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 OMIM: 158343

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.401 OMIM phenotype

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

1 unique Pathogenic / Likely Pathogenic· 150 VUS of 268 total submissions

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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.77Z-score

OE missense 0.84 (0.79–0.89)

782 obs / 934.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.20–0.40)

0≤0.351.4

Missense OE?0.84 (0.79–0.89)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

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

This gene — mechanism propensity

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

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS150

Likely Benign37

Benign17

Conflicting1

Pathogenic

150

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	142	8	0	150
Likely Benign	1	15	3	18	37
Benign	0	6	2	9	17
Conflicting	—				1
Total	1	164	13	27	206

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

View in ClinVar →

221 pathogenic / likely-pathogenic (of 378) ClinVar copy-number / structural variants overlap ABCC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →