{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:10:14Z","timestamp":1791418214464,"version":"4.3.3"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81202314"],"award-info":[{"award-number":["81202314"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873594"],"award-info":[{"award-number":["81873594"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Focal segmental glomerulosclerosis (FSGS, OMIM\u00ae#603\u2009965) is an overriding cause that leads to end\u2010stage renal disease (ESRD). As a member of TRP superfamily, mutations of\n                      <jats:italic>TRPC6<\/jats:italic>\n                      gene are closely linked to FSGS. By now, 20 missense mutations have been reported, among them, nine gain\u2010of\u2010function (GOF), and five loss\u2010of\u2010function (LOF) mutations have been recognized according to the effect on TRPC6 channel activity. Systematic investigations of functional mutations will provide valuable evidences for understanding the pathophysiology of TRPC6 involved in FSGS. The aim of this study is to investigate the pathogenicity of a novel TRPC6 mutation p.Q134P in FSGS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>High\u2010throughput sequencing was performed to analyse 436 genes which are associated with hereditary kidney diseases in a Chinese pedigree. Then we constructed TRPC6 expression plasmids of wide type and variant. Immunofluorescence, cell\u2010surface biotinylation assays and electrophysiology were used to analyse the localization, cell surface expression, and calcium transport activity of TRPC6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel variant c.401A&gt;C (p.Q134P) in exon 2 of\n                      <jats:italic>TRPC6<\/jats:italic>\n                      gene was found. There was no significant difference between the expression levels of p.Q134P mutant and WT TRPC6 protein in the whole cell lysate and cell\u2010surface fraction. Q134P mutant\u2010bearing TRPC6 elicited much higher Ca\n                      <jats:sup>+<\/jats:sup>\n                      current amplitude than WT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We identified a novel GOF mutation p.Q134P of\n                      <jats:italic>TRPC6<\/jats:italic>\n                      which contributed to late\u2010onset FSGS. Our study expands the mutational spectrum of\n                      <jats:italic>TRPC6<\/jats:italic>\n                      associated with FSGS and furtherly supports the hypothesis of calcium dose\u2013response dependency that a moderate increased calcium influx elicited a mild FSGS phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.13963","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T07:12:40Z","timestamp":1628838760000},"page":"1018-1025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel gain\u2010of\u2010function mutation of\n                    <scp>\n                      <i>TRPC6<\/i>\n                      Q134P\n                    <\/scp>\n                    contributes to late onset focal segmental glomerulosclerosis in a Chinese pedigree"],"prefix":"10.1111","volume":"26","author":[{"given":"Zhiying","family":"Liu","sequence":"first","affiliation":[{"name":"Medical Research Center The Affiliated Hospital of Qingdao University Qingdao China"},{"name":"Department of Nephrology The Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Physiology Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Research Center The Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leping","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical Research Center The Affiliated Hospital of Qingdao University Qingdao 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