ABCA1

Summary

ABCA1 (ATP binding cassette subfamily A member 1, HGNC:29) is a protein-coding gene on chromosome 9q31.1, encoding Phospholipid-transporting ATPase ABCA1 (O95477). Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.

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.

Source: NCBI Gene 19 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypoalphalipoproteinemia, primary, 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 210
• Clinical variants (ClinVar): 1,936 total — 63 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes
• MANE Select transcript: NM_005502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29
Approved symbol	ABCA1
Name	ATP binding cassette subfamily A member 1
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	TGD
Ensembl gene	ENSG00000165029
Ensembl biotype	protein_coding
OMIM	600046
Entrez	19

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374733, ENST00000374736, ENST00000423487, ENST00000494467, ENST00000678995

RefSeq mRNA: 1 — MANE Select: NM_005502 NM_005502

CCDS: CCDS6762

Canonical transcript exons

ENST00000374736 — 50 exons

Exon	Start	End
ENSE00001089456	104785396	104785639
ENSE00001089457	104814427	104814475
ENSE00001089458	104832574	104832771
ENSE00001089461	104796053	104796197
ENSE00001089463	104816143	104816345
ENSE00001089467	104804626	104804720
ENSE00001089468	104812574	104812722
ENSE00001089469	104809466	104809564
ENSE00001089471	104810800	104810924
ENSE00001089472	104790922	104791028
ENSE00001089473	104792786	104792906
ENSE00001089474	104824465	104824578
ENSE00001089478	104837428	104837567
ENSE00001089479	104786873	104786976
ENSE00001089480	104794387	104794510
ENSE00001089482	104830925	104831101
ENSE00001089484	104814118	104814231
ENSE00001089485	104831622	104831827
ENSE00001089486	104788426	104788567
ENSE00001089487	104803284	104803316
ENSE00001089488	104791936	104791998
ENSE00001089491	104798421	104798598
ENSE00001089492	104817332	104817404
ENSE00001089493	104821375	104821506
ENSE00001089494	104796309	104796424
ENSE00001089496	104825683	104825887
ENSE00001089497	104806241	104806430
ENSE00001089500	104802054	104802159
ENSE00001089502	104822496	104822667
ENSE00001089505	104793171	104793300
ENSE00001089512	104799819	104799988
ENSE00001089514	104883039	104883157
ENSE00001089515	104845477	104845569
ENSE00001089517	104787920	104788054
ENSE00001089518	104819586	104819723
ENSE00001089520	104818663	104818883
ENSE00001089523	104836980	104837096
ENSE00001089525	104786298	104786390
ENSE00001137741	104800510	104800584
ENSE00001137821	104819927	104820069
ENSE00001137893	104840279	104840519
ENSE00001143998	104781006	104784455
ENSE00001651460	104858522	104858698
ENSE00001810407	104927935	104928155
ENSE00002178768	104861679	104861800
ENSE00002201214	104903614	104903771
ENSE00003480600	104826948	104827169
ENSE00003502099	104828916	104829138
ENSE00003559924	104884427	104884568
ENSE00003593541	104889102	104889195

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.9441 / max 554.5432, expressed in 1564 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101805	36.8509	1563
101794	0.0475	15
101795	0.0458	15

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	94.92	gold quality
skin of hip	UBERON:0001554	92.94	gold quality
left adrenal gland	UBERON:0001234	92.68	gold quality
adrenal gland	UBERON:0002369	92.45	gold quality
left adrenal gland cortex	UBERON:0035825	91.99	gold quality
right adrenal gland	UBERON:0001233	91.80	gold quality
adrenal cortex	UBERON:0001235	91.78	gold quality
upper leg skin	UBERON:0004262	91.53	gold quality
right adrenal gland cortex	UBERON:0035827	91.44	gold quality
colonic epithelium	UBERON:0000397	90.99	gold quality
stromal cell of endometrium	CL:0002255	90.59	gold quality
lower lobe of lung	UBERON:0008949	90.45	gold quality
liver	UBERON:0002107	90.26	gold quality
decidua	UBERON:0002450	90.22	gold quality
corpus epididymis	UBERON:0004359	89.76	gold quality
tibialis anterior	UBERON:0001385	89.26	gold quality
placenta	UBERON:0001987	89.18	gold quality
cauda epididymis	UBERON:0004360	88.71	gold quality
urinary bladder	UBERON:0001255	88.55	gold quality
adipose tissue	UBERON:0001013	88.13	gold quality
right lobe of liver	UBERON:0001114	87.90	gold quality
connective tissue	UBERON:0002384	87.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.95	gold quality
caput epididymis	UBERON:0004358	86.79	gold quality
pigmented layer of retina	UBERON:0001782	86.64	gold quality
calcaneal tendon	UBERON:0003701	86.28	gold quality
right coronary artery	UBERON:0001625	86.12	gold quality
gall bladder	UBERON:0002110	85.86	gold quality
superficial temporal artery	UBERON:0001614	85.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.55	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	1283.76
E-MTAB-8142	yes	55.10
E-GEOD-93593	yes	6.19
E-MTAB-7249	yes	2.75
E-CURD-11	no	1039.40
E-GEOD-124858	no	664.85
E-GEOD-99795	no	45.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ARNT, CELF1, CREB1, DNMT1, E2F1, FOSL2, FOXA1, FOXA2, GLI2, GTF3A, HIF1A, HNF1A, HNF4A, NCOA1, NCOR1, NCOR2, NFATC2, NFKB1, NFKB, NFKBID, NR0B2, NR1H2, NR1H3, NR1H4, NR1I2, NR3C1, PPARA, PPARG, PREB, RARA, RARG, RELA, RXRA, SMARCA2, SMARCA4, SP1, SP3, SREBF2, STAT1

miRNA regulators (miRDB)

