{"id":12785,"date":"2023-03-01T14:31:32","date_gmt":"2023-03-01T13:31:32","guid":{"rendered":"https:\/\/www.humangenetik-umg.de\/?p=12785"},"modified":"2023-03-01T14:31:32","modified_gmt":"2023-03-01T13:31:32","slug":"gene-of-the-month-february-hmgb1","status":"publish","type":"post","link":"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-hmgb1\/","title":{"rendered":"Gene of the Month &#8211; February: HMGB1"},"content":{"rendered":"<p>Specific heterozygous variants in <em>HMGB1<\/em> cause an extremely rare congenital disorder, called BPTAS, which is characterized mainly by limb malformations including smaller-than-normal or extra fingers or toes and absent or underdeveloped shin bones. Researchers identified two de novo frameshift variants in <em>HMGB1<\/em> in five patients and in their subsequent functional analyses they revealed a pathomechanism that might also be relevant for other rare diseases.<\/p>\n<p><em>HMGB1<\/em> encodes high mobility group box protein 1, a nuclear protein involved for example in DNA organization and transcription. In its protein structure, HMGB1 has an intrinsically disordered region. Such flexible regions in proteins can play an important role in the partitioning of membrane-free structures by promoting the formation of protein droplets. The nucleolus is an essential cellular organelle within the nucleus that does not possess a membrane. It is the place where subunits of the ribosomes are synthesized. The researchers discovered that the identified <em>HMGB1<\/em> variants lead to the formation of an arginine-rich basic tail replacing the protein\u2019s intrinsically disordered region. This results in a change of the protein\u2019s charge, affecting the process of phase separation in the nucleolus and impairing its function. The authors assume that this mechanism may also be relevant for a large number of similar variants in other genes, if they affect intrinsically disordered protein regions.<\/p>\n<p>The study led by scientists from Berlin Charit\u00e9 and Max-Planck Institute for Molecular Genetics as well as Schleswig-Holstein University Hospital has been published in <em>Nature<\/em>.<\/p>\n[vc_column_text] Mensah MA, Niskanen H, Magalhaes AP, \u2026 Spielmann M, Horn D, Hnisz D. Aberrant phase separation and nucleolar dysfunction in rare genetic diseases. <em>Nature<\/em>. 2023 Feb;614(7948):564-571. doi: 10.1038\/s41586-022-05682-1. Epub 2023 Feb 8. [\/vc_column_text]\n[mk_button dimension=&#8221;flat&#8221; size=&#8221;medium&#8221; icon=&#8221;mk-icon-long-arrow-right&#8221; icon_anim=&#8221;side&#8221; url=&#8221;https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/36755093&#8243; target=&#8221;_blank&#8221; bg_color=&#8221;#006699&#8243; btn_hover_bg=&#8221;#000000&#8243; btn_hover_txt_color=&#8221;#ffffff&#8221;]Article in PubMed[\/mk_button][mk_padding_divider size=&#8221;30&#8243;]\n","protected":false},"excerpt":{"rendered":"<p>Specific heterozygous variants in HMGB1 cause an extremely rare congenital disorder, called BPTAS, which is characterized mainly by limb malformations including smaller-than-normal or extra fingers or toes and absent or underdeveloped shin bones. Researchers identified two de novo frameshift variants in HMGB1 in five patients and in their subsequent functional analyses they revealed a pathomechanism [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[54],"tags":[],"class_list":["post-12785","post","type-post","status-publish","format-standard","hentry","category-gene-of-the-month"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Gene of the Month - February: HMGB1 - Institut f\u00fcr Humangenetik<\/title>\n<meta name=\"description\" content=\"Specific heterozygous variants in HMGB1 cause the extremely rare congenital disorder BPTAS, which is characterized mainly by limb malformations.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-hmgb1\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Gene of the Month - February: HMGB1 - Institut f\u00fcr Humangenetik\" \/>\n<meta property=\"og:description\" content=\"Specific heterozygous variants in HMGB1 cause the extremely rare congenital disorder BPTAS, which is characterized mainly by limb malformations.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-hmgb1\/\" \/>\n<meta property=\"og:site_name\" content=\"Institut f\u00fcr Humangenetik\" \/>\n<meta property=\"article:published_time\" content=\"2023-03-01T13:31:32+00:00\" \/>\n<meta name=\"author\" content=\"KB\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"KB\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-hmgb1\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-hmgb1\/\"},\"author\":{\"name\":\"KB\",\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/#\/schema\/person\/521bbb2a6ceb55060a1ef5eccb794675\"},\"headline\":\"Gene of the Month &#8211; 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