ABCC4: ATP Binding Cassette Subfamily C Member 4
Multidrug Resistance-Associated Protein 4 (MRP4) - Transporter and Drug Resistance Gene
Gene Information Card
| Symbol | ABCC4 |
|---|---|
| Full Name | ATP Binding Cassette Subfamily C Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q32.1 |
| NCBI Gene ID | 10257 ncbi.nlm.nih.gov/gene/10257 |
| Ensembl ID | ENSG00000125257 |
| UniProt ID | O15439 |
| OMIM ID | 605250 |
| HGNC ID | 55 |
| Aliases | MRP4, MOAT-B, MOATB, EST170205 |
Description
ABCC4 (ATP Binding Cassette Subfamily C Member 4) encodes multidrug resistance-associated protein 4 (MRP4), an ATP-binding cassette (ABC) transporter that mediates the efflux of organic anions, nucleoside analogs, and chemotherapeutic drugs. It plays a critical role in drug disposition, detoxification, and resistance to anticancer agents. ABCC4 is expressed in various tissues including kidney, liver, intestine, and blood-brain barrier.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary hearing loss | ABCC4 variants may affect inner ear drug transport; limited evidence | ClinVar |
| Drug-induced liver injury | ABCC4 polymorphisms alter bile acid and drug transport, predisposing to cholestasis | NCBI Gene, ClinVar |
| Cancer (multidrug resistance) | Overexpression of MRP4 effluxes chemotherapeutics (e.g., methotrexate, nucleoside analogs) reducing intracellular drug concentration | COSMIC, NCBI Gene |
| Gout | ABCC4 transports urate; variants associated with altered urate excretion and gout risk | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 28.5 | High |
| Liver | 15.2 | Medium |
| Small intestine | 12.8 | Medium |
| Colon | 9.1 | Medium |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.7 | High expression in transfected cells |
| HepG2 | 12.3 | Endogenous expression |
| Caco-2 | 9.8 | Intestinal epithelial model |
| MDCKII | 7.5 | Used for transport studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2269G>A (p.Gly757Arg) | Missense | 0.01% | Reduced transport activity; associated with drug resistance |
| c.3347G>A (p.Arg1116His) | Missense | 0.02% | Altered substrate specificity |
| c.912C>T (p.Ser304=) | Synonymous | 0.05% | No functional effect; used as marker |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly757Arg) impair ATPase activity and substrate efflux, reducing drug resistance capacity.
Gain of Function (GOF)
Not well characterized; some variants may increase transport efficiency but evidence is limited.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported for ABCC4.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATPase activity coupled to transmembrane movement of substances |
| • xenobiotic transmembrane transporter activity | • organic anion transmembrane transporter activity |
| • nucleoside transmembrane transporter activity | • plasma membrane |
| • basolateral plasma membrane | • response to drug |
| • xenobiotic detoxification by transmembrane export |
Pathways
• ABC transporters
• Drug metabolism - other enzymes
• Bile secretion
• Transport of organic anions
• Methotrexate resistance
Protein Summary
MRP4 (ABCC4) is a 1325-amino acid multidrug resistance-associated protein localized to the plasma membrane. It functions as an ATP-dependent efflux pump for organic anions, cyclic nucleotides, bile acids, and conjugated drugs. MRP4 is implicated in chemoresistance, particularly to nucleoside analogs (e.g., 6-mercaptopurine, methotrexate) and antiviral drugs. Its expression in kidney and liver contributes to systemic drug clearance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCC4 Knockout HEK293 Cell Line | EDJ-KQ1092 | Human | 10257 | Details Get a Quote |
| ABCC4 Knockout A-549 Cell Line | EDJ-KQ20257 | Human | 10257 | Details Get a Quote |
| ABCC4 Knockout HCT 116 Cell Line | EDJ-KQ20258 | Human | 10257 | Details Get a Quote |
| ABCC4 Knockout HeLa Cell Line | EDJ-KQ20259 | Human | 10257 | Details Get a Quote |
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