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Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia

Authors
 Jaeho Yoon  ;  Raul Cachau  ;  Victor A David  ;  Mary Thompson  ;  Wooram Jung  ;  Sun-Ha Jee  ;  Ira O Daar  ;  Cheryl A Winkler  ;  Sung-Kweon Cho 
Citation
 BIOMEDICINES, Vol.9(9) : 1172, 2021-09 
Journal Title
BIOMEDICINES
Issue Date
2021-09
Keywords
SLC2A9 ; hypouricemia
Abstract
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 SLC2A9 (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in SLCA9b (p.Met155Val in SLC2A9a) hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using Xenopus oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the SLC2A9 protein expression level. Our results will shed light on a better understanding of SLC2A9-mediated uric acid transport and the development of a uric acid-lowering agent.
Files in This Item:
T202124661.pdf Download
DOI
10.3390/biomedicines9091172
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187500
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