ABCA5

Summary

ABCA5 (ATP binding cassette subfamily A member 5, HGNC:35) is a protein-coding gene on chromosome 17q24.3, encoding Cholesterol transporter ABCA5 (Q8WWZ7). Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport.

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, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described.

Source: NCBI Gene 23461 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gingival fibromatosis-hypertrichosis syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 299 total — 2 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_172232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35
Approved symbol	ABCA5
Name	ATP binding cassette subfamily A member 5
Location	17q24.3
Locus type	gene with protein product
Status	Approved
Aliases	EST90625
Ensembl gene	ENSG00000154265
Ensembl biotype	protein_coding
OMIM	612503
Entrez	23461

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 non_stop_decay, 1 protein_coding_CDS_not_defined

ENST00000392676, ENST00000586601, ENST00000586811, ENST00000586995, ENST00000587607, ENST00000588106, ENST00000588665, ENST00000588877, ENST00000589609, ENST00000589975, ENST00000591234, ENST00000592568, ENST00000593153, ENST00000593253, ENST00000915134, ENST00000957310, ENST00000957311

RefSeq mRNA: 2 — MANE Select: NM_172232 NM_018672, NM_172232

CCDS: CCDS11685

Canonical transcript exons

ENST00000392676 — 39 exons

Exon	Start	End
ENSE00001186911	69306725	69306954
ENSE00001186915	69308280	69308368
ENSE00001186922	69309262	69309423
ENSE00001186928	69313092	69313296
ENSE00001260588	69314314	69314430
ENSE00001365141	69285898	69286037
ENSE00001368687	69304669	69304810
ENSE00001368869	69286221	69286311
ENSE00001369458	69289862	69290037
ENSE00001370544	69289177	69289296
ENSE00001373572	69302718	69302906
ENSE00001374099	69291216	69291326
ENSE00001377399	69297191	69297359
ENSE00001388270	69301139	69301286
ENSE00001391181	69287613	69287751
ENSE00001391224	69294655	69294713
ENSE00002853180	69244311	69247644
ENSE00002855717	69327052	69327133
ENSE00003468748	69264735	69264905
ENSE00003477095	69248262	69248317
ENSE00003483251	69283953	69284072
ENSE00003486764	69273959	69274128
ENSE00003495314	69260338	69260412
ENSE00003497178	69255733	69255850
ENSE00003503103	69255543	69255634
ENSE00003531640	69259706	69259797
ENSE00003534159	69250472	69250621
ENSE00003541243	69251747	69251866
ENSE00003550126	69261125	69261259
ENSE00003572457	69253573	69253667
ENSE00003577060	69253794	69253869
ENSE00003593264	69254315	69254490
ENSE00003616028	69261635	69261748
ENSE00003632783	69267943	69268056
ENSE00003633129	69256157	69256283
ENSE00003650763	69249905	69249984
ENSE00003678842	69271162	69271289
ENSE00003683930	69277641	69277842
ENSE00003691194	69270613	69270750

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6866 / max 337.2032, expressed in 1562 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167798	11.2387	1534
167799	0.7930	405
167794	0.3049	127
167800	0.1755	53
167797	0.1218	53
167792	0.0527	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.57	gold quality
body of pancreas	UBERON:0001150	97.09	gold quality
calcaneal tendon	UBERON:0003701	96.83	gold quality
gastrocnemius	UBERON:0001388	96.07	gold quality
cerebellar hemisphere	UBERON:0002245	95.60	gold quality
bronchial epithelial cell	CL:0002328	95.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.55	gold quality
cerebellar cortex	UBERON:0002129	95.51	gold quality
upper leg skin	UBERON:0004262	95.34	gold quality
muscle of leg	UBERON:0001383	95.31	gold quality
right lobe of liver	UBERON:0001114	94.96	gold quality
jejunal mucosa	UBERON:0000399	94.61	gold quality
skin of abdomen	UBERON:0001416	94.51	gold quality
pituitary gland	UBERON:0000007	94.48	gold quality
skin of hip	UBERON:0001554	94.21	gold quality
skin of leg	UBERON:0001511	94.05	gold quality
muscle organ	UBERON:0001630	94.03	gold quality
adenohypophysis	UBERON:0002196	94.02	gold quality
gluteal muscle	UBERON:0002000	94.01	gold quality
epithelium of bronchus	UBERON:0002031	94.00	gold quality
cerebellum	UBERON:0002037	93.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.77	gold quality
pancreas	UBERON:0001264	93.74	gold quality
lower esophagus mucosa	UBERON:0035834	93.73	gold quality
deltoid	UBERON:0001476	93.67	gold quality
bronchus	UBERON:0002185	93.62	gold quality
tibia	UBERON:0000979	93.48	gold quality
tibialis anterior	UBERON:0001385	93.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.05	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1896.86
E-CURD-119	yes	1876.80
E-GEOD-98556	yes	518.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting ABCA5, 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-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666

Literature-anchored findings (GeneRIF, showing 12)

• Cloning of ABCA5 and detection of a splice variant. (PMID:12504089)
• ABCA5 may have a role in prostatic intraepithelial neoplasia (PMID:17289887)
• There is a correlation of induction of ABCA5 and mRNA with differentiation of colonic neoplasms. (PMID:17541169)
• The ABCB5 gene may be related to the properties of chemoresistance and aggressiveness of melanoma (PMID:20487690)
• Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma. (PMID:22870217)
• The expression of ABCA5 was significantly elevated in parkinson disease brains compared to age- and gender-matched control brains. (PMID:23939407)
• our findings support ABCA5 as a gene underlying the congenital generalized hypertrichosis terminalis phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth. (PMID:24831815)
• This report represents the first extensive expression and functional study of ABCA5 in the human brain and our data suggest a plausible function of ABCA5 in the brain as a cholesterol transporter associated with Abeta generation (PMID:25125465)
• Novel Mechanism of Cholesterol Transport by ABCA5 in Macrophages and Its Role in Dyslipidemia. (PMID:32687853)
• Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle. (PMID:33404706)
• Exome sequencing reveals the first intragenic deletion in ABCA5 underlying autosomal recessive hypertrichosis. (PMID:35150007)
• Cholesterol homeostasis in hair follicle keratinocytes is disrupted by impaired ABCA5 activity. (PMID:37348644)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Abca5	ENSMUSG00000018800
rattus_norvegicus	Abca5	ENSRNOG00000004378
drosophila_melanogaster	Eato	FBGN0028539
drosophila_melanogaster	CG1801	FBGN0031171
drosophila_melanogaster	CG8908	FBGN0034493
drosophila_melanogaster	CG31213	FBGN0051213
drosophila_melanogaster	ldd	FBGN0083956
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), ABCA1 (ENSG00000165029), ABCA3 (ENSG00000167972), ABCA13 (ENSG00000179869), ABCA4 (ENSG00000198691)

Protein

Protein identifiers

Cholesterol transporter ABCA5 — Q8WWZ7 (reviewed: Q8WWZ7)

Alternative names: ATP-binding cassette sub-family A member 5

All UniProt accessions (9): Q8WWZ7, A0A075B778, K7EJW6, K7EKS9, K7EMV2, K7ENF9, K7EPM3, K7EQ50, Q6N017

UniProt curated annotations — full annotation on UniProt →

Function. Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport. May play a role in the processing of autolysosomes.

Subcellular location. Golgi apparatus membrane. Lysosome membrane. Late endosome membrane. Cell membrane.

Tissue specificity. Ubiquitously expressed. Highly expressed in testis, skeletal muscle, kidney, liver and placenta. Expressed in both the epithelial and mesenchymal compartments, present within the outer root sheath (ORS) of the hair follicle as well as dermal sheath. Expressed in multiple regions of the brain, including the hippocampus, superior frontal and inferior temporal cortices. Strongly expressed in neurons and moderately in microglia, with only weak expression in astrocytes and oligodendrocytes.

