{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:25:16Z","timestamp":1780986316431,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T00:00:00Z","timestamp":1724457600000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant movement disorders. Among the SCAs associated with impaired ion channel function, SCA19\/22 is caused by pathogenic variants in <jats:italic>KCND3<\/jats:italic>, which encodes the voltage\u2010gated potassium channel Kv4.3. SCA19\/22 is clinically characterized by ataxia, dysarthria and oculomotor dysfunction in combination with other signs and symptoms, including mild cognitive impairment, peripheral neuropathy and pyramidal signs. The known <jats:italic>KCND3<\/jats:italic> pathogenic variants are localized either in the transmembrane segments, the connecting loops, or the C\u2010terminal region of Kv4.3. We have identified a novel pathogenic variant, c.455A&gt;G (p.D152G), localized in the N\u2010terminus of Kv4.3. It is located in the immediate neighbourhood of the T1 domain, which is responsible for multimerization with the \u03b2\u2010subunit KChIP2b and thus for the formation of functional heterooctamers. Electrophysiological studies showed that p.D152G does not affect channel gating, but reduces the ionic current in Kv4.3, even though the variant is not located in the transmembrane domains. Impaired channel trafficking to the plasma membrane may contribute to this effect. In a patient with a clinical picture corresponding to SCA19\/22, p.D152G is the first pathogenic variant in the N\u2010terminus of Kv4.3 to be described to date with an effect on ion channel activity.<\/jats:p>","DOI":"10.1111\/jcmm.70039","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T14:43:11Z","timestamp":1724510591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel <i>KCND3<\/i> variant in the N\u2010terminus impairs the ionic current of Kv4.3 and is associated with <scp>SCA19<\/scp>\/22"],"prefix":"10.1111","volume":"28","author":[{"given":"Marlen Colleen","family":"Reis","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Justus\u2010Liebig\u2010University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mandler","sequence":"additional","affiliation":[{"name":"Institute of Human 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