{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:57:20Z","timestamp":1790402240952,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["15H05610 (to Y.T.); 16H1808 and 18KK0247 (to T.T.)"],"award-info":[{"award-number":["15H05610 (to Y.T.); 16H1808 and 18KK0247 (to T.T.)"]}]},{"name":"Czech Republic Ministry of Health","award":["AZV 15-26693 A (to B.S.)"],"award-info":[{"award-number":["AZV 15-26693 A (to B.S.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells8040363","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T11:58:21Z","timestamp":1555588701000},"page":"363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7411-0531","authenticated-orcid":false,"given":"Yu","family":"Toyoda","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Man\u010d\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edr","family":"Krylov","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keito","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"Pavelcov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, 128 50 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Bohat\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, 128 50 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pavelka","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, 128 50 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00e9ta","family":"Pavl\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, 121 16 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama 359-8513, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-9320","authenticated-orcid":false,"given":"Tappei","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-1476","authenticated-orcid":false,"given":"Blanka","family":"Stiburkova","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, 128 50 Prague 2, Czech Republic"},{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, 121 08 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(16)00346-9","article-title":"Gout","volume":"388","author":"Dalbeth","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0006-291X(90)91194-W","article-title":"Human urate oxidase gene: Cloning and partial sequence analysis reveal a stop codon within the fifth exon","volume":"171","author":"Yeldandi","year":"1990","journal-title":"Biochem. 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