SLC22A12: Urate Transporter 1 (URAT1) and Its Role in Renal Urate Handling
A comprehensive biomedical overview of SLC22A12, the gene encoding URAT1, its expression, mutations, and clinical significance in urate homeostasis and related disorders.
Gene Information Card
| Symbol | SLC22A12 |
|---|---|
| Full Name | solute carrier family 22 member 12 |
| Gene Type | protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 116085 ncbi.nlm.nih.gov/gene/116085 |
| Ensembl ID | ENSG00000197891 |
| UniProt ID | Q96S37 |
| OMIM ID | 607096 |
| HGNC ID | 17989 |
| Aliases | URAT1, RST, OAT4L |
Description
SLC22A12 encodes the urate transporter 1 (URAT1), a member of the organic anion transporter family. URAT1 is primarily expressed in the apical membrane of renal proximal tubule cells and mediates the reabsorption of urate from the glomerular filtrate. It plays a critical role in maintaining serum urate levels. Loss-of-function mutations in SLC22A12 cause renal hypouricemia type 1 (RHUC1), characterized by low serum urate and increased urinary urate excretion. The gene is also implicated in susceptibility to gout and response to urate-lowering therapies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Renal hypouricemia type 1 (RHUC1) | Loss-of-function mutations in SLC22A12 impair urate reabsorption, leading to excessive urate excretion and low serum urate levels. | OMIM 607096; multiple case reports and functional studies. |
| Gout | Common variants in SLC22A12 (e.g., rs3825016) are associated with altered urate transport and increased risk of hyperuricemia/gout. | Genome-wide association studies (GWAS) and meta-analyses. |
| Exercise-induced acute kidney injury | In RHUC1 patients, strenuous exercise can precipitate acute kidney injury due to increased urate excretion and oxidative stress. | Case reports and clinical studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (nTPM ~ 200) | Predominant expression in renal proximal tubules. |
| Liver | Low (nTPM ~ 5) | Minimal expression. |
| Small intestine | Low (nTPM ~ 3) | Low expression. |
| Other tissues | Not detected | No significant expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HK-2 (renal proximal tubular cells) | High | Endogenous expression; used for functional studies. |
| HEK293 (embryonic kidney) | Low | Often used for heterologous expression after transfection. |
| Caco-2 (intestinal) | Low | Minimal endogenous expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Trp258* (c.774G>A) | Nonsense | Rare (found in RHUC1 families) | Truncated protein; loss of function. |
| p.Arg90His (c.269G>A) | Missense | Rare (found in RHUC1) | Impaired urate transport activity. |
| p.Thr467Met (c.1400C>T) | Missense | Rare (found in RHUC1) | Reduced cell surface expression and transport. |
| rs3825016 (intronic) | SNP | Common (minor allele frequency ~0.2) | Associated with altered urate levels and gout risk. |
Mutation functional classification
Loss of Function (LOF)
Most SLC22A12 mutations are loss-of-function, reducing or abolishing urate transport activity, leading to renal hypouricemia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SLC22A12.
Dominant Negative (DN)
No evidence for dominant-negative effects; the disease is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • urate transmembrane transporter activity | • organic anion transmembrane transporter activity |
| • plasma membrane | • apical plasma membrane |
| • urate transport | • organic anion transport |
Pathways
• Urate homeostasis
• Organic anion transport
• Renal tubular transport
Protein Summary
URAT1 is a 553-amino acid protein with 12 transmembrane domains. It functions as an organic anion exchanger, coupling the uptake of urate to the efflux of other anions (e.g., lactate, nicotinate). It is the primary target of uricosuric drugs (e.g., benzbromarone, probenecid) and is inhibited by these agents to increase urate excretion. URAT1 also interacts with other transporters such as PDZK1 and NHERF1 for proper membrane localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC22A12 Knockout HEK293 Cell Line | EDJ-KQ7545 | Human | 116085 | Details Get a Quote |
| SLC22A12 Knockout HeLa Cell Line | EDJ-KQ57968 | Human | 116085 | Details Get a Quote |
| SLC22A12 Knockout A-549 Cell Line | EDJ-KQ66458 | Human | 116085 | Details Get a Quote |
| SLC22A12 Knockout HCT 116 Cell Line | EDJ-KQ74879 | Human | 116085 | Details Get a Quote |
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