ABCA8

Summary

ABCA8 (ATP binding cassette subfamily A member 8, HGNC:38) is a protein-coding gene on chromosome 17q24.2, encoding ABC-type organic anion transporter ABCA8 (O94911). Catalyzes ATP-dependent import of organic anions such as taurocholate and estrone sulfate.

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. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10351 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 299 total — 1 pathogenic
• MANE Select transcript: NM_001288985

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:38
Approved symbol	ABCA8
Name	ATP binding cassette subfamily A member 8
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0822
Ensembl gene	ENSG00000141338
Ensembl biotype	protein_coding
OMIM	612505
Entrez	10351

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 9 retained_intron, 1 non_stop_decay

ENST00000269080, ENST00000428549, ENST00000430352, ENST00000541225, ENST00000585531, ENST00000585850, ENST00000586292, ENST00000586539, ENST00000587206, ENST00000588458, ENST00000589533, ENST00000589980, ENST00000590359, ENST00000591459, ENST00000899806, ENST00000899807, ENST00000899808, ENST00000899809, ENST00000899810, ENST00000899811, ENST00000948182, ENST00000948183, ENST00000948184, ENST00000948185, ENST00000948186, ENST00000948187, ENST00000948188

RefSeq mRNA: 5 — MANE Select: NM_001288985 NM_001288985, NM_001288986, NM_001375771, NM_001375772, NM_007168

CCDS: CCDS11680, CCDS74138, CCDS74139

Canonical transcript exons

ENST00000586539 — 40 exons

Exon	Start	End
ENSE00001385939	68955219	68955392
ENSE00001780997	68867289	68868183
ENSE00002205413	68869700	68869779
ENSE00002217055	68949312	68949472
ENSE00002258106	68885196	68885315
ENSE00002286431	68887017	68887130
ENSE00002321664	68884331	68884396
ENSE00002446703	68876460	68876554
ENSE00002459437	68875614	68875733
ENSE00002471967	68875260	68875400
ENSE00002528742	68868301	68868356
ENSE00003460911	68929049	68929234
ENSE00003461220	68882599	68882719
ENSE00003475251	68921382	68921492
ENSE00003478601	68924701	68924869
ENSE00003483285	68918047	68918185
ENSE00003498295	68891489	68891596
ENSE00003498353	68933168	68933271
ENSE00003503982	68919301	68919476
ENSE00003528282	68907740	68907879
ENSE00003540787	68927916	68928063
ENSE00003546593	68906044	68906163
ENSE00003546904	68922242	68922300
ENSE00003547737	68883791	68883882
ENSE00003557270	68936951	68937115
ENSE00003567673	68917361	68917451
ENSE00003572731	68903301	68903499
ENSE00003582490	68894173	68894310
ENSE00003583435	68894880	68895013
ENSE00003601009	68877519	68877679
ENSE00003628684	68929561	68929702
ENSE00003631032	68876628	68876703
ENSE00003633983	68918427	68918546
ENSE00003652907	68887336	68887506
ENSE00003659153	68881120	68881211
ENSE00003669983	68940758	68940962
ENSE00003674032	68902713	68902879
ENSE00003683063	68932288	68932514
ENSE00003690626	68881863	68881980
ENSE00003692364	68941939	68942039

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.22.

