ABCC2
protein-codingATP binding cassette subfamily C member 2, 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. This protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]
- CMOAT
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~70.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009380
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009380
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009380
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal
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
Comments: Heterozygotes may display manifestations; The presence of variants may have pharmacogenomic implications
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ABCC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000392.5. 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 | 20 | 345 | 5 | 370 | ||
| missense | 5 | 17 | 357 | 52 | 3 | 434 |
| nonsense | 38 | 19 | 57 | |||
| start loss | 1 | 1 | ||||
| frameshift | 60 | 26 | 2 | 88 | ||
| splice donor/acceptor (+/-2bp) | 4 | 47 | 8 | 59 | ||
| Total | 107 | 109 | 388 | 397 | 8 | 1009 |
Highest pathogenic variant AF is 0.0005427227
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000383.2 | 32 | MANE Select | |
| Ensembl | ENSP00000497274.1 | 32 | MANE Select | |
| Ensembl | ENSP00000497248.1 | 7 | Standard | |
| Ensembl | ENSP00000497778.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Methotrexate Pathway, Pharmacokinetics
- Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
- Bile secretion - Homo sapiens (human)
- ABC transporters - Homo sapiens (human)
- Doxorubicin Pathway, Pharmacokinetics
Biological Process
- bilirubin transport
- transmembrane transport
- ATP hydrolysis coupled anion transmembrane transport
Molecular Function
- protein binding
- ATP binding
- organic anion transmembrane transporter activity
- bilirubin transmembrane transporter activity
- ATPase activity, coupled to transmembrane movement of substances
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell surface
- membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370449
- Coding exons
- 32
- Length
- 69461
- Individuals with no LoFs
- 125193
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 553
- Defined
- 125748
- p
- 0.00221
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.995 | 863 | 785 | 1.10 | 0.0000433 | 10132 |
| Missense (PolyPhen) | 317 | 301.37 | 1.0518 | 3897 | ||
| Synonymous | -0.406 | 315 | 306 | 1.03 | 0.0000170 | 3062 |
| Loss of Function | 0.381 | 73 | 76.6 | 0.953 | 0.00000430 | 883 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0030 | 0.0029 | notable |
| Finnish | 0.0086 | 0.0086 | notable |
| European (Non-Finnish) | 0.0012 | 0.0011 | notable |
| South Asian | 0.0034 | 0.0034 | notable |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.;
Recessive Scores
- pRec
- 0.239
Intolerance Scores
- LoFtool
- 0.0978
- RVIS EVS
- 0.96
- RVIS percentile EVS
- 90.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.782
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |