ABCC1

Chr 16AD

ATP binding cassette subfamily C member 1 (ABCC1 blood group)

Also known as: ABC29, ABCC, DFNA77, GS-X, MRP, MRP1

NCBI Gene: 4363 ENSG00000103222 UniProt: P33527

The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 77MIM #618915

476

ClinVar variants

152

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— ABCC1

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Gene-Disease Validity (ClinGen)

autosomal dominant nonsyndromic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

152 Pathogenic / Likely Pathogenic· 290 VUS of 476 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

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.

0.40LOEUF

pLI 0.001

Z-score 5.85

OE 0.28 (0.20–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

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.

1.77Z-score

OE missense 0.84 (0.79–0.89)

782 obs / 934.6 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.0.28 (0.20–0.40)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.79–0.89)

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.1.12

0≤1.21.6

LoF obs/exp: 21 / 76.1Missense obs/exp: 782 / 934.6Syn Z: -1.93