{"id":14607,"date":"2025-09-01T10:13:45","date_gmt":"2025-09-01T08:13:45","guid":{"rendered":"https:\/\/www.humangenetik-umg.de\/?p=14607"},"modified":"2025-09-01T10:13:45","modified_gmt":"2025-09-01T08:13:45","slug":"gene-of-the-month-august-tgds","status":"publish","type":"post","link":"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-august-tgds\/","title":{"rendered":"Gene of the Month \u2013 August: TGDS"},"content":{"rendered":"<p><em>TGDS<\/em> acts as a \u201crescue molecule\u201d in sugar metabolism\u2014a previously unknown physiological function of the enzyme deoxy-TDP-D-glucose 4,6-dehydratase described now by researchers in <em>Nature<\/em>. The recently published study shows that TGDS is essential in a kind of emergency mechanism for the synthesis of UDP-xylose, a component required for building glycosaminoglycans. These long-chain sugar polymers are indispensable for bones, cartilage, and connective tissue. For the first time, the scientists provide a mechanism explaining the development of Catel-Manzke syndrome, a very rare hereditary skeletal disorder caused by homozygous or compound heterozygous pathogenic variants in the <em>TGDS<\/em> gene.<\/p>\n<p>Functional studies in a range of cell lines and a mouse model revealed that TGDS is tightly linked to the activity of UXS1 (UDP-glucuronate decarboxylase 1). This enzyme catalyzes the conversion of UDP-glucuronate to UDP-xylose, but can occasionally lose an intermediate metabolite and remain in an inactive form. As the researchers discovered, TGDS produces a kind of rescue molecule from UDP-glucose that allows UXS1 to become reactivated, enabling the enzymatic reaction to proceed. Deleterious variants in <em>TGDS<\/em>, however, prevent the reactivation of UXS1. Malfunction of such molecular rescue systems, like that involving TGDS and UXS1, may also play a role in the pathogenesis of other diseases.<\/p>\n[vc_column_text]Jacobs J, Lyubenova H, Potelle S, Kopp J, Gerin I, Chan WL, Rodriguez de Los Santos M, H\u00fclsemann W, Mensah MA, Cormier-Daire V, Joosten M, Bruggenwirth HT, Stuurman KE, Miranda V, Campeau PM, Wittler L, Graff J, Mundlos S, Ibrahim DM, Van Schaftingen E, Fischer-Zirnsak B, Kornak U, Ehmke N, Bommer GT. A missing enzyme-rescue metabolite as cause of a rare skeletal dysplasia. <em>Nature<\/em>. 2025 Aug 20. doi: 10.1038\/s41586-025-09397-x. Epub ahead of print. [\/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\/40836090&#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>TGDS acts as a \u201crescue molecule\u201d in sugar metabolism\u2014a previously unknown physiological function of the enzyme deoxy-TDP-D-glucose 4,6-dehydratase described now by researchers in Nature. The recently published study shows that TGDS is essential in a kind of emergency mechanism for the synthesis of UDP-xylose, a component required for building glycosaminoglycans. These long-chain sugar polymers are [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[54],"tags":[],"class_list":["post-14607","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 \u2013 August: TGDS - Institut f\u00fcr Humangenetik<\/title>\n<meta name=\"description\" content=\"TGDS acts as a \u201crescue molecule\u201d in sugar metabolism and causes Catel-Manzke syndrome.\" \/>\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-august-tgds\/\" \/>\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 \u2013 August: TGDS - 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