215 targeting ABCA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 40)

• su(f) is required for the cleavage of pre-mRNA during mRNA 3’ end formation (PMID:12149458)
• function as a regulator rather than an active transporter (PMID:11700048)
• in the presence of apoE, overexpression of ABCA1 modulates HDL as well as apoB-containing lipoprotein metabolism and reduces atherosclerosis in vivo (PMID:11752403)
• contributes to the secretion of interleukin 1beta from macrophages (PMID:11855831)
• a novel site in the human ABCA1 promoter involved in the regulation of ABCA1 gene expression. (PMID:11861672)
• Role as a phosphatidylserine translocase (PMID:11893753)
• Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux (PMID:11929608)
• ABCA1 regulatory variants influence coronary artery disease independent of effects on plasma lipid levels (PMID:11940086)
• Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation. (PMID:11950847)
• ABCA1 mutations can disrupt its direct interaction with apolipoprotein A-I. (PMID:12084722)
• Increased ABCA1 activity protects against atherosclerosis. ABCA1(human transgenic)(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. (PMID:12093886)
• R1680W mutation associated with Tangier disease, phenotypes variable. (PMID:12111371)
• REVIEW: ATP-binding cassette transporter A1 and cholesterol trafficking (PMID:12151852)
• Dominant expression of ABCA1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands (PMID:12176027)
• A novel serine (Ser-2054) on the ABCA1 protein crucial for PKA phosphorylation and for regulation of ABCA1 transporter activity. (PMID:12196520)
• Recent data confirms that a single defective allele in ABCA1 may be assosiated with reduced HDL cholesterol and FHA. (PMID:12204794)
• The association of FADD with ABCA1 provides an unexpected link between high density lipoprotein metabolism and an adaptor molecule mainly described in death receptor signal transduction. (PMID:12235128)
• findings suggest an important role for hepatocyte basolateral membrane ABCA1 in the regulation of the levels of intracellular hepatic cholesterol, as well as plasma HDL (PMID:12359250)
• ABCA1 plays an important role in artery wall cell-mediated modification/oxidation of LDL by modulating the release of reactive oxygen species from artery wall cells that are necessary for LDL oxidation. (PMID:12426219)
• ABCA1 is regulated by PEST sequence-mediated calpain proteolysis that appears to be reversed by apolipoprotein-mediated phospholipid efflux (PMID:12511593)
• Golgi is involved in ABCA1-mediated cholesterol efflux. (PMID:12551894)
• examine the necessary structural features for a protein to promote lipid efflux by the ABCA1 transporter and find the amphipathic helix is a key structural motif for peptide-mediated lipid efflux from ABCA1, but there is no stereoselective requirement (PMID:12562845)
• Results describe two new point mutations of the ABCA1 gene found in one patient with Tangier disease and the sibling of another Tangier disease patient. (PMID:12576507)
• Genetic variability of ABCA1 influences development of Alzheimer’s disease,possibly by interfering with CNS cholesterol homeostasis. (PMID:12600718)
• Review. Transgenic mice with human ABCA1 genes are used to study its function in cholesterol transport, apo B lipoproteins, and atherosclerosis. (PMID:12615681)
• The K allele was significantly more frequent in FH subjects without premature CHD than in FH subjects with premature CHD suggesting that the genetic variant R219K in ABCA1 could influence the development and progression of atherosclerosis in FH subjects. (PMID:12624133)
• ABCA1 expression varies among tissues, and cholesterol conversion to hydroxycholesterol is an important mechanism for the maintenance of cholesterol homeostasis in fibroblasts (PMID:12706378)
• While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with coronary artery disease status in Malays with no effects on HDL-C or apoA1. (PMID:12709788)
• hepatic overexpression of ABCA1 showed a selective increase in HDL cholesterol (PMID:12730295)
• In this study we review how genetic variation at the ABCA1 locus affects its role in the maintenance of lipid homeostasis and the natural progression of atherosclerosis. (PMID:12763760)
• regulation of ABCA1 mRNA levels exploits the use of alternative transcription start sites (PMID:12804586)
• ABCA1 has a role in the low levels of HDL-cholesterol and overaccumulation of cellular lipids in Niemann-Pick Disease type C (PMID:12813037)
• Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. (PMID:12869555)
• results indicate that the K219 allele frequency of adenosine triphosphate binding cassette transporter 1 differs markedly between blacks and whites (PMID:12870173)
• ABCA1-mediated vesicle release involves lipid raft plasma membrane domains (PMID:12928428)
• ABCA1 is phosphorylated and stabilized in a pathway in which apoA-I activates PKC alpha by PC-PLC-mediated generation of diacylglycerol (PMID:12952980)
• These studies indicate a direct role of retinoic acid receptor gamma/retinoid x receptor in induction of macrophage ABCA1. (PMID:14560020)
• ABCA7 compensates the function of ABCA1 for release of cell cholesterol in a certain condition(s). (PMID:14570867)
• ABCA1 gene sequence in a proband with very low HDL cholesterol and premature coronary heart disease family history revealed 2 mutations: G5947A (R1851Q) and single thymidine deletion in a polypyrimidine tract 33 to 46 bps upstream from start of exon 47 (PMID:14576201)
• Of special interest was our finding that the effects of compromised ABCA1 function on HDL were more pronounced in women than in men. (PMID:14644402)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	abca1a	ENSDARG00000074635
mus_musculus	Abca1	ENSMUSG00000015243
rattus_norvegicus	Abca1	ENSRNOG00000018126
drosophila_melanogaster	Eato	FBGN0028539
drosophila_melanogaster	CG8908	FBGN0034493
caenorhabditis_elegans		WBGENE00000019
caenorhabditis_elegans	abt-2	WBGENE00000020
caenorhabditis_elegans	abt-5	WBGENE00000023

Paralogs (11): ABCA7 (ENSG00000064687), ABCA2 (ENSG00000107331), ABCA8 (ENSG00000141338), ABCA12 (ENSG00000144452), ABCA9 (ENSG00000154258), ABCA6 (ENSG00000154262), ABCA10 (ENSG00000154263), ABCA5 (ENSG00000154265), ABCA3 (ENSG00000167972), ABCA13 (ENSG00000179869), ABCA4 (ENSG00000198691)

Protein

Protein identifiers

Phospholipid-transporting ATPase ABCA1 — O95477 (reviewed: O95477)

Alternative names: ATP-binding cassette sub-family A member 1, ATP-binding cassette transporter 1, Cholesterol efflux regulatory protein

All UniProt accessions (4): A0A7I2V5U0, B1AMI1, B1AMI2, O95477

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs. Transports preferentially phosphatidylcholine over phosphatidylserine. May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs. Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain.

Subunit / interactions. Interacts with MEGF10. May interact with APOE1; functionally associated with APOE1 in the biogenesis of HDLs. Interacts with ABCA8; this interaction potentiates cholesterol efflux. Interacts with ABCA12 and NR1H2; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability.

Subcellular location. Cell membrane. Endosome.

Tissue specificity. Widely expressed, but most abundant in macrophages.

Post-translational modifications. Phosphorylation on Ser-2054 regulates phospholipid efflux. Palmitoylated by ZDHHC8. Palmitoylation is essential for localization to the plasma membrane.

Disease relevance. Tangier disease (TGD) [MIM:205400] An autosomal recessive disorder characterized by near absence of plasma high density lipoproteins, low serum HDL cholesterol, and massive tissue deposition of cholesterol esters. Clinical features include large yellow-orange tonsils, hepatomegaly, splenomegaly, enlarged lymph nodes, and often sensory polyneuropathy. The disease is caused by variants affecting the gene represented in this entry. Hypoalphalipoproteinemia, primary, 1 (FHA1) [MIM:604091] An autosomal dominant disorder characterized by decreased plasma high density lipoproteins, moderately low HDL cholesterol, a reduction in cellular cholesterol efflux, and susceptibility to premature coronary artery disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylcholine and to a lesser degree by phosphatidylserine and sphingomyelin. Phospholipid translocase activity is highly reduced by berylium fluoride and aluminum flouride and reduced by N-ethylmaleimide.

Domain organisation. Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.

Induction. By bacterial lipopolysaccharides (LPS). LPS regulates expression through a liver X receptor (LXR) -independent mechanism. Repressed by ZNF202.

Polymorphism. Genetic variations in ABCA1 define the high density lipoprotein cholesterol level quantitative trait locus 13 (HDLCQ13) [MIM:600046].

Similarity. Belongs to the ABC transporter superfamily. ABCA family.

RefSeq proteins (1): NP_005493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR013525	ABC2_TM	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR026082	ABCA	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR056264	R2_ABCA1-4-like	Domain

Pfam: PF00005, PF12698, PF23321

Catalyzed reactions (Rhea), 4 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + phosphate + H(+) (RHEA:38567)
• a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + phosphate + H(+) (RHEA:38583)
• a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+) (RHEA:38903)
• cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+) (RHEA:39051)

UniProt features (325 total): helix 84, sequence variant 73, strand 66, mutagenesis site 23, glycosylation site 21, turn 18, transmembrane region 15, sequence conflict 4, region of interest 4, lipid moiety-binding region 4, modified residue 3, topological domain 2, domain 2, binding site 2, disulfide bond 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7TBW	ELECTRON MICROSCOPY	3.1
7TC0	ELECTRON MICROSCOPY	3.1
7TBY	ELECTRON MICROSCOPY	4
7TDT	ELECTRON MICROSCOPY	4
5XJY	ELECTRON MICROSCOPY	4.1
7ROQ	ELECTRON MICROSCOPY	4.1
7TBZ	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95477-F1	73.50	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 933–940; 1946–1953

Post-translational modifications (7): 1042, 1296, 2054, 3, 23, 1110, 1111

Disulfide bonds (2): 75–309, 1463–1477

Glycosylation sites (21): 14, 98, 151, 161, 196, 244, 292, 337, 349, 400, 478, 489, 521, 820, 1144, 1294, 1453, 1504, 1637, 2044 …

Mutagenesis-validated functional residues (23):

Position	Phenotype
3	mild decrease of palmitoylation. loss of localization to plasma membrane. decreased cholesterol efflux. decreased phosph
23	mild decrease of palmitoylation. loss of localization to plasma membrane. decreased palmitoylation; when associated with
74	85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
100	highly decreased protein abundance. highly decreased atpase activity. highly decreased phospholipid translocase activity
304	no effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with c-308.
308	no effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with c-304.
371	no effect on phospholipid and cholesterol efflux or localization to cell membrane. 85-90% reduction in phospholipid and
371	85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
375	85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
568	60-65% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane.
573	no effect on phospholipid and cholesterol efflux and on localization to cell membrane.
581	80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
583	90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
584	80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
585	80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
590	90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated
593	moderately decreased protein abundance. highly decreased atpase activity. highly decreased phospholipid translocase acti
939	inhibits atpase activity; when associated with m-1952. decreases translocase activity; when associated with m-1952. does
1110	decreased palmitoylation; when associated with s-3, s-23 and s-1111.
1111	decreased palmitoylation; when associated with s-3, s-23 and s-1110.
1512	moderately decreased protein abundance. does not affect atpase activity. moderately decreased phospholipid translocase a
1952	inhibits atpase activity; when associated with m-939. decreases translocase activity; when associated with m-939. does n

