ABCA1

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

Basic information

Region (hg38): 9:104781005-104928155

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

Links

ENSG00000165029 ∙ NCBI:19 ∙ OMIM:600046 ∙ HGNC:29 ∙ Uniprot:O95477 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypoalphalipoproteinemia, primary, 1; Tangier disease	AD/AR	Cardiovascular	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	Cardiovascular; Neurologic; Ophthalmologic	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; 23430904

ClinVar

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

• not provided (773 variants)
• Cardiovascular phenotype (390 variants)
• Tangier disease (259 variants)
• Hypoalphalipoproteinemia, primary, 1 (246 variants)
• not specified (127 variants)
• Inborn genetic diseases (38 variants)
• Familial High Density Lipoprotein Deficiency (14 variants)
• Tangier disease;Hypoalphalipoproteinemia, primary, 1 (12 variants)
• Hypoalphalipoproteinemia, primary, 1;Tangier disease (12 variants)
• ABCA1-Related Disorders (3 variants)
• Hypercholesterolemia, familial, 1 (2 variants)
• ABCA1-related condition (1 variants)
• ABCA1-related dyslipidemia (1 variants)
• Symphalangism affecting the proximal phalanx of the 4th finger (1 variants)
• Early-onset coronary artery disease (1 variants)
• Breast carcinoma (1 variants)
• Familial hypoalphalipoproteinemia (1 variants)
• Familial hypercholesterolemia (1 variants)
• Reduced delayed hypersensitivity (1 variants)
• RECLASSIFIED - ABCA1 POLYMORPHISM (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	304	13	320
missense	3	2	316	45	14	380
nonsense	4	4				8
start loss						0
frameshift	6		1			7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	4	1			7
splice region		1	20	29	8	58
non coding			72	119	153	344
Total	15	10	395	468	180

Highest pathogenic variant AF is 0.0000402

Variants in ABCA1

This is a list of pathogenic ClinVar variants found in the ABCA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-104781036-T-A		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 12, 2018)
9-104781061-A-G		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Benign/Likely benign (Jan 13, 2018)
9-104781064-A-G		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Benign/Likely benign (Jan 13, 2018)
9-104781095-T-C		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Benign (May 10, 2021)
9-104781107-A-T		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Uncertain significance (Jan 13, 2018)
9-104781107-ATTT-A		Familial High Density Lipoprotein Deficiency • Tangier disease	Likely benign (Jun 14, 2016)
9-104781128-T-C		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781228-G-A		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
9-104781232-A-G		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Benign (Jan 13, 2018)
9-104781286-T-C		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781327-G-A		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Mar 16, 2018)
9-104781408-T-G		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Conflicting classifications of pathogenicity (Jan 12, 2018)
9-104781415-TAAC-T			Benign (May 08, 2021)
9-104781422-G-T		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Uncertain significance (Jan 13, 2018)
9-104781569-A-G		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781578-A-G		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Uncertain significance (Jan 13, 2018)
9-104781610-C-T		Tangier disease • Hypoalphalipoproteinemia, primary, 1	Benign (Jan 12, 2018)
9-104781662-G-C		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781670-C-T		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 15, 2018)
9-104781704-T-C		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Conflicting classifications of pathogenicity (Jan 12, 2018)
9-104781778-C-T		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781799-A-G		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781813-A-C		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 13, 2018)
9-104781829-A-G		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Conflicting classifications of pathogenicity (Jan 13, 2018)
9-104781869-T-G		Hypoalphalipoproteinemia, primary, 1 • Tangier disease	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCA1	protein_coding	protein_coding	ENST00000374736	49	147236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.45e-13	1.00	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.75	1029	1.20e+3	0.857	0.0000684	14892
Missense in Polyphen		262	402.52	0.6509		4935
Synonymous	-1.39	507	469	1.08	0.0000275	4399
Loss of Function	6.23	44	117	0.378	0.00000632	1357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000597	0.000597
Ashkenazi Jewish	0.000992	0.000993
East Asian	0.000272	0.000272
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000502	0.000501
Middle Eastern	0.000272	0.000272
South Asian	0.000359	0.000359
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

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