ABCC3: ATP Binding Cassette Subfamily C Member 3
Multidrug Resistance-Associated Protein 3 (MRP3) – Transporter, Pharmacogenomics, and Disease Associations
Gene Information Card
| Symbol | ABCC3 |
|---|---|
| Full Name | ATP Binding Cassette Subfamily C Member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 8714 ncbi.nlm.nih.gov/gene/8714 |
| Ensembl ID | ENSG00000108846 |
| UniProt ID | O15438 |
| OMIM ID | 604323 |
| HGNC ID | 54 |
| Aliases | MRP3, ABC31, MOAT-D, cMOAT2 |
Description
ABCC3 (ATP Binding Cassette Subfamily C Member 3) encodes multidrug resistance-associated protein 3 (MRP3), an ATP-dependent organic anion transporter. MRP3 mediates the efflux of glucuronide, sulfate, and glutathione conjugates, bile acids, and various drugs. It is expressed in liver, intestine, kidney, and adrenal gland, and plays roles in detoxification, drug disposition, and bile acid transport. Variants in ABCC3 are associated with altered drug response, cholestasis, and cancer prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cholestasis, progressive familial intrahepatic 2 (PFIC2) modifier | ABCC3 may compensate for BSEP deficiency by exporting bile acids; variants influence disease severity | PMID: 17461452 |
| Drug-induced liver injury (DILI) | ABCC3 polymorphisms affect hepatic transport of drug conjugates, altering susceptibility | PMID: 23974896 |
| Hepatocellular carcinoma | Overexpression of MRP3 confers chemoresistance to sorafenib and other agents | PMID: 25695677 |
| Colorectal cancer | High ABCC3 expression associated with poor prognosis and resistance to 5-fluorouracil | PMID: 27323851 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Adrenal gland | 8.2 | Medium |
| Kidney | 6.1 | Medium |
| Small intestine | 5.8 | Medium |
| Colon | 4.3 | Low |
| Lung | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line; high MRP3 expression |
| Caco-2 | 9.7 | Colorectal adenocarcinoma; moderate expression |
| A549 | 3.4 | Lung carcinoma; low expression |
| MCF7 | 1.2 | Breast cancer; low baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.211G>A (p.Val71Ile) | Missense | 0.5% (gnomAD) | Reduced transport activity for estradiol-17β-glucuronide |
| c.1331T>C (p.Ile444Thr) | Missense | 1.2% (gnomAD) | Altered substrate specificity; associated with DILI risk |
| c.3890A>G (p.Asn1297Ser) | Missense | 0.8% (gnomAD) | Decreased protein stability; linked to PFIC modifier phenotype |
Mutation functional classification
Loss of Function (LOF)
c.211G>A (p.Val71Ile) and c.3890A>G (p.Asn1297Ser) reduce transport activity or protein stability, leading to impaired efflux of organic anions.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in ABCC3.
Dominant Negative (DN)
No dominant-negative mutations described for ABCC3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ABC transporters (KEGG: hsa02010)
• Bile secretion (KEGG: hsa04976)
• Drug metabolism - other enzymes (KEGG: hsa00983)
• Glutathione metabolism (KEGG: hsa00480)
Protein Summary
MRP3 (ABCC3) is a 1527-amino acid transmembrane protein with two nucleotide-binding domains (NBDs) and three membrane-spanning domains (MSDs). It localizes to the basolateral membrane of hepatocytes, enterocytes, and renal tubular cells. MRP3 transports glucuronide and sulfate conjugates, bile acids, and anticancer drugs (e.g., etoposide, methotrexate). Its expression is induced by xenobiotics via nuclear receptors (e.g., PXR, CAR). MRP3 contributes to drug resistance in cancer and modulates bile acid homeostasis in cholestatic liver disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCC3 Knockout HEK293 Cell Line | EDJ-KQ6337 | Human | 8714 | Details Get a Quote |
| ABCC3 Knockout A-549 Cell Line | EDJ-KQ30275 | Human | 8714 | Details Get a Quote |
| ABCC3 Knockout HCT 116 Cell Line | EDJ-KQ30276 | Human | 8714 | Details Get a Quote |
| ABCC3 Knockout HeLa Cell Line | EDJ-KQ30277 | Human | 8714 | Details Get a Quote |
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