{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:43:43Z","timestamp":1793357023441,"version":"4.5.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>KCNJ16<\/jats:italic>encodes K<jats:sub>ir<\/jats:sub>5.1 and acts in combination with K<jats:sub>ir<\/jats:sub>4.1, encoded by<jats:italic>KCNJ10<\/jats:italic>, to form an inwardly rectifying K<jats:sup>+<\/jats:sup>channel expressed at the basolateral membrane of epithelial cells in the distal nephron. This K<jats:sub>ir<\/jats:sub>4.1\/K<jats:sub>ir<\/jats:sub>5.1 channel is critical for controlling basolateral membrane potential and K<jats:sup>+<\/jats:sup>recycling, the latter coupled to Na-K-ATPase activity, which determines renal Na<jats:sup>+<\/jats:sup>handling. Previous work has shown that<jats:italic>Kcnj16<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice and SS<jats:sup><jats:italic>Kcnj16<\/jats:italic>\u2212\/\u2212<\/jats:sup>rats demonstrate hypokalemic, hyperchloremic metabolic acidosis. Here, we present the first report of a patient identified to have biallelic loss-of-function variants in<jats:italic>KCNJ16<\/jats:italic>by whole exome sequencing who presented with chronic metabolic acidosis with exacerbations triggered by minor infections.<\/jats:p>","DOI":"10.1038\/s41431-021-00883-0","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T02:02:43Z","timestamp":1618192963000},"page":"1566-1569","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biallelic loss-of-function variants in KCNJ16 presenting with hypokalemic metabolic acidosis"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6174-4677","authenticated-orcid":false,"given":"Bryn D.","family":"Webb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Hotchkiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Prasun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-5027","authenticated-orcid":false,"given":"Bruce D.","family":"Gelb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-1748","authenticated-orcid":false,"given":"Lisa","family":"Satlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"883_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00021.2009","volume":"90","author":"H Hibino","year":"2010","unstructured":"Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010;90:291\u2013366.","journal-title":"Physiol Rev"},{"key":"883_CR2","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1042\/CS20190876","volume":"133","author":"AD Manis","year":"2019","unstructured":"Manis AD, Palygin O, Khedr S, Levchenko V, Hodges MR, Staruschenko A. Relationship between the renin-angiotensin-aldosterone system and renal Kir5.1 channels. Clin Sci. 2019;133:2449\u201361.","journal-title":"Clin Sci"},{"key":"883_CR3","doi-asserted-by":"publisher","first-page":"10361","DOI":"10.1073\/pnas.1101400108","volume":"108","author":"M Paulais","year":"2011","unstructured":"Paulais M, Bloch-Faure M, Picard N, Jacques T, Ramakrishnan SK, Keck M, et al. Renal phenotype in mice lacking the Kir5.1 (Kcnj16) K+ channel subunit contrasts with that observed in SeSAME\/EAST syndrome. 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