GeneBe

ABCC1

protein-coding

ATP binding cassette subfamily C member 1, the group of ATP binding cassette subfamily C

Gene summary

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]

Previous symbols:
  • MRP
  • MRP1

MANE transcript

NM_004996.4

Inheritance

AD

ClinVar variants

P:1U:186B:65

Top phenotype

Deafness, autosomal dominant 77

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr16:15,949,138-16,143,257

External References & Databases

Ensembl (ENSG00000103222)NCBI Gene (4363)OMIM (158343)HGNC:51GenCCUniProt (P33527)AlphaFoldClinVar (ABCC1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~194.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant nonsyndromic hearing lossLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: ClinGen

ABCC1 was first reported in relation to autosomal dominant nonsyndromic hearing loss in 2019 (Li et al., PMID: 31273342). 3 missense variants that have been reported in 3 probands in one publication (PMID: 31273342) are included in this curation. The variant segregated with disease in 10 members of one family. The affected individuals present with moderate to profound postlingual nonsyndromic hearing loss. The mechanism of pathogenicity is unclear. This gene-disease relationship is also supported by an expression study demonstrating ABCC1 localization on the stria vascularis as well as auditory nerves with a cytomembrane distribution (PMID: 31273342). Mouse models have also suggested a role for this gene in hearing loss, but relevant phenotypes were only observed following noise exposure (PMIDs: 38870779, 38951883). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Hearing Loss GCEP on the meeting date October 8, 2025 (SOP Version 11).

hearing loss, autosomal dominant 77MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030058

Submitter: PanelApp Australia

autosomal dominant nonsyndromic hearing lossSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: Orphanet

hearing loss, autosomal dominant 77LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030058

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Deafness, autosomal dominant 77AD

Manifestation: Audiologic/Otolaryngologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31273342Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCC1 variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 168
not providedTotal: 50
ABCC1-related disorderTotal: 12
Hearing loss, autosomal dominant 77Total: 6
Familial cancer of breastTotal: 3
Autosomal dominant nonsyndromic hearing lossTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004996.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
33
clinvar
9
clinvar
 51
missense
1
clinvar
165
clinvar
18
clinvar
5
clinvar
 189
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
11
clinvar
 11
Total101865114252

Highest pathogenic variant AF is 0.000034073913

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 94 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004996.4RefSeqNP_004987.231MANE Select
ENST00000399410.8EnsemblENSP00000382342.331MANE Select
NM_001438715.1RefSeqNP_001425644.129Standard
NM_001438717.1RefSeqNP_001425646.128Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Methotrexate Pathway (Brain Cell), Pharmacokinetics
  • Methotrexate Pathway, Pharmacokinetics
  • Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
  • Vitamin digestion and absorption - Homo sapiens (human)
  • ABC transporters - Homo sapiens (human)

Biological Process

  • leukotriene metabolic process
  • drug transmembrane transport
  • cobalamin metabolic process
  • cobalamin transport
  • glutathione transmembrane transport

Molecular Function

  • phospholipid-translocating ATPase activity
  • transporter activity
  • ATP binding
  • xenobiotic transmembrane transporting ATPase activity
  • cobalamin-transporting ATPase activity

Cellular Component

  • vacuolar membrane
  • plasma membrane
  • integral component of plasma membrane
  • membrane
  • basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000399410
Coding exons
31
Length
193498
Individuals with no LoFs
124854
Homozygous LoFs
0
Heterozygous LoFs
56
Defined
124910
p
0.000224
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.777829350.8370.00005949995
Missense (PolyPhen)230371.430.619233873
Synonymous-1.934574071.120.00002903053
Loss of Function5.852176.10.2760.00000392854

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000390.00038rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.0000560.000056rare
Finnish0.000330.00032rare
European (Non-Finnish)0.000290.00029rare
South Asian0.0000980.000098rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency. {ECO:0000269|PubMed:10064732, ECO:0000269|PubMed:11114332, ECO:0000269|PubMed:16230346}.;

Intolerance Scores

LoFtool
0.0802
RVIS EVS
-0.84
RVIS percentile EVS
11.29

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.291

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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