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 patien...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicines 2021-09, Vol.9 (9), p.1172
Main Authors: Yoon, Jaeho, Cachau, Raul, David, Victor A, Thompson, Mary, Jung, Wooram, Jee, Sun-Ha, Daar, Ira O, Winkler, Cheryl A, Cho, Sung-Kweon
Format: Article
Language:English
Subjects:
Binding sites
Cancer
Disease prevention
Epidemiology
Genetic disorders
Genomes
Homeostasis
hypouricemia
Kidneys
Laboratory animals
Minority & ethnic groups
Mutagenesis
Mutation
Nephrolithiasis
Oocytes
Renal failure
SLC2A9
Software
Uric acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9091172