{"id":1774,"date":"2022-10-03T15:01:16","date_gmt":"2022-10-03T15:01:16","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=1774"},"modified":"2026-02-23T00:40:15","modified_gmt":"2026-02-23T00:40:15","slug":"identifying-the-molecular-drivers-of-als-implicated-missense-mutations","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2022\/10\/03\/identifying-the-molecular-drivers-of-als-implicated-missense-mutations\/","title":{"rendered":"Identifying the molecular drivers of ALS-implicated missense mutations (Contributed by Dr. David Ascher)"},"content":{"rendered":"<p>Genetic mutations have long been identified as contributors to ALS, however, their molecular-consequences have remained elusive. To address this, we analysed the effects of ALS missense mutations in SOD1, FUS and TDP-43 using in silico tools. FUS and TDP-43 mutations affected disordered regions associated with phase separation and aggregation, while SOD1 mutations destabilized the homodimer, which is linked to toxic trimer formation. Furthermore, we compiled 1,343 clinical missense mutations spanning 111 genes, into the most comprehensive resource of mutations clinically associated with ALS. This database, along with our analysis pipeline, offers clinicians an insightful resource to aid efficient ALS diagnosis. (<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2022\/09\/30\/jmg-2022-108798\">https:\/\/jmg.bmj.com\/content\/early\/2022\/09\/30\/jmg-2022-108798<\/a>)<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Genetic mutations have long been identified as contributors to ALS, however, their molecular-consequences have remained elusive. To address this, we analysed the effects of ALS missense mutations in SOD1, FUS and TDP-43 using in silico tools. FUS and TDP-43 mutations affected disordered regions associated with phase separation and aggregation, while SOD1 mutations destabilized the homodimer, [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2022\/10\/03\/identifying-the-molecular-drivers-of-als-implicated-missense-mutations\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":123,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1774","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Identifying the molecular drivers of ALS-implicated missense mutations (Contributed by Dr. David Ascher) - JMG Contact blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/jmg\/2022\/10\/03\/identifying-the-molecular-drivers-of-als-implicated-missense-mutations\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Identifying the molecular drivers of ALS-implicated missense mutations (Contributed by Dr. David Ascher) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"Genetic mutations have long been identified as contributors to ALS, however, their molecular-consequences have remained elusive. To address this, we analysed the effects of ALS missense mutations in SOD1, FUS and TDP-43 using in silico tools. 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