FANTOM5 (CAGE): breadth broad, TPM avg 9.2346 / max 434.1932, expressed in 676 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167768	8.5355	672
167766	0.4129	149
167765	0.1537	98
167767	0.1325	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	99.22	gold quality
trigeminal ganglion	UBERON:0001675	99.03	gold quality
parietal pleura	UBERON:0002400	99.00	gold quality
pericardium	UBERON:0002407	98.92	gold quality
tibial nerve	UBERON:0001323	98.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.46	gold quality
germinal epithelium of ovary	UBERON:0001304	98.41	gold quality
corpus callosum	UBERON:0002336	98.40	gold quality
sural nerve	UBERON:0015488	98.21	gold quality
vena cava	UBERON:0004087	97.75	gold quality
olfactory bulb	UBERON:0002264	97.71	gold quality
myocardium	UBERON:0002349	97.59	gold quality
left ovary	UBERON:0002119	97.51	gold quality
heart right ventricle	UBERON:0002080	97.47	gold quality
diaphragm	UBERON:0001103	97.42	gold quality
right ovary	UBERON:0002118	97.27	gold quality
inferior vagus X ganglion	UBERON:0005363	97.14	gold quality
left ventricle myocardium	UBERON:0006566	96.89	gold quality
synovial joint	UBERON:0002217	96.85	gold quality
cranial nerve II	UBERON:0000941	96.80	gold quality
pleura	UBERON:0000977	96.80	gold quality
colonic epithelium	UBERON:0000397	96.74	gold quality
superficial temporal artery	UBERON:0001614	96.71	gold quality
inferior olivary complex	UBERON:0002127	96.61	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.56	gold quality
calcaneal tendon	UBERON:0003701	96.56	gold quality
cardiac atrium	UBERON:0002081	96.45	gold quality
right atrium auricular region	UBERON:0006631	96.25	gold quality
mucosa of stomach	UBERON:0001199	96.10	gold quality
right adrenal gland cortex	UBERON:0035827	95.96	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	1916.52
E-GEOD-134144	yes	1447.51
E-HCAD-36	yes	1138.52
E-HCAD-35	yes	75.21
E-GEOD-135922	yes	50.77
E-CURD-46	yes	24.64
E-MTAB-8410	yes	18.50
E-GEOD-84465	yes	10.35
E-MTAB-9543	no	2.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting ABCA8, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 11)

• Functional analysis of the transport properties of ABCA8. (PMID:12379217)
• SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels (PMID:21707071)
• ABCA8 is highly expressed in human brain and regulates lipid metabolism in oligodendrocytes, potentially playing a role in myelin formation and maintenance. (PMID:23560799)
• These data suggest a direct relationship between the levels of ABCA8 and the ectopic expression of alpha-syn and increased expression of p25alpha (PMID:23948991)
• Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate-binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels (PMID:28468577)
• ABCA8 facilitates cholesterol efflux and modulates HDL-cholesterol levels. (PMID:28882873)
• Study results suggest that mABCA8b/ABCA8 functions as a sinusoidal efflux transporter for at least cholesterol and taurocholate in mouse and human liver. (PMID:29300488)
• ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway. (PMID:32430024)
• Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma. (PMID:32685482)
• ABCA8 inhibits breast cancer cell proliferation by regulating the AMP activated protein kinase/mammalian target of rapamycin signaling pathway. (PMID:35191604)
• Tumour suppressor ABCA8 inhibits malignant progression of colorectal cancer via Wnt/beta-catenin pathway. (PMID:37968146)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	abca5	ENSDARG00000074041
mus_musculus	Abca8b	ENSMUSG00000020620
rattus_norvegicus	Abca8	ENSRNOG00000004040
drosophila_melanogaster	Eato	FBGN0028539
drosophila_melanogaster	CG1494	FBGN0031169
drosophila_melanogaster	Abca3	FBGN0031170
drosophila_melanogaster	CG1801	FBGN0031171
drosophila_melanogaster	CG8908	FBGN0034493
drosophila_melanogaster	CG6052	FBGN0036747
drosophila_melanogaster	CG31213	FBGN0051213
drosophila_melanogaster	ldd	FBGN0083956
drosophila_melanogaster	CG43672	FBGN0263747
caenorhabditis_elegans		WBGENE00000019
caenorhabditis_elegans	abt-2	WBGENE00000020
caenorhabditis_elegans		WBGENE00000022
caenorhabditis_elegans	abt-5	WBGENE00000023

Paralogs (11): ABCA7 (ENSG00000064687), ABCA2 (ENSG00000107331), ABCA12 (ENSG00000144452), ABCA9 (ENSG00000154258), ABCA6 (ENSG00000154262), ABCA10 (ENSG00000154263), ABCA5 (ENSG00000154265), ABCA1 (ENSG00000165029), ABCA3 (ENSG00000167972), ABCA13 (ENSG00000179869), ABCA4 (ENSG00000198691)

Protein

Protein identifiers

ABC-type organic anion transporter ABCA8 — O94911 (reviewed: O94911)

Alternative names: ATP-binding cassette sub-family A member 8

All UniProt accessions (4): A0A075B774, A0A0A0MSU4, O94911, K7ELK9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes ATP-dependent import of organic anions such as taurocholate and estrone sulfate. In vitro, also imports ochratoxin A. Also mediates cholesterol efflux independent of apolipoprotein, and plays a role in sphingomyelin production in oligodendrocytes. Catalyzes ATP-dependent efflux of cholesterol and taurocholate. Interaction with ABCA1 potentiates cholesterol efflux to lipid-free APOA1, which regulates high-density lipoprotein cholesterol levels.

Subunit / interactions. Interacts with ABCA1; this interaction potentiates cholesterol efflux.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Widely expressed with higher expression in heart, skeletal muscle and liver. Highly expressed in the superior frontal white matter and inferior temporal white matter.

Activity regulation. Dofequidar (MS-209) and ochratoxin A inhibited the 17beta-estradiol 17-O-(beta-D-glucuronate) influx. Cholesterol efflux is increased by extracellularly applied taurocholate.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O94911-3	3	yes
O94911-1	1
O94911-2	2

RefSeq proteins (5): NP_001275914, NP_001275915, NP_001362700, NP_001362701, NP_009099 (=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), 6 shown:

• cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+) (RHEA:39051)
• taurocholate(in) + ATP + H2O = taurocholate(out) + ADP + phosphate + H(+) (RHEA:50052)
• estrone 3-sulfate(out) + ATP + H2O = estrone 3-sulfate(in) + ADP + phosphate + H(+) (RHEA:65956)
• leukotriene C4(out) + ATP + H2O = leukotriene C4(in) + ADP + phosphate + H(+) (RHEA:65960)
• taurocholate(out) + ATP + H2O = taurocholate(in) + ADP + phosphate + H(+) (RHEA:65964)
• 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ADP + phosphate + H(+) (RHEA:65968)

UniProt features (46 total): glycosylation site 16, transmembrane region 14, sequence variant 9, domain 2, binding site 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94911-F1	78.67	0.17

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): 516–523; 1323–1330

Glycosylation sites (16): 71, 84, 194, 243, 484, 555, 616, 724, 797, 919, 948, 967, 1270, 1308, 1373, 1435

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 165 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, TATTATA_MIR374, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, TANG_SENESCENCE_TP53_TARGETS_UP

GO Biological Process (9): sphingomyelin biosynthetic process (GO:0006686), xenobiotic transmembrane transport (GO:0006855), lipid transport (GO:0006869), regulation of cholesterol efflux (GO:0010874), positive regulation of cholesterol efflux (GO:0010875), cholesterol transport (GO:0030301), cholesterol efflux (GO:0033344), xenobiotic transport (GO:0042908), transmembrane transport (GO:0055085)

GO Molecular Function (7): lipid carrier activity (GO:0005319), ATP binding (GO:0005524), ABC-type xenobiotic transporter activity (GO:0008559), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
cholesterol efflux	2
ATP-dependent activity	2
sphingomyelin metabolic process	1
phospholipid biosynthetic process	1
sphingolipid biosynthetic process	1
xenobiotic transport	1
transmembrane transport	1
lipid localization	1
regulation of cholesterol transport	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
sterol transport	1
cholesterol transport	1
cellular process	1
molecular carrier activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
xenobiotic transmembrane transporter activity	1
ABC-type transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA8	SLC22A8	Q8TCC7	785
ABCA8	ABCC1	P33527	517
ABCA8	ABCC9	O60706	503
ABCA8	ABCA1	O95477	497
ABCA8	SLCO1A2	P46721	473
ABCA8	SLC6A6	P31641	461
ABCA8	ABCF3	Q9NUQ8	447
ABCA8	MFAP4	P55083	442
ABCA8	ZCCHC24	Q8N2G6	437
ABCA8	SLC17A4	Q9Y2C5	436
ABCA8	ABCF1	Q8NE71	419
ABCA8	TYW1B	Q6NUM6	419
ABCA8	SPARCL1	Q14515	412
ABCA8	ABCC2	Q92887	408
ABCA8	CBLN2	Q8IUK8	404

