ABCA5

Chr 17AR

ATP binding cassette subfamily A member 5

Also known as: ABC13, DEL17q24, EST90625, HTC3, HTGH

NCBI Gene: 23461ENSG00000154265UniProt: Q8WWZ7

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Hypertrichosis, congenital generalized, with gingival hyperplasiaMIM #135400
AR
274
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ABCA5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 204 VUS of 274 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.78
OE 0.67 (0.54–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.37Z-score
OE missense 0.96 (0.91–1.02)
748 obs / 777.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.54–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.91–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 55 / 82.2Missense obs/exp: 748 / 777.3Syn Z: -0.20

ClinVar Variant Classifications

274 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic5
VUS204
Likely Benign40
Benign14
11
Pathogenic
5
Likely Pathogenic
204
VUS
40
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
10
0
11
Likely Pathogenic
2
1
2
0
5
VUS
1
198
5
0
204
Likely Benign
0
17
9
14
40
Benign
0
6
1
7
14
Total42222721274

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ABCA5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ABCA5-related hypertrichosis, congenital generalised, with gingival hyperplasia

limited
ARUndeterminedAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Hypertrichosis, congenital generalized, with gingival hyperplasia

MIM #135400

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cloning of human and rat ABCA5/Abca5 and detection of a human splice variant.
Petry F et al.·Biochem Biophys Res Commun
2003
Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis.
Chen J et al.·Drug Resist Updat
2024
Exome sequencing reveals the first intragenic deletion in ABCA5 underlying autosomal recessive hypertrichosis.
Raza R et al.·Clin Exp Dermatol
2022
Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.
DeStefano GM et al.·PLoS Genet
2014
ABC transporters are predictors of treatment failure in acute myeloid leukaemia.
Cerovska E et al.·Biomed Pharmacother
2024
Subcellular localization of rat Abca5, a rat ATP-binding-cassette transporter expressed in Leydig cells, and characterization of its splice variant apparently encoding a half-transporter.
Petry F et al.·Biochem J
2006
Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells.
Quezada CA et al.·Biol Pharm Bull
2008
ABCA transporter gene expression and poor outcome in epithelial ovarian cancer.
Hedditch EL et al.·J Natl Cancer Inst
2014
Proteomic analysis detects deregulated reverse cholesterol transport in human subjects with ST-segment elevation myocardial infarction.
Das AA et al.·J Proteomics
2020
Family-Based Whole Genome Sequencing Identified Novel Variants in ABCA5 Gene in a Patient with Idiopathic Ventricular Tachycardia.
Du Z et al.·Pediatr Cardiol
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools