{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:04:45Z","timestamp":1788595485775,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35118089"],"award-info":[{"award-number":["R35118089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calmodulin (CaM) is a ubiquitous intracellular Ca2+ sensing protein that modifies gating of numerous ion channels. CaM has an extraordinarily high level of evolutionary conservation, which led to the fundamental assumption that mutation would be lethal. However, in 2012, complete exome sequencing of infants suffering from recurrent cardiac arrest revealed de novo mutations in the three human CALM genes. The correlation between mutations and pathophysiology suggests defects in CaM-dependent ion channel functions. Here, we review the current state of the field for all reported CaM mutations associated with cardiac arrhythmias, including knowledge of their biochemical and structural characteristics, and progress towards understanding how these mutations affect cardiac ion channel function.<\/jats:p>","DOI":"10.3390\/ijms21041418","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T03:20:03Z","timestamp":1582168803000},"page":"1418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Calmodulin Mutations Associated with Heart Arrhythmia: A Status Report"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-0790","authenticated-orcid":false,"given":"Walter J.","family":"Chazin","sequence":"first","affiliation":[{"name":"Departments of Biochemistry, Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher N.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Vanderbilt Center for Arrhythmia Research and Therapeutics, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.2174\/1874467208666150507105105","article-title":"Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging","volume":"8","author":"Santulli","year":"2015","journal-title":"Curr. Mol. 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