ABCC1

Chr 16AD

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

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

ABCC1 encodes an ATP-binding cassette transporter that exports organic anions, drugs, glutathione conjugates, and other molecules from cells. Mutations cause autosomal dominant deafness (DFNA77), though the gene shows very low constraint to loss-of-function variants (pLI 0.001, LOEUF 0.397), suggesting the associated phenotype may be uncommon or incompletely penetrant. The protein plays roles in drug resistance and inflammatory responses through export of various substrates including leukotriene C4.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.401 OMIM phenotype
Clinical SummaryABCC1
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Gene-Disease Validity (ClinGen)
autosomal dominant nonsyndromic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.001
Z-score 5.85
OE 0.28 (0.200.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.77Z-score
OE missense 0.84 (0.790.89)
782 obs / 934.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.200.40)
00.351.4
Missense OE0.84 (0.790.89)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 21 / 76.1Missense obs/exp: 782 / 934.6Syn Z: -1.93
DN
0.76top 25%
GOF
0.78top 25%
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ABCC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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