ABCC3
protein-codingATP binding cassette subfamily C member 3, 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 protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~57.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ABCC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003786.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 9 | 1 | 12 | ||
| missense | 189 | 19 | 3 | 211 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 15 | 15 | ||||
| Total | 0 | 0 | 207 | 28 | 4 | 239 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003777.2 | 31 | MANE Select | |
| Ensembl | ENSP00000285238.8 | 31 | MANE Select | |
| RefSeq | NP_001137542.1 | 12 | Standard | |
| Ensembl | ENSP00000395160.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Methotrexate Pathway, Pharmacokinetics
- Bile secretion - Homo sapiens (human)
- ABC transporters - Homo sapiens (human)
- Codeine and Morphine Pathway, Pharmacokinetics
- Fluoropyrimidine Pathway, Pharmacokinetics
Biological Process
- bile acid and bile salt transport
- canalicular bile acid transport
- transmembrane transport
- ATP hydrolysis coupled anion transmembrane transport
Molecular Function
- ATP binding
- organic anion transmembrane transporter activity
- bile acid-exporting ATPase activity
- ATPase activity, coupled to transmembrane movement of substances
- ATPase-coupled anion transmembrane transporter activity
Cellular Component
- vacuolar membrane
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285238
- Coding exons
- 31
- Length
- 57476
- Individuals with no LoFs
- 125260
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 488
- Defined
- 125748
- p
- 0.00194
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.630 | 848 | 901 | 0.941 | 0.0000552 | 9849 |
| Missense (PolyPhen) | 288 | 321.22 | 0.89659 | 3591 | ||
| Synonymous | 1.59 | 346 | 386 | 0.897 | 0.0000239 | 3216 |
| Loss of Function | 2.29 | 52 | 73.1 | 0.711 | 0.00000358 | 799 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0013 | notable |
| Latino/Admixed American | 0.0025 | 0.0024 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0017 | 0.0017 | notable |
| Finnish | 0.0012 | 0.0012 | notable |
| European (Non-Finnish) | 0.0021 | 0.0021 | notable |
| South Asian | 0.0023 | 0.0023 | notable |
| Other | 0.0029 | 0.0029 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.279
Intolerance Scores
- LoFtool
- 0.0379
- RVIS EVS
- 0.69
- RVIS percentile EVS
- 85.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.581
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |