SLC47A1 Gene - Multidrug and Toxin Extrusion Protein 1 (MATE1)
SLC47A1 encodes MATE1, a key renal and hepatic transporter involved in the excretion of metformin and other organic cations, with implications for drug response and toxicity.
Gene Information Card
| Symbol | SLC47A1 |
|---|---|
| Full Name | solute carrier family 47 member 1 |
| Gene Type | protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 55244 ncbi.nlm.nih.gov/gene/55244 |
| Ensembl ID | ENSG00000142409 |
| UniProt ID | Q96FL8 |
| OMIM ID | 609832 |
| HGNC ID | 25588 |
| Aliases | MATE1, MATE-1, FLJ10857 |
Description
SLC47A1 (solute carrier family 47 member 1) encodes the multidrug and toxin extrusion protein 1 (MATE1), a polyspecific organic cation transporter expressed predominantly in the kidney and liver. MATE1 mediates the efflux of endogenous metabolites and xenobiotics, including many clinically used drugs such as metformin, cimetidine, and cisplatin. It plays a critical role in the final step of renal secretion and hepatic biliary excretion, and its function is essential for the pharmacokinetics and pharmacodynamics of cationic drugs. Genetic variants in SLC47A1 have been associated with altered drug response and risk of drug-induced toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Metformin-associated lactic acidosis | Reduced MATE1 function due to genetic variants may impair metformin excretion, leading to elevated plasma levels and increased risk of lactic acidosis. | ClinVar and pharmacogenetic studies (e.g., rs2289669) have shown associations with metformin response and gastrointestinal intolerance. |
| Cisplatin-induced nephrotoxicity | MATE1 mediates renal secretion of cisplatin; reduced expression or function can lead to increased intracellular accumulation in renal tubular cells, causing nephrotoxicity. | Studies in cell models and clinical cohorts have linked SLC47A1 variants to cisplatin-induced kidney injury. |
| Drug-induced liver injury (DILI) | MATE1 is involved in biliary excretion of drugs; impaired function may contribute to hepatic accumulation of toxic compounds. | Evidence from in vitro studies and case reports suggests a role in DILI, though direct clinical evidence is limited. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (nTPM ~ 200) | Predominant expression in renal proximal tubules |
| Liver | Moderate (nTPM ~ 50) | Expressed in hepatocytes, particularly at the bile canalicular membrane |
| Adrenal gland | Low (nTPM ~ 10) | Minimal expression |
| Small intestine | Low (nTPM ~ 5) | Detected in enterocytes |
| Skeletal muscle | Not detected | No significant expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HK-2 (renal proximal tubular) | High | Model for renal MATE1 function |
| HepG2 (hepatocellular carcinoma) | Moderate | Used for hepatic transport studies |
| Caco-2 (intestinal) | Low | Minimal expression |
| HEK293 (embryonic kidney) | Low | Often used for heterologous expression after transfection |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2289669 (intronic) | SNV | Allele frequency ~0.3 (G allele) | Associated with reduced metformin response and altered glycemic control in type 2 diabetes |
| rs2453580 (intronic) | SNV | Allele frequency ~0.2 | Linked to altered metformin pharmacokinetics |
| c.404C>T (p.Ala135Val) | Missense | Rare (<0.01) | In vitro reduced transport activity for metformin |
| c.1018G>A (p.Val340Ile) | Missense | Rare (<0.01) | Potential impact on substrate specificity; functional data limited |
Mutation functional classification
Loss of Function (LOF)
Variants such as p.Ala135Val have been shown to reduce MATE1-mediated transport of metformin and other cations, leading to decreased renal excretion and increased systemic exposure.
Gain of Function (GOF)
No clear gain-of-function variants have been reported for SLC47A1; most studies focus on loss-of-function or altered expression.
Dominant Negative (DN)
No evidence for dominant-negative effects; MATE1 functions as a monomer, and haploinsufficiency may be relevant in some contexts.
View complete mutation data：
Gene Ontology (GO)
| • xenobiotic transmembrane transporter activity | • organic cation transmembrane transporter activity |
| • antiporter activity | • plasma membrane |
| • integral component of membrane | • response to drug |
| • renal tubular secretion | • bile acid and bile salt transport |
Pathways
• Metformin transport pathway
• Organic cation transport
• Renal clearance of drugs
• Hepatic elimination of xenobiotics
Protein Summary
MATE1 is a 570-amino acid polyspecific transporter with 13 predicted transmembrane domains. It functions as an electroneutral H+/organic cation antiporter, utilizing the inward proton gradient to drive efflux of organic cations across the apical membrane of renal proximal tubule cells and the bile canalicular membrane of hepatocytes. MATE1 interacts with OCT2 (SLC22A2) in the kidney to mediate vectorial transport of cationic drugs. Its substrate spectrum includes metformin, cimetidine, procainamide, and various toxins. Post-translational modifications and oligomerization may affect its activity, and its expression is regulated by nuclear receptors and hormonal factors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC47A1 Knockout HEK293 Cell Line | EDJ-KQ15346 | Human | 55244 | Details Get a Quote |
| SLC47A1 Knockout A-549 Cell Line | EDJ-KQ46075 | Human | 55244 | Details Get a Quote |
| SLC47A1 Knockout HeLa Cell Line | EDJ-KQ44856 | Human | 55244 | Details Get a Quote |
| SLC47A1 Knockout HCT 116 Cell Line | EDJ-KQ73503 | Human | 55244 | Details Get a Quote |
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