{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T22:45:54Z","timestamp":1787352354128,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Koum Family Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100015521","name":"Stanford Maternal and Child Health Research Institute","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100015521","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["project ID 394046635\u2014SFB 1365"],"award-info":[{"award-number":["project ID 394046635\u2014SFB 1365"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["R01 (DK117865)"],"award-info":[{"award-number":["R01 (DK117865)"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["NIH U2C\/TL1 LAUNCH program (NIDDK TL1 DK139565)"],"award-info":[{"award-number":["NIH U2C\/TL1 LAUNCH program (NIDDK TL1 DK139565)"]}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["NIDDK 1K99DK131361"],"award-info":[{"award-number":["NIDDK 1K99DK131361"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"crossref","award":["American Society of Nephrology Ben J. Lipps Research Fellowship Program"],"award-info":[{"award-number":["American Society of Nephrology Ben J. Lipps Research Fellowship Program"]}],"id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:p>\n                    Mutations in the\n                    <jats:italic>CLCNKB<\/jats:italic>\n                    gene (1p36), encoding the basolateral chloride channel ClC-Kb, cause type 3 Bartter syndrome. We identified a family with a mixed Bartter\/Gitelman phenotype and early-onset kidney failure and by employing a candidate gene approach, identified what we believe is a novel homozygous mutation (\n                    <jats:italic>CLCNKB<\/jats:italic>\n                    c.499G&gt;T [p.Gly167Cys]) in exon 6 of\n                    <jats:italic>CLCNKB<\/jats:italic>\n                    in the index patient. We then validated these results with Sanger and whole-exome sequencing. Compared with wild-type ClC-Kb, the Gly167Cys mutant conducted less current and exhibited impaired complex N-linked glycosylation in vitro. We demonstrated that loss of Gly-167, rather than gain of a mutant Cys, impairs complex glycosylation, but that surface expression remains intact. Moreover, Asn-364 was necessary for channel function and complex glycosylation. Morphologic evaluation of human kidney biopsies revealed typical basolateral localization of mutant Gly167Cys ClC-Kb in cortical distal tubular epithelia. However, we detected attenuated expression of distal sodium transport proteins, changes in abundance of distal tubule segments, and hypokalemia-associated intracellular condensates from the index patient compared with control nephrectomy specimens. The present data establish what we believe are novel regulatory mechanisms of ClC-Kb activity and demonstrate nephron remodeling in humans, caused by mutant ClC-Kb, with implications for renal electrolyte handling, blood pressure control, and kidney disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.175998","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T12:00:42Z","timestamp":1728993642000},"source":"Crossref","is-referenced-by-count":7,"title":["ClC-Kb pore mutation disrupts glycosylation and triggers distal tubular remodeling"],"prefix":"10.1172","volume":"9","author":[{"given":"Yogita","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Lo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-2481","authenticated-orcid":true,"given":"Viktor N.","family":"Tomilin","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotdaji","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Physiology, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Deremo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya V.","family":"Pareek","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuxing","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Liao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Lebedeva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmacy, I.M. 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