling pathway;response to drug;cholesterol homeostasis;reverse cholesterol transport;phospholipid translocation;interleukin-1 beta secretion;phospholipid homeostasis;platelet dense granule organization;cellular response to lipopolysaccharide;cellular response to retinoic acid;cellular response to cholesterol;cellular response to low-density lipoprotein particle stimulus;regulation of high-density lipoprotein particle assembly;anion transmembrane transport
Cellular component
endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of plasma membrane;external side of plasma membrane;endocytic vesicle;intracellular membrane-bounded organelle;membrane raft;phagocytic vesicle;perinuclear region of cytoplasm
Molecular function
signaling receptor binding;lipid transporter activity;protein binding;ATP binding;phospholipid binding;phospholipid transporter activity;high-density lipoprotein particle binding;anion transmembrane transporter activity;cholesterol binding;ATPase activity;cholesterol transporter activity;syntaxin binding;small GTPase binding;apolipoprotein binding;apolipoprotein A-I binding;apolipoprotein A-I receptor activity;ATPase activity, coupled to transmembrane movement of substances;ATPase binding;phosphatidylcholine-translocating ATPase activity;phosphatidylserine-translocating ATPase activity