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The mechanisms underlying these heterogeneous phenotypes remain poorly understood, although post\u2010translational modifications, including phosphorylation, are postulated as regulators of lamin function. We catalogued all known lamin A\/C human mutations and their associated phenotypes, and systematically examined the putative role of phosphorylation in laminopathies. In silico prediction of specific\n                    <jats:italic>LMNA<\/jats:italic>\n                    mutant\u2010driven changes to lamin A phosphorylation and protein structure was performed using machine learning methods. Some of the predictions we generated were validated via assessment of ectopically expressed wild\u2010type and mutant\n                    <jats:italic>LMNA<\/jats:italic>\n                    . Our findings indicate phenotype\u2010 and mutant\u2010specific alterations in lamin phosphorylation, and that some changes in phosphorylation may occur independently of predicted changes in lamin protein structure. Therefore, therapeutic targeting of phosphorylation in the context of laminopathies will likely require mutant\u2010 and kinase\u2010specific approaches.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000500r","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T03:26:40Z","timestamp":1589599600000},"page":"9051-9073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genotype\u2010phenotype analysis of\n                    <i>LMNA<\/i>\n                    \u2010related diseases predicts phenotype\u2010selective alterations in lamin phosphorylation"],"prefix":"10.1096","volume":"34","author":[{"given":"Eric W.","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI USA"},{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham F.","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI USA"},{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI USA"},{"name":"Center for Advanced Biotechnology and Medicine Rutgers University Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey I.","family":"Nesvizhskii","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI USA"},{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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