Post-translational modifications. N-glycosylated.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWZ7-1	1	yes
Q8WWZ7-2	2, V20+16
Q8WWZ7-3	3

RefSeq proteins (2): NP_061142, NP_758424* (*=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), 1 shown:

• cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+) (RHEA:39051)

UniProt features (41 total): transmembrane region 15, sequence variant 7, sequence conflict 6, glycosylation site 3, splice variant 3, domain 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWZ7-F1	77.12	0.12

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): 514–521; 1333–1340

Glycosylation sites (3): 86, 458, 996

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1369062	ABC transporters in lipid homeostasis
R-HSA-382551	Transport of small molecules
R-HSA-382556	ABC-family protein mediated transport

MSigDB gene sets: 243 (showing top): GOBP_STEROL_HOMEOSTASIS, GOCC_VACUOLAR_MEMBRANE, FISCHER_G1_S_CELL_CYCLE, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, KEGG_ABC_TRANSPORTERS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, GOBP_CHOLESTEROL_EFFLUX, GOBP_PROTEIN_LIPID_COMPLEX_ORGANIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

GO Biological Process (10): lipid transport (GO:0006869), cholesterol metabolic process (GO:0008203), negative regulation of macrophage derived foam cell differentiation (GO:0010745), regulation of cholesterol efflux (GO:0010874), cholesterol efflux (GO:0033344), high-density lipoprotein particle remodeling (GO:0034375), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), positive regulation of reverse cholesterol transport (GO:1903064), transmembrane transport (GO:0055085)

GO Molecular Function (6): lipid carrier activity (GO:0005319), ATP binding (GO:0005524), 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 (9): Golgi membrane (GO:0000139), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), plasma membrane (GO:0005886), late endosome membrane (GO:0031902), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ABC-family protein mediated transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cholesterol transport	2
ATP-dependent activity	2
endomembrane system	2
lipid localization	1
sterol metabolic process	1
secondary alcohol metabolic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
regulation of cholesterol transport	1
cholesterol efflux	1
plasma lipoprotein particle remodeling	1
sterol homeostasis	1
positive regulation of cholesterol transport	1
reverse cholesterol transport	1
regulation of reverse cholesterol transport	1
cellular process	1
molecular carrier activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	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
Golgi apparatus	1
bounding membrane of organelle	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endosome	1
membrane	1
cell periphery	1
late endosome	1
endosome membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA5	ELP6	Q0PNE2	810
ABCA5	ABCD4	O14678	608
ABCA5	MAP2K6	P52564	595
ABCA5	ABCF3	Q9NUQ8	551
ABCA5	ABCF1	Q8NE71	475
ABCA5	TRAPPC1	Q9Y5R8	416
ABCA5	HMGCS1	Q01581	394
ABCA5	ABCA2	Q9BZC7	365
ABCA5	ABCB1	P08183	350
ABCA5	CCDC3	Q9BQI4	348
ABCA5	ABCC8	Q09428	336
ABCA5	ABCF2	Q9UG63	322
ABCA5	ABCB7	O75027	318
ABCA5	ABCB6	Q9NP58	318
ABCA5	ABCA7	Q8IZY2	316

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CYP2E1	ABCA5	psi-mi:“MI:0915”(physical association)	0.370
NR4A1	ABCA5	psi-mi:“MI:0915”(physical association)	0.370
MAPT	LANCL1	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
MFSD11	PLD2	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): ABCA5 (Affinity Capture-MS), ABCA5 (Affinity Capture-MS), ABCA5 (Affinity Capture-MS), ABCA5 (Co-localization), ABCA5 (Cross-Linking-MS (XL-MS)), ABCA5 (Affinity Capture-MS), ABCA5 (Cross-Linking-MS (XL-MS)), STXBP5 (Co-fractionation), ABCA5 (Affinity Capture-MS), ABCA5 (Affinity Capture-MS), ABCA5 (Affinity Capture-MS), CYP2E1 (Two-hybrid), NR4A1 (Two-hybrid)

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: A0A059J0G5, A0A0M3R8G1, A0A1L9WQK0, A0A1U8QKX8, A0A1U8QT10, A0A1V0QSE4, A0A1V1GB10, A0A1Y0BRF0, A0A2H1A768, A0A2U8U2K9, A0A481WQK1, A0A4P8GG95, A0A8K1AW53, A1C8C8, A1CFM0, B6HV31, B6RAL1, B8NDS8, B9G5Y5, D3GE74, D4AYW0, D4GSY7, E9PU17, E9PX95, E9RBG1, F2PLH2, F2RSQ6, F2SG60, F2SHL1, G3JF11, I1RL06, J9VME1, J9VPA2, M2UCE5, O06967, O42690, O65934, O74208, O74676, P0A9V1

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	2
Likely pathogenic	6
Uncertain significance	201
Likely benign	40
Benign	14

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
4070980	NM_172232.4(ABCA5):c.248del (p.Pro83fs)	Pathogenic
4845884	NM_172232.4(ABCA5):c.4504C>T (p.Arg1502Ter)	Pathogenic
1690962	NM_172232.4(ABCA5):c.2167_2168del (p.Leu723fs)	Likely pathogenic
2445995	NM_172232.4(ABCA5):c.2569C>T (p.Arg857Cys)	Likely pathogenic
3065858	NM_172232.4(ABCA5):c.1632_1633del (p.Arg544fs)	Likely pathogenic
3065938	NM_172232.4(ABCA5):c.4315C>T (p.Arg1439Ter)	Likely pathogenic
4849385	NM_172232.4(ABCA5):c.4270G>T (p.Glu1424Ter)	Likely pathogenic
4849432	NM_172232.4(ABCA5):c.977_978del (p.His326fs)	Likely pathogenic

SpliceAI

6279 predictions. Top by Δscore:

Variant	Effect	Δscore
17:69248318:C:CC	acceptor_gain	1.0000
17:69249980:AAAAA:A	acceptor_gain	1.0000
17:69249981:AAAA:A	acceptor_gain	1.0000
17:69249982:AAA:A	acceptor_gain	1.0000
17:69249983:AA:A	acceptor_gain	1.0000
17:69249985:C:CC	acceptor_gain	1.0000
17:69250466:TTTTA:T	donor_loss	1.0000
17:69250467:TTTAC:T	donor_loss	1.0000
17:69250468:TTACC:T	donor_loss	1.0000
17:69250469:TAC:T	donor_loss	1.0000
17:69250470:ACCT:A	donor_loss	1.0000
17:69250471:C:A	donor_loss	1.0000
17:69250475:T:A	donor_gain	1.0000
17:69250617:TACAT:T	acceptor_gain	1.0000
17:69250619:CAT:C	acceptor_gain	1.0000
17:69250622:C:CC	acceptor_gain	1.0000
17:69251750:AACTG:A	donor_gain	1.0000
17:69251751:A:C	donor_gain	1.0000
17:69251774:A:AC	donor_gain	1.0000
17:69251775:C:CC	donor_gain	1.0000
17:69251775:CTCGA:C	donor_gain	1.0000
17:69251776:TCGAT:T	donor_gain	1.0000
17:69251777:CGATC:C	donor_gain	1.0000
17:69253663:CACAA:C	acceptor_gain	1.0000
17:69253665:CAA:C	acceptor_gain	1.0000
17:69253668:C:CC	acceptor_gain	1.0000
17:69253672:A:C	acceptor_gain	1.0000
17:69253790:GTACC:G	donor_loss	1.0000
17:69253792:A:AC	donor_gain	1.0000
17:69253792:A:AG	donor_loss	1.0000

AlphaMissense

10866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:69251777:C:G	R1502P	1.000
17:69250598:A:G	L1520P	0.999
17:69250613:C:T	G1515E	0.999
17:69251771:G:T	A1504D	0.999
17:69251772:C:G	A1504P	0.999
17:69251782:A:C	C1500W	0.999
17:69255595:T:A	K1339I	0.999
17:69255598:C:T	G1338D	0.999
17:69255613:C:T	G1333D	0.999
17:69255614:C:G	G1333R	0.999
17:69255622:C:T	G1330E	0.999
17:69286224:A:G	L710P	0.999
17:69286250:T:A	K701N	0.999
17:69286250:T:G	K701N	0.999
17:69286251:T:A	K701I	0.999
17:69286254:A:G	L700P	0.999
17:69286254:A:T	L700H	0.999
17:69286269:C:T	G695D	0.999
17:69286270:C:G	G695R	0.999
17:69287628:C:G	A676P	0.999
17:69291290:G:T	A511D	0.999
17:69249913:A:G	L1586P	0.998
17:69250594:C:A	K1521N	0.998
17:69250594:C:G	K1521N	0.998
17:69250613:C:A	G1515V	0.998
17:69250614:C:G	G1515R	0.998
17:69250614:C:T	G1515R	0.998
17:69251783:C:T	C1500Y	0.998
17:69251796:C:G	A1496P	0.998
17:69251819:A:G	L1488P	0.998

dbSNP variants (sampled 300 via entrez): RS1000040025 (17:69312433 T>A), RS1000114857 (17:69275791 G>A), RS1000125531 (17:69325303 T>C,G), RS1000154388 (17:69312693 C>A), RS1000237084 (17:69306337 T>C), RS1000272967 (17:69244688 A>T), RS1000301517 (17:69252791 G>A), RS1000353400 (17:69253268 T>C), RS1000435964 (17:69269629 A>T), RS1000450061 (17:69276861 C>G,T), RS1000454820 (17:69276481 A>G), RS1000559304 (17:69272269 T>C,G), RS1000596509 (17:69276538 G>C), RS1000778712 (17:69315943 A>T), RS1000799920 (17:69270975 G>A)

Disease associations

OMIM: gene MIM:612503 | disease phenotypes: MIM:135400, MIM:143890

GenCC curated gene-disease

Disease	Classification	Inheritance
gingival fibromatosis-hypertrichosis syndrome	Supportive	Autosomal dominant
ventricular tachycardia, familial	Limited	Unknown

Mondo (3): gingival fibromatosis-hypertrichosis syndrome (MONDO:0007610), hypercholesterolemia, familial, 1 (MONDO:0007750), ventricular tachycardia, familial (MONDO:0008648)

Orphanet (2): Gingival fibromatosis-hypertrichosis syndrome (Orphanet:2026), Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000169	Gingival fibromatosis
HP:0000212	Gingival overgrowth
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000414	Bulbous nose
HP:0000494	Downslanted palpebral fissures
HP:0000574	Thick eyebrow
HP:0000664	Synophrys
HP:0000684	Delayed eruption of teeth
HP:0000998	Hypertrichosis
HP:0001007	Hirsutism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0002230	Generalized hirsutism
HP:0002353	EEG abnormality
HP:0004540	Congenital, generalized hypertrichosis
HP:0009928	Thick nasal alae
HP:0012810	Wide nasal base
HP:0100543	Cognitive impairment

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007450_2	Normal facial asymmetry (deformation magnitude)	3.000000e-06
GCST009391_1537	Metabolite levels	3.000000e-07
GCST010083_146	Hemoglobin levels	4.000000e-28
GCST011367_12	Iron status biomarkers (iron levels)	1.000000e-09
GCST012100_6	Hypertrophic cardiomyopathy (sarcomere positive)	8.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009751	facial asymmetry measurement
EFO:0010510	NG-monomethyl-arginine measurement
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565016	Hypertrichosis Terminalis, Generalized, with or without Gingival Hyperplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases reaction, affects cotreatment, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	3
Benzo(a)pyrene	increases expression, increases methylation	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Cyclosporine	increases expression, affects expression, decreases expression	3
manganese chloride	decreases expression, affects cotreatment, increases abundance	2
entinostat	affects cotreatment, decreases expression	2
(+)-JQ1 compound	increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Doxorubicin	affects expression, decreases expression	2
Manganese	decreases expression, affects cotreatment, increases abundance	2
Aflatoxin B1	decreases expression	2
OTX015	increases expression	1
mivebresib	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
arsenite	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases 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