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-5682113	Defective ABCA1 causes TGD
R-HSA-8963896	HDL assembly
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling

MSigDB gene sets: 677 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_VACUOLE_ORGANIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_VESICLE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, TTTGTAG_MIR520D, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, MODULE_45

GO Biological Process (48): peptide secretion (GO:0002790), phagocytosis, engulfment (GO:0006911), lysosome organization (GO:0007040), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cholesterol metabolic process (GO:0008203), protein secretion (GO:0009306), negative regulation of macrophage derived foam cell differentiation (GO:0010745), positive regulation of cholesterol efflux (GO:0010875), negative regulation of cholesterol storage (GO:0010887), endosomal transport (GO:0016197), signal release (GO:0023061), intracellular cholesterol transport (GO:0032367), regulation of Cdc42 protein signal transduction (GO:0032489), cholesterol efflux (GO:0033344), response to vitamin B3 (GO:0033552), phospholipid efflux (GO:0033700), high-density lipoprotein particle assembly (GO:0034380), response to laminar fluid shear stress (GO:0034616), lipoprotein biosynthetic process (GO:0042158), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), phospholipid translocation (GO:0045332), phospholipid homeostasis (GO:0055091), platelet dense granule organization (GO:0060155), cellular response to lipopolysaccharide (GO:0071222), cellular response to retinoic acid (GO:0071300), cellular response to cytokine stimulus (GO:0071345), cellular response to cholesterol (GO:0071397), cellular response to low-density lipoprotein particle stimulus (GO:0071404), cellular response to xenobiotic stimulus (GO:0071466), protein transmembrane transport (GO:0071806), regulation of high-density lipoprotein particle assembly (GO:0090107), positive regulation of high-density lipoprotein particle assembly (GO:0090108), export across plasma membrane (GO:0140115), lipid metabolic process (GO:0006629), response to nutrient (GO:0007584), steroid metabolic process (GO:0008202), response to xenobiotic stimulus (GO:0009410), organic hydroxy compound transport (GO:0015850)

GO Molecular Function (24): signaling receptor binding (GO:0005102), ATP binding (GO:0005524), obsolete phospholipid transporter activity (GO:0005548), high-density lipoprotein particle binding (GO:0008035), transmembrane protein transporter activity (GO:0008320), cholesterol binding (GO:0015485), ATP hydrolysis activity (GO:0016887), syntaxin binding (GO:0019905), phosphatidylcholine binding (GO:0031210), small GTPase binding (GO:0031267), apolipoprotein binding (GO:0034185), apolipoprotein A-I binding (GO:0034186), apolipoprotein A-I receptor activity (GO:0034188), ATPase-coupled transmembrane transporter activity (GO:0042626), sphingolipid floppase activity (GO:0046623), ATPase binding (GO:0051117), phosphatidylcholine floppase activity (GO:0090554), phosphatidylserine floppase activity (GO:0090556), cholesterol transfer activity (GO:0120020), floppase activity (GO:0140328), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATPase-coupled intramembrane lipid carrier activity (GO:0140326)

GO Cellular Component (13): endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), basolateral plasma membrane (GO:0016323), endocytic vesicle (GO:0030139), membrane raft (GO:0045121), phagocytic vesicle (GO:0045335), perinuclear region of cytoplasm (GO:0048471), intracellular vesicle (GO:0097708), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
ABC transporter disorders	1
Plasma lipoprotein assembly	1
NR1H2 and NR1H3-mediated signaling	1
Transport of small molecules	1
Metabolism of lipids	1
Metabolism	1
Disorders of transmembrane transporters	1
Disease	1
Plasma lipoprotein assembly, remodeling, and clearance	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
floppase activity	3
cellular anatomical structure	3
secretion by cell	2
intracellular anatomical structure	2
cholesterol transport	2
protein binding	2
ATP-dependent activity	2
endomembrane system	2
cytoplasmic vesicle	2
cytoplasm	2
intracellular membrane-bounded organelle	2
peptide transport	1
secretion	1
phagocytosis	1
plasma membrane invagination	1
lytic vacuole organization	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
sterol metabolic process	1
secondary alcohol metabolic process	1
protein transport	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
cholesterol storage	1
regulation of cholesterol storage	1
negative regulation of lipid storage	1
vesicle-mediated transport	1
intracellular transport	1
cell-cell signaling	1
intracellular sterol transport	1
Cdc42 protein signal transduction	1
regulation of Rho protein signal transduction	1

Protein interactions and networks

STRING

3322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA1	APOA1	P02647	999
ABCA1	APOE	P02649	979
ABCA1	SREBF2	Q12772	939
ABCA1	XPR1	Q9UBH6	939
ABCA1	NR1H3	Q13133	935
ABCA1	SCARB1	Q8WTV0	933
ABCA1	LCAT	P04180	911
ABCA1	SREBF1	P36956	904
ABCA1	NR1H2	P55055	900
ABCA1	APOA2	P02652	872
ABCA1	HMGCR	P04035	866
ABCA1	APOB	P04114	862
ABCA1	CYP7A1	P22680	857
ABCA1	CETP	P11597	830
ABCA1	GULP1	Q9UBP9	829

