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Previous studies have identified several bi\u2010allelic mutations of\n                    <jats:italic>KCNJ16<\/jats:italic>\n                    in humans, causing severe hypokalemia, renal salt wasting, and disturbed acid\u2013base homeostasis. Here, we identified a novel homozygous variant of\n                    <jats:italic>KCNJ16<\/jats:italic>\n                    ,\n                    <jats:italic>I26T<\/jats:italic>\n                    , in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration. Subsequently, we generated the rat model with\n                    <jats:italic>I26T<\/jats:italic>\n                    mutation using Dahl salt\u2010sensitive rat (I26T rat) to characterize this variant. The male mutant rats displayed similar blood pressure and electrolyte homeostasis under baseline and with a high salt (4% NaCl) challenge. Blood pH, HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and renal damage also remained similar between WT and I26T rats after high salt challenge. Additionally, single\u2010channel patch clamp analysis revealed similar channel activity in CHO cells overexpressed with WT and\n                    <jats:italic>I26T<\/jats:italic>\n                    mutant K\n                    <jats:sub>ir<\/jats:sub>\n                    4.1\/5.1 channels. In summary, this study reported a novel variant in\n                    <jats:italic>KCNJ16<\/jats:italic>\n                    , namely\n                    <jats:italic>I26T<\/jats:italic>\n                    , which is likely a benign variant and not associated with pathologic phenotype in either human or Dahl salt\u2010sensitive rats, indicating that the type\/location of variant should be considered when diagnosing and treating patients with\n                    <jats:italic>KCNJ16<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70083","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T21:39:39Z","timestamp":1729114779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of a novel variant in\n                    <scp>\n                      <i>KCNJ16<\/i>\n                    <\/scp>\n                    , encoding K\n                    <sub>ir<\/sub>\n                    5.1 channel"],"prefix":"10.14814","volume":"12","author":[{"given":"Biyang","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Bohovyk","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameneh","family":"Ahrari","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron M.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Sency","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children  Middlefield Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baozhong","family":"Xin","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children  Middlefield Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children  Middlefield Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-8356","authenticated-orcid":false,"given":"Alexander","family":"Staruschenko","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa Florida USA"},{"name":"Hypertension and Kidney Research Center, University of South Florida  Tampa Florida USA"},{"name":"James A. Haley Veterans' Hospital  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2238"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104887"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201527"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-167262"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15779"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.14772"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-014-8295-9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20190876"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.121.000464"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2020.02.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2019.03.009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-019-0236-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92331"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041285"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020111587"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901749106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2012.tb00434.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.056804"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2020.03158"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00883-0"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15510"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00059.2023"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70083","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.70083","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:01:22Z","timestamp":1789563682000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":23,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.14814\/phy2.70083"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70083","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70083"}}