The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SLC22A12  -  solute carrier family 22 (organic...

Homo sapiens

Synonyms: OAT4L, OATL4, Organic anion transporter 4-like protein, RST, Renal-specific transporter, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SLC22A12

  • CONCLUSION: SLC22A12 is a major gene for hypouricemia but not hyperuricemia in Japanese [1].
  • Recent identification of the urate transporter in the kidney (URAT1, encoded by SLC22A12) led to the molecular elucidation of idiopathic renal hypouricemia, which is a predisposition toward exercise-induce acute renal failure [2].
  • Among 96 persons, limb-lead RST deviations occurred in all 48 with pericarditis, but only 27 with early repolarization [3].
  • In 588 patients with treated and untreated syphilis, the RST results were 91.7% in agreement with the VDRL and RPR results [4].
  • A total of 1,020 serum and plasma specimens were tested using the Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR) card, Reagin Screen (RST) and Fluorescent Treponemal Antibody-Absorption (FTA-ABS) tests [4].

High impact information on SLC22A12

  • Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12 [5].
  • Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution [5].
  • The present case-control study was designed to analyze whether hURAT1 might also be a candidate gene for hyperuricemia with primary reduced renal urate excretion [6].
  • Taken together, the present study indicates the novel role of PDZK1 in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules [7].
  • Evidence that the URAT1 transporter was functional was provided by the finding that uptake of (14)C-urate was significantly inhibited in the presence of probenecid, an organic anion transporter inhibitor [8].

Chemical compound and disease context of SLC22A12

  • Because genetic background is known to affect serum urate levels, we hypothesized that genetic variations in SLC22A12 may predispose humans to hyperuricemia and gout [9].

Biological context of SLC22A12


Anatomical context of SLC22A12


Associations of SLC22A12 with chemical compounds

  • Moreover, benzbromarone inhibited the oxypurinol uptake by URAT1 at concentrations as low as 0.01 microM [10].
  • In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid [11].
  • In earlier studies, when the clamped state was induced with an oral ethanol loading dose, the vagaries of gastric emptying and absorption were associated with a 45 min delay (RST: reliable start time) before collection of dependent measurements could be planned with confidence [15].
  • Exercise and isoproterenol tend to normalize the RST segment elevation [16].
  • The sex hormone testosterone significantly increases promoter activity, suggesting that hormonal regulation of hURAT1 is the root cause of observed differences in urate levels between males and females [17].

Regulatory relationships of SLC22A12

  • BACKGROUND: Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12 [18].

Other interactions of SLC22A12

  • Coimmunoprecipitation studies revealed that the wild-type URAT1, but not its mutant lacking the PDZ-motif, directly interacts with PDZK1 [7].
  • Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1) [19].
  • The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry [19].

Analytical, diagnostic and therapeutic context of SLC22A12

  • Such an interaction requires the PDZ motif of URAT1 in its extreme intracellular C-terminal region and the first, second, and fourth PDZ domains of PDZK1 as identified by yeast two-hybrid assay, in vitro binding assay and surface plasmon resonance analysis (K(D) = 1.97-514 nM) [7].
  • However, FST-based estimates are always better than RST when sample sizes are moderate or small (ns </= 10) and the number of loci scored is low (nl < 20) [20].
  • METHODS: Eighteen untrained males were randomly assigned to either a resistance-training [RST (N = 9)] or control group [CON (N = 9)] [21].
  • Restriction enzyme analysis with HphI was useful to screen the IVS2+1G>A mutation in hURAT1 gene [22].
  • (1) extraction by Dormia basket, (2) cystoscopic lithotrity and (3) electronic lithotripsy by Russian-made "URAT 1". Safety and economic advantages to the patients have been discussed [23].


  1. A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. Iwai, N., Mino, Y., Hosoyamada, M., Tago, N., Kokubo, Y., Endou, H. Kidney Int. (2004) [Pubmed]
  2. Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese. Takahashi, T., Tsuchida, S., Oyamada, T., Ohno, T., Miyashita, M., Saito, S., Komatsu, K., Takashina, K., Takada, G. Pediatr. Nephrol. (2005) [Pubmed]
  3. Differential characteristics of the electrocardiogram in early repolarization and acute pericarditis. Spodick, D.H. N. Engl. J. Med. (1976) [Pubmed]
  4. Evaluation of reagin screen, a new serological test for syphilis. Dyckman, J.D., Wende, R.D., Gantenbein, D., Williams, R.P. J. Clin. Microbiol. (1976) [Pubmed]
  5. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Enomoto, A., Kimura, H., Chairoungdua, A., Shigeta, Y., Jutabha, P., Cha, S.H., 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. Nature (2002) [Pubmed]
  6. Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population. Graessler, J., Graessler, A., Unger, S., Kopprasch, S., Tausche, A.K., Kuhlisch, E., Schroeder, H.E. Arthritis Rheum. (2006) [Pubmed]
  7. The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. Anzai, N., Miyazaki, H., Noshiro, R., Khamdang, S., Chairoungdua, A., Shin, H.J., Enomoto, A., Sakamoto, S., Hirata, T., Tomita, K., Kanai, Y., Endou, H. J. Biol. Chem. (2004) [Pubmed]
  8. Human vascular smooth muscle cells express a urate transporter. Price, K.L., Sautin, Y.Y., Long, D.A., Zhang, L., Miyazaki, H., Mu, W., Endou, H., Johnson, R.J. J. Am. Soc. Nephrol. (2006) [Pubmed]
  9. Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese. Shima, Y., Teruya, K., Ohta, H. Life Sci. (2006) [Pubmed]
  10. Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Iwanaga, T., Kobayashi, D., Hirayama, M., Maeda, T., Tamai, I. Drug Metab. Dispos. (2005) [Pubmed]
  11. Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. Ichida, K., Hosoyamada, M., Hisatome, I., Enomoto, A., Hikita, M., Endou, H., Hosoya, T. J. Am. Soc. Nephrol. (2004) [Pubmed]
  12. Function and localization of urate transporter 1 in mouse kidney. Hosoyamada, M., Ichida, K., Enomoto, A., Hosoya, T., Endou, H. J. Am. Soc. Nephrol. (2004) [Pubmed]
  13. Gout in 2006 - the perfect storm. Terkeltaub, R. Bulletin (Hospital for Joint Diseases (New York, N.Y.)) (2006) [Pubmed]
  14. Generation of mouse anti-human urate anion exchanger antibody by genetic immunization and its identification. Xu, G.S., Wu, D., Chen, X.M., Shi, S.Z., Hong, Q., Zhang, P., Lu, Y. Chin. Med. J. (2005) [Pubmed]
  15. A physiologically-based pharmacokinetic (PBPK) model for alcohol facilitates rapid BrAC clamping. Ramchandani, V.A., Bolane, J., Li, T.K., O'Connor, S. Alcohol. Clin. Exp. Res. (1999) [Pubmed]
  16. The early repolarization syndrome. Eastaugh, J.A. The Journal of emergency medicine. (1989) [Pubmed]
  17. Molecular cloning and characterization of a human urate transporter (hURAT1) gene promoter. Li, T., Walsh, J.R., Ghishan, F.K., Bai, L. Biochim. Biophys. Acta (2004) [Pubmed]
  18. Analysis of mutations in the urate transporter 1 (URAT1) gene of Japanese patients with hypouricemia in northern Japan and review of the literature. Komatsuda, A., Iwamoto, K., Wakui, H., Sawada, K., Yamaguchi, A. Renal failure. (2006) [Pubmed]
  19. Development of High-specificity Antibodies against Renal Urate Transporters Using Genetic Immunization. Xu, G., Chen, X., Wu, D., Shi, S., Wang, J., Ding, R., Hong, Q., Feng, Z., Lin, S., Lu, Y. J. Biochem. Mol. Biol. (2006) [Pubmed]
  20. A comparison of two indirect methods for estimating average levels of gene flow using microsatellite data. Gaggiotti, O.E., Lange, O., Rassmann, K., Gliddon, C. Mol. Ecol. (1999) [Pubmed]
  21. Effects of sequential bouts of resistance exercise on androgen receptor expression. Willoughby, D.S., Taylor, L. Medicine and science in sports and exercise. (2004) [Pubmed]
  22. A case of renal hypouricemia caused by urate transporter 1 gene mutations. Inazu, T. Clin. Nephrol. (2006) [Pubmed]
  23. Endoscopic removal of bladder stones in adults. Bapat, S.S. British journal of urology. (1977) [Pubmed]
WikiGenes - Universities