SLC22A12

SLC22A12 is a human gene that encodes URAT1, a high-affinity transporter for uric acid in the kidney. It belongs to the solute carrier 22 (SLC22) family of organic anion transporters. The protein is predominantly expressed in the proximal tubule of the kidney, where it participates in reabsorbing urate from the filtrate back into the bloodstream, contributing to the regulation of systemic uric acid levels.

Function and mechanism: URAT1 mediates the reabsorption of uric acid from urine in the renal proximal tubule. It acts as an exchanger for urate and other monovalent anions, influencing the amount of uric acid returned to the circulation. Through its activity, URAT1 is a key determinant of serum urate homeostasis and interacts functionally with other renal urate transporters.

Clinical significance: Genetic variation in SLC22A12 can affect transporter function and urate handling. Loss-of-function mutations are associated with renal hypouricemia type 1, a condition characterized by low serum uric acid and increased urinary urate excretion. More common variants influence individual differences in serum urate levels and gout risk. Because URAT1 reabsorbs urate, it is a pharmacological target for lowering serum uric acid; URAT1 inhibitors such as lesinurad have been developed for treatment of hyperuricemia in gout.

Nomenclature and context: SLC22A12 is commonly referred to by the protein name URAT1. It is one of several renal urate transporters in the SLC22 family, and ongoing research explores its regulation, interactions with other transporters, and implications for urate-related disorders.