ABCA1
Basic information
Region (hg38): 9:104781006-104928155
Previous symbols: [ "ABC1", "HDLDT1" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 497 | 508 | ||||
missense | 10 | 10 | 519 | 110 | 658 | |
nonsense | 11 | 16 | ||||
start loss | 0 | |||||
frameshift | 16 | 18 | ||||
splice donor/acceptor (+/-2bp) | 11 | 17 | ||||
Total | 42 | 27 | 524 | 607 | 17 |
Highest pathogenic variant AF is 0.00074052
GnomAD
Source:
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:
- 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