IntAct

179 interactions, top by confidence:

A	B	Type	Score
ABCA1	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.700
SNTB1	ABCA1	psi-mi:“MI:0915”(physical association)	0.700
ABCA1	SNTB1	psi-mi:“MI:0915”(physical association)	0.700
ABCA1	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.660
ABCA1	SNTA1	psi-mi:“MI:0915”(physical association)	0.660
APOA1	ABCA1	psi-mi:“MI:0403”(colocalization)	0.620
ABCA1	APOA1	psi-mi:“MI:0403”(colocalization)	0.620
ABCA1	APOA1	psi-mi:“MI:0915”(physical association)	0.620
APOA1	ABCA1	psi-mi:“MI:0915”(physical association)	0.620
ABCA1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.610
MPDZ	ABCA1	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	DLG3	psi-mi:“MI:0915”(physical association)	0.610
ARHGEF11	ABCA1	psi-mi:“MI:0915”(physical association)	0.610
MPDZ	ABCA1	psi-mi:“MI:0915”(physical association)	0.610
DLG2	ABCA1	psi-mi:“MI:0915”(physical association)	0.610
LIN7B	ABCA1	psi-mi:“MI:0915”(physical association)	0.610
ABCA1	ABCA12	psi-mi:“MI:0403”(colocalization)	0.590
ABCA12	ABCA1	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (50): ABCA1 (Affinity Capture-MS), ABCA1 (Affinity Capture-MS), NR1H2 (Affinity Capture-Western), NR1H2 (Affinity Capture-Western), FADD (Two-hybrid), ABCA1 (Affinity Capture-MS), APOA1 (Affinity Capture-Western), ABCA1 (Affinity Capture-Western), COPS2 (Affinity Capture-Western), ABCA1 (Affinity Capture-Western), Hectd1 (Affinity Capture-Western), ABCA1 (Reconstituted Complex), FADD (Reconstituted Complex), ABCA1 (Proximity Label-MS), ABCA1 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2K1Q8, B2RX12, E9PU17, E9PX95, F1MWM0, O00329, O15438, O35600, O75899, O88563, O88871, O94911, O95477, P41233, P55205, P58428, P78363, Q09427, Q09428, Q09429, Q2NKY8, Q5BJS0, Q5R607, Q5ZI74, Q6TL19, Q7L2E3, Q7TNJ2, Q80T41, Q84M24, Q8CF82, Q8IUA7, Q8K440, Q8K441, Q8K442, Q8K448, Q8K449, Q8LPK0, Q8N139, Q8NCL4, Q8R420

Diamond homologs: A0A0G2K1Q8, C0SPB4, E9PU17, E9PX95, E9Q876, F1MWM0, O35600, O52618, O95477, P08720, P0A9U1, P0A9U2, P0DXG8, P0DXU5, P0DXU7, P19844, P22040, P23703, P26050, P30750, P32010, P36879, P37624, P41233, P41234, P44785, P50332, P54592, P55476, P63355, P63356, P70970, P72335, P78363, P94374, P94440, Q05067, Q0I5E9, Q0TLD2, Q13ZJ1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
ABCA1	“up-regulates activity”	APOA1	binding
APOA1	“up-regulates quantity by stabilization”	ABCA1	binding
ABCA1	up-regulates	HDL_assembly
EGFR	“down-regulates quantity by destabilization”	ABCA1	phosphorylation
ABCA1	“up-regulates activity”	MEGF10	binding
MEGF10	“up-regulates activity”	ABCA1	binding
PRKACA	“up-regulates activity”	ABCA1	phosphorylation
LNX1	“down-regulates quantity by destabilization”	ABCA1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	40.8×	9e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	38.8×	9e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.8×	9e-06
Long-term potentiation	5	34.0×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	32.6×	1e-09
Neurexins and neuroligins	10	28.1×	6e-10
Formation of the dystrophin-glycoprotein complex (DGC)	6	26.5×	9e-06
Protein-protein interactions at synapses	6	22.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	63.3×	5e-15
protein localization to synapse	6	45.5×	7e-07
receptor clustering	6	37.1×	2e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	34.4×	4e-07
establishment of cell polarity	5	19.0×	4e-04
protein-containing complex assembly	9	10.2×	2e-05
cell-cell adhesion	10	10.1×	8e-06
protein localization to plasma membrane	7	7.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1936 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	28
Uncertain significance	665
Likely benign	733
Benign	192

