{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:12:38Z","timestamp":1781143958463,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-14-00088"],"award-info":[{"award-number":["22-14-00088"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We identified a single nucleotide variation (SNV) (c.1264A &gt; G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation. This missense mutation leads to a p.Lys422Glu (K422E) substitution in the Kv7.1 protein that has never been mentioned before. We inserted this substitution in an expression plasmid containing Kv7.1 cDNA and studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1, using the whole-cell configuration of the patch-clamp technique. Expression of the mutant Kv7.1 channel in both homo- and heterozygous conditions in the presence of auxiliary subunit KCNE1 results in a significant decrease in tail current densities compared to the expression of wild-type (WT) Kv7.1 and KCNE1. This study also indicates that K422E point mutation causes a dominant negative effect. The mutation was not associated with a trafficking defect; the mutant channel protein was confirmed to localize at the cell membrane. This mutation disrupts the poly-Lys strip in the proximal part of the highly conserved cytoplasmic A\u2013B linker of Kv7.1 that was not shown before to be crucial for channel functioning.<\/jats:p>","DOI":"10.3390\/ijms23147953","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T08:28:25Z","timestamp":1658219305000},"page":"7953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome"],"prefix":"10.3390","volume":"23","author":[{"given":"Maria","family":"Karlova","sequence":"first","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis V.","family":"Abramochkin","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia B.","family":"Pustovit","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Nesterova","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, 620049 Ekaterinburg, Russia"},{"name":"Institute of Natural Sciences and Mathematics, Ural Federal University, 620075 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Novoseletsky","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Biology Department, Shenzhen MSU-BIT University, Shenzhen 517182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gildas","family":"Loussouarn","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CNRS, INSERM, l\u2019institut du Thorax, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Zaklyazminskaya","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-232X","authenticated-orcid":false,"given":"Olga S.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Biology Department, Shenzhen MSU-BIT University, Shenzhen 517182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s12551-018-0442-3","article-title":"Role of ion channels in heart failure and channelopathies","volume":"10","author":"Rahm","year":"2018","journal-title":"Biophys. 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