Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12gene.[5][6]
Function
The protein encoded by this gene is a urate transporter and urate-anion exchanger which regulates the level of urate in the blood. This protein is an integral membrane protein primarily found in kidney. Two transcript variants encoding different isoforms have been found for this gene.[5]
Clinical significance
Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys.[7][8] Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia.
Interactions
SLC22A12 has been shown to have a protein-protein interaction with PDZK1.[9]
Inhibition
Lesinurad,Ruzinurad and dotinurad are urate transporter inhibitors that have been approved to treat gout.[10][11] Lesinurad enhances urate excretion by inhibition the tubular re-absorption. Probenecid also facilitates uric acid secretion.[12][13]
^Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (May 2002). "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature. 417 (6887): 447–52. Bibcode:2002Natur.417..447E. doi:10.1038/nature742. PMID12024214. S2CID4417844.
^Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, Schroeder HE (January 2006). "Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population". Arthritis Rheum. 54 (1): 292–300. doi:10.1002/art.21499. PMID16385546.
^Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (January 1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". The American Journal of Physiology. 254 (1 Pt 2): F56–61. doi:10.1152/ajprenal.1988.254.1.F56. PMID2962517.
Hediger MA, Johnson RJ, Miyazaki H, Endou H (2005). "Molecular physiology of urate transport". Physiology. 20 (2): 125–33. doi:10.1152/physiol.00039.2004. PMID15772301.
Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (2002). "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature. 417 (6887): 447–52. Bibcode:2002Natur.417..447E. doi:10.1038/nature742. PMID12024214. S2CID4417844.
Takahashi T, Tsuchida S, Oyamada T, Ohno T, Miyashita M, Saito S, Komatsu K, Takashina K, Takada G (2005). "Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese". Pediatr. Nephrol. 20 (5): 576–8. doi:10.1007/s00467-005-1830-z. PMID15772829. S2CID12711324.
Taniguchi A, Urano W, Yamanaka M, Yamanaka H, Hosoyamada M, Endou H, Kamatani N (2005). "A common mutation in an organic anion transporter gene, SLC22A12, is a suppressing factor for the development of gout". Arthritis Rheum. 52 (8): 2576–7. doi:10.1002/art.21242. PMID16059895.
Shima Y, Teruya K, Ohta H (2006). "Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese". Life Sci. 79 (23): 2234–7. doi:10.1016/j.lfs.2006.07.030. PMID16920156.
