Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia

Renal hypouricemia is a rare genetic disorder. Hypouricemia can present as renal stones or exercise-induced acute renal failure, but most cases are asymptomatic. Our previous study showed that two recessive variants of SLC22A12 (p.Trp258*, pArg90His) were identified in 90% of the hypouricemia patients from two independent cohorts: the Korean genome and epidemiology study (KoGES) and the Korean Cancer Prevention Study (KCPS-II). In this work, we investigate the genetic causes of hypouricemia in the rest of the 10% of unsolved cases. We found a novel non-synonymous mutation of (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in (p.Met155Val in hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the protein expression level. Our results will shed light on a better understanding of -mediated uric acid transport and the development of a uric acid-lowering agent.