SLC22A12 explained

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 SLC22A12 gene.^{[1] [2]}

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.^[1]

Clinical significance

Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys.^{[3] [4]} Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia.

Interactions

SLC22A12 has been shown to have a protein-protein interaction with PDZK1.^[5]

Inhibition

Lesinurad, Ruzinurad, Verinurad, Epaminurad, Lingdolinurad, Xininurad, Puliginurad and dotinurad are urate transporter inhibitors that have been approved to treat gout.^{[6] [7]} Lesinurad enhances urate excretion by inhibition the tubular re-absorption. Probenecid also facilitates uric acid secretion.^{[8] [9]}

See also

• Solute carrier family

Further reading

• Hediger MA, Johnson RJ, Miyazaki H, Endou H . Molecular physiology of urate transport. . Physiology . 20 . 2 . 125–33 . 2005 . 15772301 . 10.1152/physiol.00039.2004 .
• 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 . Molecular identification of a renal urate anion exchanger that regulates blood urate levels. . Nature . 417 . 6887 . 447–52 . 2002 . 12024214 . 10.1038/nature742 . 2002Natur.417..447E . 4417844 .
• Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H . PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. . Kidney Int. . 64 . 5 . 1733–45 . 2004 . 14531806 . 10.1046/j.1523-1755.2003.00266.x . free .
• Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T . Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. . J. Am. Soc. Nephrol. . 15 . 1 . 164–73 . 2004 . 14694169 . 10.1097/01.ASN.0000105320.04395.D0 . free .
• Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H . The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. . J. Biol. Chem. . 279 . 44 . 45942–50 . 2004 . 15304510 . 10.1074/jbc.M406724200 . free .
• Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H . A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. . Kidney Int. . 66 . 3 . 935–44 . 2004 . 15327384 . 10.1111/j.1523-1755.2004.00839.x . free .
• Takahashi T, Tsuchida S, Oyamada T, Ohno T, Miyashita M, Saito S, Komatsu K, Takashina K, Takada G . Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese. . Pediatr. Nephrol. . 20 . 5 . 576–8 . 2005 . 15772829 . 10.1007/s00467-005-1830-z . 12711324 .
• Taniguchi A, Urano W, Yamanaka M, Yamanaka H, Hosoyamada M, Endou H, Kamatani N . 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 . 2005 . 16059895 . 10.1002/art.21242 .
• Shima Y, Teruya K, Ohta H . Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese. . Life Sci. . 79 . 23 . 2234–7 . 2006 . 16920156 . 10.1016/j.lfs.2006.07.030 .
• Ohtsuka Y, Zaitsu M, Ichida K, Isomura N, Tsuji K, Sato T, Hamasaki Y . Human uric acid transporter 1 gene analysis in familial renal hypo-uricemia associated with exercise-induced acute renal failure. . . 49 . 2 . 235–7 . 2007 . 17445045 . 10.1111/j.1442-200X.2007.02337.x . 25818777 .

Notes and References

1. Web site: Entrez Gene: SLC22A12 solute carrier family 22 (organic anion/cation transporter), member 12.
2. 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 . Molecular identification of a renal urate anion exchanger that regulates blood urate levels . Nature . 417 . 6887 . 447–52 . May 2002 . 12024214 . 10.1038/nature742 . 2002Natur.417..447E . 4417844 .
3. Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, Schroeder HE . 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 . January 2006 . 16385546 . 10.1002/art.21499 .
4. Wakida N, Tuyen DG, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K . Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia . J. Clin. Endocrinol. Metab. . 90 . 4 . 2169–74 . April 2005 . 15634722 . 10.1210/jc.2004-1111 . free .
5. Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H . PDZK1: I. a major scaffolder in brush borders of proximal tubular cells . Kidney Int. . 64 . 5 . 1733–45 . November 2003 . 14531806 . 10.1046/j.1523-1755.2003.00266.x . free .
6. Web site: FDA approves Zurampic to treat high blood uric acid levels associated with gout . United States Food and Drug Administration . 22 December 2015.
7. Web site: List of Approved Products . .
8. Hsyu PH, Gisclon LG, Hui AC, Giacomini KM . Interactions of organic anions with the organic cation transporter in renal BBMV . The American Journal of Physiology . 254 . 1 Pt 2 . F56–61 . Jan 1988 . 2962517 . 10.1152/ajprenal.1988.254.1.F56.
9. Silverman W, Locovei S, Dahl G . Probenecid, a gout remedy, inhibits pannexin 1 channels . American Journal of Physiology. Cell Physiology . 295 . 3 . C761–7 . September 2008 . 18596212 . 10.1152/ajpcell.00227.2008 . 2544448.