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1360777	NM_005502.4(ABCA1):c.975del (p.Trp324_Tyr325insTer)	Pathogenic
1443024	NM_005502.4(ABCA1):c.4347_4348del (p.Phe1449fs)	Pathogenic
144971	GRCh38/hg38 9q22.32-31.3(chr9:95061030-108695569)x1	Pathogenic
1456561	NM_005502.4(ABCA1):c.16C>T (p.Gln6Ter)	Pathogenic
1457817	NM_005502.4(ABCA1):c.101_104del (p.Phe34fs)	Pathogenic
147624	GRCh38/hg38 9q21.11-31.2(chr9:68420430-106579493)x3	Pathogenic
149828	GRCh38/hg38 9p24.3-q34.3(chr9:193412-138124524)x3	Pathogenic
1527491	GRCh37/hg19 9p24.3-q34.3(chr9:353349-141020389)	Pathogenic
155409	GRCh38/hg38 9p24.3-q34.3(chr9:203862-138125937)x3	Pathogenic
161058	GRCh38/hg38 9q22.33-33.1(chr9:99138048-115011033)x1	Pathogenic
1929414	NM_005502.4(ABCA1):c.1775del (p.Gly592fs)	Pathogenic
2087161	NM_005502.4(ABCA1):c.2855del (p.Pro952fs)	Pathogenic
253402	GRCh37/hg19 9p24.3-q34.3(chr9:163131-141122114)x3	Pathogenic
2579281	GRCh38/hg38 9q31.1-31.3(chr9:102995214-108903040)x1	Pathogenic
2627928	NM_005502.4(ABCA1):c.5636+1G>A	Pathogenic
2671591	Single allele	Pathogenic
2735310	NM_005502.4(ABCA1):c.5551C>T (p.Arg1851Ter)	Pathogenic
2735311	NM_005502.4(ABCA1):c.5520del (p.Phe1840fs)	Pathogenic
2735314	NM_005502.4(ABCA1):c.1669C>T (p.Arg557Ter)	Pathogenic
2794859	NM_005502.4(ABCA1):c.4449del (p.Leu1484fs)	Pathogenic
2806056	NM_005502.4(ABCA1):c.1510-2A>C	Pathogenic
2847432	NM_005502.4(ABCA1):c.4864_4867dup (p.Asn1623fs)	Pathogenic
2862987	NM_005502.4(ABCA1):c.1680dup (p.Asp561Ter)	Pathogenic
32222	GRCh38/hg38 9q22.33-33.1(chr9:99138048-115011033)x1	Pathogenic
3224730	NM_005502.4(ABCA1):c.1768dup (p.Trp590fs)	Pathogenic
3256126	NM_005502.4(ABCA1):c.2302C>T (p.Gln768Ter)	Pathogenic
3339293	NM_005502.4(ABCA1):c.1979del (p.Val660fs)	Pathogenic
3393044	GRCh37/hg19 9q31.1-32(chr9:106443221-115687164)x1	Pathogenic
3573478	NM_005502.4(ABCA1):c.4465-1G>C	Pathogenic
3618082	NM_005502.4(ABCA1):c.1769G>A (p.Trp590Ter)	Pathogenic

SpliceAI

7540 predictions. Top by Δscore:

Variant	Effect	Δscore
9:104784456:C:T	acceptor_loss	1.0000
9:104784457:T:A	acceptor_loss	1.0000
9:104785392:TTA:T	donor_loss	1.0000
9:104785394:A:AC	donor_gain	1.0000
9:104785394:ACTTG:A	donor_loss	1.0000
9:104785395:C:CC	donor_gain	1.0000
9:104785395:CT:C	donor_gain	1.0000
9:104785395:CTT:C	donor_gain	1.0000
9:104785638:ACCTG:A	acceptor_loss	1.0000
9:104786300:A:AC	donor_gain	1.0000
9:104786391:C:CC	acceptor_gain	1.0000
9:104786896:T:C	donor_gain	1.0000
9:104786900:C:A	donor_gain	1.0000
9:104786903:T:TA	donor_gain	1.0000
9:104786918:AGGG:A	donor_gain	1.0000
9:104787912:ATACT:A	donor_loss	1.0000
9:104787915:CTCA:C	donor_loss	1.0000
9:104787916:TCA:T	donor_loss	1.0000
9:104787917:CAC:C	donor_loss	1.0000
9:104787918:A:AC	donor_gain	1.0000
9:104787919:C:CC	donor_gain	1.0000
9:104788050:CCAAC:C	acceptor_gain	1.0000
9:104788051:CAACC:C	acceptor_gain	1.0000
9:104788053:AC:A	acceptor_gain	1.0000
9:104788054:CC:C	acceptor_gain	1.0000
9:104788055:CTAC:C	acceptor_loss	1.0000
9:104788059:A:T	acceptor_gain	1.0000
9:104788423:TACC:T	donor_loss	1.0000
9:104788424:A:C	donor_loss	1.0000
9:104788436:T:TA	donor_gain	1.0000

AlphaMissense

14937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:104784450:A:C	F2217L	1.000
9:104784450:A:T	F2217L	1.000
9:104784452:A:G	F2217L	1.000
9:104785418:A:T	V2208D	1.000
9:104786307:A:G	L2131P	1.000
9:104786323:C:G	G2126R	1.000
9:104786334:A:G	F2122S	1.000
9:104786352:A:T	I2116N	1.000
9:104786356:C:G	A2115P	1.000
9:104786366:G:C	C2111W	1.000
9:104786367:C:T	C2111Y	1.000
9:104786368:A:G	C2111R	1.000
9:104786378:A:C	C2107W	1.000
9:104786380:A:G	C2107R	1.000
9:104786879:G:A	S2101F	1.000
9:104786879:G:T	S2101Y	1.000
9:104786885:A:G	L2099P	1.000
9:104786931:A:G	W2084R	1.000
9:104786931:A:T	W2084R	1.000
9:104786969:G:T	P2071H	1.000
9:104786972:T:A	E2070V	1.000
9:104786972:T:C	E2070G	1.000
9:104786972:T:G	E2070A	1.000
9:104786973:C:T	E2070K	1.000
9:104787921:A:G	L2068P	1.000
9:104787972:C:G	R2051P	1.000
9:104787973:G:T	R2051S	1.000
9:104788522:G:C	C1991W	1.000
9:104790994:T:A	K1952I	1.000
9:104791013:C:G	G1946R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003295 (9:104829439 A>C), RS1000009358 (9:104921651 T>C), RS1000016621 (9:104820124 G>C,T), RS1000031512 (9:104813954 G>C), RS1000036041 (9:104899238 C>T), RS1000040827 (9:104807199 T>C), RS1000074394 (9:104916380 C>T), RS1000103175 (9:104813627 G>A), RS1000113799 (9:104876499 T>G), RS1000135572 (9:104841473 C>G), RS1000153914 (9:104812313 C>A,T), RS1000163127 (9:104887817 C>T), RS1000193534 (9:104795679 A>G), RS1000202619 (9:104841157 C>T), RS1000207379 (9:104922031 G>T)