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ABCA6	STX6	psi-mi:“MI:0914”(association)	0.350
ABCA8	CST4	psi-mi:“MI:0914”(association)	0.350
DISC1	ABCA8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): ABCA8 (Affinity Capture-MS), ABCA8 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), CST4 (Affinity Capture-MS), CST2 (Affinity Capture-MS), VCP (Cross-Linking-MS (XL-MS)), SARNP (Cross-Linking-MS (XL-MS)), SUMO2 (Cross-Linking-MS (XL-MS)), SNX18 (Cross-Linking-MS (XL-MS)), FZD6 (Cross-Linking-MS (XL-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: A0A0M3R8G1, A0A2P1AAV1, A0A481WQK1, A2WSH0, A3BXL8, B9G300, B9G5Y5, B9GDE5, C7J6G6, D3GE74, D4AYW0, E9PU17, H6WS93, H6WS94, O24367, O52618, O65934, O81016, O94911, P0A9V1, P0A9V2, P0A9V3, P0A9V4, P25371, P26050, P41234, P45082, P45843, P50332, P72335, Q0JLC5, Q13ZJ1, Q1BWI2, Q1LKJ2, Q2PCF1, Q2QV81, Q2SVP3, Q2W1R8, Q39GT7, Q3JSQ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	242
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4070981	NM_001288985.2(ABCA8):c.2337del (p.Ser779_Met780insTer)	Pathogenic

SpliceAI

5807 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68868357:C:CC	acceptor_gain	1.0000
17:68869660:T:C	donor_gain	1.0000
17:68869698:AC:A	donor_gain	1.0000
17:68869699:CC:C	donor_gain	1.0000
17:68869699:CCCTT:C	donor_gain	1.0000
17:68869779:CCTGA:C	acceptor_loss	1.0000
17:68869780:C:A	acceptor_loss	1.0000
17:68869781:T:A	acceptor_loss	1.0000
17:68875255:TTTAC:T	donor_loss	1.0000
17:68875257:TACCT:T	donor_loss	1.0000
17:68875259:C:CT	donor_loss	1.0000
17:68875263:T:A	donor_gain	1.0000
17:68875398:CAT:C	acceptor_gain	1.0000
17:68875408:A:C	acceptor_gain	1.0000
17:68875415:CATA:C	acceptor_gain	1.0000
17:68875416:A:AC	acceptor_gain	1.0000
17:68875416:A:C	acceptor_gain	1.0000
17:68875418:A:AC	acceptor_gain	1.0000
17:68875418:A:C	acceptor_gain	1.0000
17:68876704:C:CA	acceptor_loss	1.0000
17:68877552:AGC:A	donor_gain	1.0000
17:68881118:A:AC	donor_gain	1.0000
17:68881119:C:CC	donor_gain	1.0000
17:68881908:T:TA	donor_gain	1.0000
17:68881929:T:A	donor_gain	1.0000
17:68882594:TTTAC:T	donor_loss	1.0000
17:68882595:TTAC:T	donor_loss	1.0000
17:68882596:TA:T	donor_loss	1.0000
17:68882597:ACC:A	donor_loss	1.0000
17:68882598:C:A	donor_loss	1.0000

AlphaMissense

10679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:68881172:T:A	K1329I	0.994
17:68918081:A:C	S671R	0.992
17:68918081:A:T	S671R	0.992
17:68918083:T:G	S671R	0.992
17:68881191:C:G	G1323R	0.991
17:68881191:C:T	G1323R	0.991
17:68917390:C:A	K703N	0.991
17:68917390:C:G	K703N	0.991
17:68917394:A:G	L702P	0.991
17:68929079:A:C	S365R	0.991
17:68929079:A:T	S365R	0.991
17:68929081:T:G	S365R	0.991
17:68875377:A:G	L1505P	0.990
17:68881190:C:T	G1323E	0.990
17:68875639:C:G	A1489P	0.988
17:68875663:C:G	A1481P	0.988
17:68921456:G:T	A513E	0.988
17:68881168:G:C	S1330R	0.987
17:68881168:G:T	S1330R	0.987
17:68881170:T:G	S1330R	0.987
17:68918062:C:G	A678P	0.987
17:68875657:C:G	A1483P	0.986
17:68875644:C:G	R1487P	0.985
17:68876537:G:C	S1431R	0.985
17:68876537:G:T	S1431R	0.985
17:68876539:T:G	S1431R	0.985
17:68881179:C:G	A1327P	0.985
17:68894239:A:C	S990R	0.985
17:68894239:A:T	S990R	0.985
17:68894241:T:G	S990R	0.985

dbSNP variants (sampled 300 via entrez): RS1000023742 (17:68930339 T>C), RS1000024467 (17:68873168 A>C,T), RS1000057253 (17:68923408 C>G,T), RS1000111326 (17:68888614 C>CTA), RS1000123481 (17:68920315 C>G), RS1000133226 (17:68880398 C>T), RS1000145416 (17:68940696 C>T), RS1000186345 (17:68922822 T>C), RS1000222063 (17:68946887 G>T), RS1000230497 (17:68874606 T>C), RS1000274358 (17:68947962 T>G), RS1000356615 (17:68867859 T>C,G), RS1000357714 (17:68944070 C>T), RS1000393348 (17:68953104 G>A,C), RS1000397357 (17:68955491 T>C)

Disease associations

OMIM: gene MIM:612505 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000755_45	HDL cholesterol	2.000000e-10
GCST002223_35	HDL cholesterol	1.000000e-12
GCST002898_37	LDL cholesterol	2.000000e-18
GCST003214_13	Cholesterol, total	2.000000e-06
GCST003815_55	Late-onset Alzheimer’s disease	8.000000e-06
GCST004232_52	HDL cholesterol levels	2.000000e-15
GCST005196_225	Coronary artery disease	2.000000e-06
GCST005981_5	Phosphorus levels	1.000000e-08
GCST008196_3	Soluble VCAM-1 levels	1.000000e-13
GCST008260_14	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	3.000000e-09
GCST010241_178	Apolipoprotein A1 levels	5.000000e-30
GCST010242_278	HDL cholesterol levels	3.000000e-30
GCST010243_61	Apolipoprotein B levels	3.000000e-08
GCST010500_8	T-Cell Immunoglobulin and Mucin domain 1 levels	6.000000e-10
GCST011348_51	High density lipoprotein cholesterol levels	8.000000e-09
GCST012490_652	Femur bone mineral density x serum urate levels interaction	7.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0004861	phosphorus measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0010812	T-cell immunoglobulin and mucin domain 1 measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11656365	ABCA8		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases mutagenesis, affects methylation	4
sodium arsenite	affects methylation, decreases expression, increases expression	3
Estradiol	decreases expression, affects cotreatment	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
perfluorooctane sulfonic acid	decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Cyclosporine	decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
estrone sulfate	affects transport	1
butyraldehyde	decreases expression	1
estradiol-17 beta-glucuronide	increases uptake, affects reaction, decreases reaction	1
ochratoxin A	affects transport, decreases reaction, increases uptake	1
verlukast	decreases reaction, increases uptake	1
dofequidar	decreases reaction, increases uptake	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
licochalcone B	decreases expression	1
incobotulinumtoxinA	increases expression	1
Docetaxel	decreases response to substance, increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Adenosine Triphosphate	affects reaction, increases uptake	1
Air Pollutants	increases abundance, decreases expression	1
Digoxin	decreases reaction, increases uptake	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	increases expression	1
Nickel	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab