Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F19%3AN0000026" target="_blank" >RIV/00023728:_____/19:N0000026 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/19:10403729 RIV/00216208:11320/19:10403729 RIV/00216208:11110/19:10403729

Result on the web

<a href="https://doi.org/10.3390/cells8040363" target="_blank" >https://doi.org/10.3390/cells8040363</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells8040363" target="_blank" >10.3390/cells8040363</a>

Result language

angličtina

Original language name

Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort

Original language description

ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia; recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of ABCG2 on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of ABCG2. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of ABCG2-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30226 - Rheumatology

Project

<a href="/en/project/NV15-26693A" target="_blank" >NV15-26693A: Function study of allelic variants of urate transporters in primary hyperuricemia and gout</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

2073-4409

Volume of the periodical

8

Issue of the periodical within the volume

4

Country of publishing house

CH - SWITZERLAND

Number of pages

1

Pages from-to

Art.Nr.363

UT code for WoS article

000467304300077

EID of the result in the Scopus database

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