Disease associations

OMIM: gene MIM:600046 | disease phenotypes: MIM:604091, MIM:205400, MIM:143890, MIM:614846, MIM:162200, MIM:236670, MIM:618619

GenCC curated gene-disease

Disease	Classification	Inheritance
hypoalphalipoproteinemia, primary, 1	Definitive	Autosomal dominant
Tangier disease	Definitive	Autosomal recessive
apolipoprotein A-I deficiency	Supportive	Autosomal dominant

Mondo (12): hypoalphalipoproteinemia, primary, 1 (MONDO:0011393), Tangier disease (MONDO:0008783), hypertrophic cardiomyopathy (MONDO:0005045), breast carcinoma (MONDO:0004989), hypercholesterolemia, familial, 1 (MONDO:0007750), distal tetrasomy 15q (MONDO:0013918), neurofibromatosis type 1 (MONDO:0018975), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), Weiss-Kruszka syndrome (MONDO:0032836), hypoalphalipoproteinemia (MONDO:0017773), familial hypercholesterolemia (MONDO:0005439), (MONDO:0100189)

Orphanet (10): Apolipoprotein A-I deficiency (Orphanet:425), Tangier disease (Orphanet:31150), Rare hypertrophic cardiomyopathy (Orphanet:217569), Homozygous familial hypercholesterolemia (Orphanet:391665), 15q overgrowth syndrome (Orphanet:314585), Distal triplication 15q syndrome (Orphanet:314588), Neurofibromatosis type 1 (Orphanet:636), Walker-Warburg syndrome (Orphanet:899), Weiss-Kruszka Syndrome (Orphanet:502430), Hypoalphalipoproteinemia (Orphanet:31153)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000622	Blurred vision
HP:0000656	Ectropion
HP:0000958	Dry skin
HP:0000991	Xanthomatosis
HP:0001114	Xanthelasma
HP:0001265	Hyporeflexia
HP:0001349	Facial diplegia
HP:0001433	Hepatosplenomegaly
HP:0001658	Myocardial infarction
HP:0001677	Coronary artery atherosclerosis
HP:0001681	Angina pectoris
HP:0001712	Left ventricular hypertrophy
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0002027	Abdominal pain
HP:0002155	Hypertriglyceridemia
HP:0002164	Nail dysplasia
HP:0002240	Hepatomegaly
HP:0002460	Distal muscle weakness
HP:0002621	Atherosclerosis
HP:0002730	Chronic noninfectious lymphadenopathy
HP:0003119	Abnormal circulating lipid concentration
HP:0003146	Hypocholesterolemia
HP:0003233	Decreased HDL cholesterol concentration
HP:0003396	Syringomyelia
HP:0003477	Peripheral axonal neuropathy

GWAS associations

210 associations (top):

Study	Trait	p-value
GCST000133_2	HDL cholesterol	3.000000e-10
GCST000135_7	HDL cholesterol	1.000000e-10
GCST000288_8	HDL cholesterol	9.000000e-13
GCST000290_4	HDL cholesterol	1.000000e-09
GCST000755_30	HDL cholesterol	2.000000e-33
GCST000760_11	Cholesterol, total	3.000000e-27
GCST000805_10	HDL cholesterol	5.000000e-07
GCST000895_3	Whole-brain volume (Alzheimer’s disease interaction)	9.000000e-06
GCST000974_4	HDL cholesterol	5.000000e-07
GCST001237_2	HDL cholesterol	2.000000e-18
GCST001356_13	Gout	1.000000e-07
GCST001392_6	Lipid metabolism phenotypes	2.000000e-11
GCST001436_21	Metabolic syndrome	6.000000e-10
GCST001639_1	Metabolite levels	2.000000e-10
GCST001712_6	Myopia (pathological)	9.000000e-06
GCST001904_4	HDL cholesterol	6.000000e-26
GCST002127_8	Periodontitis (Mean PAL)	7.000000e-06
GCST002221_3	Cholesterol, total	6.000000e-53
GCST002223_4	HDL cholesterol	2.000000e-65
GCST002550_12	Allergic rhinitis	8.000000e-07
GCST002580_5	Intraocular pressure	3.000000e-11
GCST002581_1	Glaucoma (high intraocular pressure)	7.000000e-14
GCST002582_4	Glaucoma (primary open-angle)	2.000000e-19
GCST002782_61	Waist-to-hip ratio adjusted for body mass index	3.000000e-08
GCST002782_87	Waist-to-hip ratio adjusted for body mass index	1.000000e-08
GCST002782_88	Waist-to-hip ratio adjusted for body mass index	1.000000e-08
GCST002782_89	Waist-to-hip ratio adjusted for body mass index	9.000000e-09
GCST002896_25	Cholesterol, total	2.000000e-22
GCST002899_18	HDL cholesterol	2.000000e-34
GCST002931_4	Aluminium levels	9.000000e-06

