{"id":964,"date":"2016-12-22T23:25:45","date_gmt":"2016-12-22T23:25:45","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=964"},"modified":"2026-02-24T21:12:36","modified_gmt":"2026-02-24T21:12:36","slug":"single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/","title":{"rendered":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri)"},"content":{"rendered":"<p>The genetic code is degenerate. Eighteen of the twenty core amino acids are each encoded by multiple, so-called synonymous codons. The Neutral Theory of Molecular Evolution suggests that synonymous codons will be unaffected by the selective evolutionary pressure and that synonymous mutations will be inconsequential to protein quality. However, recent reports refute this prediction. A new study uncovers the mechanism(s) underlying the origin of Hemophilia B in patients harboring a single synonymous mutation in the F9 gene encoding blood coagulation factor IX. The key novel finding from this study is that a single synonymous mutation results in clinical consequences that lead to a disease via multiple mechanisms that act in concert. (<a href=\"http:\/\/jmg.bmj.com\/content\/early\/2016\/12\/22\/jmedgenet-2016-104072\">http:\/\/jmg.bmj.com\/content\/early\/2016\/12\/22\/jmedgenet-2016-104072<\/a> )<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072.png\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-965\" src=\"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072-300x169.png\" alt=\"figure-5_proof_-jmedgenet-2016-104072\" width=\"300\" height=\"169\" srcset=\"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072-300x169.png 300w, https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072-768x432.png 768w, https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072-1024x576.png 1024w, https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072.png 1280w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The genetic code is degenerate. Eighteen of the twenty core amino acids are each encoded by multiple, so-called synonymous codons. The Neutral Theory of Molecular Evolution suggests that synonymous codons will be unaffected by the selective evolutionary pressure and that synonymous mutations will be inconsequential to protein quality. However, recent reports refute this prediction. A [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/\">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-964","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - 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\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"The genetic code is degenerate. Eighteen of the twenty core amino acids are each encoded by multiple, so-called synonymous codons. The Neutral Theory of Molecular Evolution suggests that synonymous codons will be unaffected by the selective evolutionary pressure and that synonymous mutations will be inconsequential to protein quality. However, recent reports refute this prediction. A [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2016-12-22T23:25:45+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-24T21:12:36+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1280\" \/>\n\t<meta property=\"og:image:height\" content=\"720\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"hqqu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@HuiQiQu\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"hqqu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri)\",\"datePublished\":\"2016-12-22T23:25:45+00:00\",\"dateModified\":\"2026-02-24T21:12:36+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/\"},\"wordCount\":138,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2016\\\/12\\\/Figure-5_Proof_-jmedgenet-2016-104072-300x169.png\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/12\\\/22\\\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\\\/\",\"name\":\"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - 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His research applies human genetics and multi-omics to complex and pediatric diseases, including GWAS, polygenic risk scores (PRS), single-cell transcriptomics, and integrative genomics to support precision medicine and clinical translation.\",\"sameAs\":[\"https:\\\/\\\/x.com\\\/HuiQiQu\"],\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/author\\\/hqiqu\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - JMG Contact blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/","og_locale":"en_US","og_type":"article","og_title":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - JMG Contact blog","og_description":"The genetic code is degenerate. 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A [...]Read More...","og_url":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/","og_site_name":"JMG Contact blog","article_published_time":"2016-12-22T23:25:45+00:00","article_modified_time":"2026-02-24T21:12:36+00:00","og_image":[{"width":1280,"height":720,"url":"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072.png","type":"image\/png"}],"author":"hqqu","twitter_card":"summary_large_image","twitter_creator":"@HuiQiQu","twitter_misc":{"Written by":"hqqu","Est. reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/#article","isPartOf":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/"},"author":{"name":"hqqu","@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/person\/be0250f8d5b52412c3e7c222dabd591b"},"headline":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri)","datePublished":"2016-12-22T23:25:45+00:00","dateModified":"2026-02-24T21:12:36+00:00","mainEntityOfPage":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/"},"wordCount":138,"commentCount":0,"publisher":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#organization"},"image":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/#primaryimage"},"thumbnailUrl":"https:\/\/blogs.bmj.com\/jmg\/files\/2016\/12\/Figure-5_Proof_-jmedgenet-2016-104072-300x169.png","inLanguage":"en-US","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/#respond"]}]},{"@type":"WebPage","@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/","url":"https:\/\/blogs.bmj.com\/jmg\/2016\/12\/22\/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b\/","name":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri) - 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