{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:49:08Z","timestamp":1791614948555,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III-Subdireccion General de Evaluacion y Fomento de la Investigacion and the European Regional Development Fund \u201cAnother way to build Europe\u201d","award":["PI20\/00652"],"award-info":[{"award-number":["PI20\/00652"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Renal hypouricemia (RHUC) is a rare hereditary disorder caused by loss-of-function mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes, encoding urate transporters URAT1 and GLUT9, respectively, that reabsorb urate in the renal proximal tubule. The characteristics of this disorder are low serum urate levels, high renal fractional excretion of urate, and occasional severe complications such as nephrolithiasis and exercise-induced acute renal failure. In this study, we report two Spanish (Caucasian) siblings and a Pakistani boy with clinical characteristics compatible with RHUC. Whole-exome sequencing (WES) analysis identified two homozygous variants: a novel pathogenic SLC22A12 variant, c.1523G&gt;A; p.(S508N), in the two Caucasian siblings and a previously reported SLC2A9 variant, c.646G&gt;A; p.(G216R), in the Pakistani boy. Our findings suggest that these two mutations cause RHUC through loss of urate reabsorption and extend the SLC22A12 mutation spectrum. In addition, this work further emphasizes the importance of WES analysis in clinical settings.<\/jats:p>","DOI":"10.3390\/genes14091823","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T21:26:32Z","timestamp":1695245192000},"page":"1823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["New SLC22A12 (URAT1) Variant Associated with Renal Hypouricemia Identified by Whole-Exome Sequencing Analysis and Bioinformatics Predictions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2562-2119","authenticated-orcid":false,"given":"Ana","family":"Perdomo-Ram\u00edrez","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ramos-Trujillo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"},{"name":"Departamento de Medicina F\u00edsica y Farmacolog\u00eda, Facultad de Ciencias de la Salud, Secci\u00f3n Medicina, Universidad de La Laguna, 38071 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2468-3267","authenticated-orcid":false,"given":"F\u00e9lix","family":"Claverie-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ymgme.2006.03.015","article-title":"Hereditary renal hypouricemia","volume":"89","author":"Sperling","year":"2006","journal-title":"Mol. 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