EFO canonical traits (30, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0005089	whole-brain volume
EFO:0004529	lipid measurement
EFO:0000195	metabolic syndrome
EFO:0004723	coronary artery calcification
EFO:0004207	pathological myopia
EFO:0004695	intraocular pressure measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:1001492	atrophic macular degeneration
EFO:0007806	total cholesterol change measurement
EFO:0005921	FEV change measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0004531	urate measurement
EFO:0010118	sphingomyelin measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004469	HOMA-B
EFO:0007986	reticulocyte count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D052456	Hypoalphalipoproteinemias	C16.320.565.398.500.330; C18.452.584.500.875.330; C18.452.584.563.500.330; C18.452.648.398.500.330
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650
D013631	Tangier Disease	C10.668.829.800.875; C16.320.565.398.500.330.750; C18.452.584.500.875.330.750; C18.452.584.563.500.330.750; C18.452.648.398.500.330.750
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362986 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12003906	Efficacy	3	atorvastatin;pravastatin;simvastatin	Hyperlipidemias
rs2230806	Efficacy	3	pravastatin	Coronary Disease
rs2230806	Efficacy	3	fenofibrate	Hypertriglyceridemia
rs2230806	Efficacy	3	atorvastatin
rs2230806	Efficacy	3	rosuvastatin
rs2230806	Efficacy	3	simvastatin
rs2230808	Efficacy	3	fenofibrate	Hypertriglyceridemia

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2230806	ABCA1	3	4.50	5	pravastatin;fenofibrate;atorvastatin;rosuvastatin;simvastatin
rs2230808	ABCA1	3	3.25	1	fenofibrate
rs2472507	ABCA1		0.00	0
rs2515629	ABCA1		0.00	0
rs3887137	ABCA1		0.00	0
rs4149297	ABCA1		0.00	0
rs12003906	ABCA1	3	3.50	1	atorvastatin;pravastatin;simvastatin
rs769705621	ABCA1		0.00	0
rs2472434	ABCA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

226 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
T0901317	increases expression, increases reaction, decreases reaction, affects cotreatment	15
22-hydroxycholesterol	increases expression, decreases reaction, affects cotreatment	7
GW 3965	decreases expression, decreases reaction, increases expression	7
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	6
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	5
Cholesterol	increases reaction, increases expression, decreases reaction, increases export, affects reaction (+4 more)	5
Particulate Matter	increases expression, affects cotreatment, decreases reaction, increases abundance	5
tributyltin	affects cotreatment, decreases reaction, increases expression	4
perfluorooctane sulfonic acid	decreases expression, increases expression	4
27-hydroxycholesterol	increases expression, increases abundance	4
Rosiglitazone	affects response to substance, affects cotreatment, increases expression	4
Resveratrol	increases secretion, decreases reaction, increases expression, increases reaction, decreases expression	4
Arsenic Trioxide	affects cotreatment, decreases reaction, increases expression, decreases expression	4
Oxygen	affects expression, affects reaction, decreases expression, increases expression	4
Cyclosporine	decreases expression, affects cotreatment	4
Pioglitazone	increases expression, affects expression	3
Alitretinoin	affects cotreatment, increases expression, decreases reaction	3
Air Pollutants	decreases reaction, decreases expression, increases abundance, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Methotrexate	affects cotreatment, increases expression, decreases expression, decreases reaction	3
Quercetin	decreases expression, increases expression, affects cotreatment	3
Aflatoxin B1	increases methylation, affects expression, decreases expression	3
Oleic Acid	increases degradation, increases phosphorylation, affects cotreatment, affects expression, decreases expression (+3 more)	3
Simvastatin	decreases expression, increases expression	3
bis(tri-n-butyltin)oxide	increases expression	2
25-hydroxycholesterol	increases activity, increases expression, affects cotreatment, increases reaction, affects binding	2
sodium arsenite	increases expression, decreases expression, decreases reaction, increases methylation, increases abundance	2
24-hydroxycholesterol	increases expression	2
ZM 241385	decreases expression, decreases reaction, increases expression	2
UVI 3003	decreases reaction, increases expression	2

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5588852	Binding	Activation of ABCA1 (unknown origin) assessed as maximal efficacy relative to control	Nonlipogenic ABCA1 Inducers (NLAI) for Alzheimer’s Disease Validated in a Mouse Model Expressing Human APOE3/APOE4. — J Med Chem

Cellosaurus cell lines

23 cell lines: 8 induced pluripotent stem cell, 6 cancer cell line, 5 spontaneously immortalized cell line, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1RF	Abcam U-87MG ABCA1 KO	Cancer cell line	Male
CVCL_D1V0	Abcam A-549 ABCA1 KO	Cancer cell line	Male
CVCL_D1ZN	Abcam HCT 116 ABCA1 KO	Cancer cell line	Male
CVCL_D8DY	Ubigene ARPE-19 ABCA1 KO	Spontaneously immortalized cell line	Male
CVCL_E1E9	Ubigene U-87 MG ABCA1 KO	Cancer cell line	Male
CVCL_E6JD	HEK293H ABCA1 HA-KM	Transformed cell line	Female
CVCL_E6JE	HEK293H ABCA1 HA-MK	Transformed cell line	Female
CVCL_E6JF	HEK293H ABCA1 HA-MM	Transformed cell line	Female
CVCL_E6JG	HEK293H ABCA1 HA-WT	Transformed cell line	Female
CVCL_E6JH	MDCKII ABCA1 HA-KM	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen