{"id":14731,"date":"2025-11-03T15:17:45","date_gmt":"2025-11-03T14:17:45","guid":{"rendered":"https:\/\/www.humangenetik-umg.de\/?p=14731"},"modified":"2025-11-03T15:17:45","modified_gmt":"2025-11-03T14:17:45","slug":"gene-of-the-month-october-ldlr","status":"publish","type":"post","link":"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-october-ldlr\/","title":{"rendered":"Gene of the Month \u2013 October: LDLR"},"content":{"rendered":"<p>A study recently published in <em>Science<\/em> systematically maps the functional impact of nearly all approximately 17,000 possible missense variants in the <em>LDLR<\/em> gene. The comprehensive functional data generated by an international team of researchers will facilitate the precise classification of previously unclear <em>LDLR<\/em> variants, improve risk prediction for familial hypercholesterinemia and support early intervention strategies.<\/p>\n<p><em>LDLR<\/em> encodes the low density lipoprotein receptor, primarily expressed on liver cells, which mediates the uptake of LDL from the bloodstream. Pathogenic <em>LDLR<\/em> variants are the main genetic cause of familial hypercholesterinemia. This condition is characterized by markedly elevated circulating LDL cholesterol from childhood and adolescence, leading, if untreated, to premature atherosclerosis and an increased risk of myocardial infarction and stroke at an early age. Heterozygous familial hypercholesterinemia is one of the most common genetic disorders, yet it is frequently only diagnosed after a myocardial infarction occurs in a young patient or if there is a family clustering of cardiovascular events. This is also due to the fact that most identified missense variants in <em>LDLR<\/em> lack definitive classification regarding their pathogenicity.<\/p>\n<p>The authors of the current study used a multiplexed <em>in vitro<\/em> assay to measure the impact of nearly all possible LDRL protein missense variants on LDL uptake and cell-surface abundance of LDL receptors. For over 7,000 of these LDLR missense variants, they generated and validated specific functional scores, which may now be used for the interpretation of previously ambiguous variants, helping to improve risk prediction and therapeutic intervention in patients and their families.<\/p>\n[vc_column_text]Tabet DR, Cot\u00e9 AG, Lancaster MC, \u2026 Roth FP. The functional landscape of coding variation in the familial hypercholesterolemia gene <em>LDLR<\/em>. <em>Science<\/em>. 2025 Oct 30:eady7186. doi: 10.1126\/science.ady7186. 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\/41166440&#8243; target=&#8221;_blank&#8221; bg_color=&#8221;#006699&#8243; btn_hover_bg=&#8221;#000000&#8243; btn_hover_txt_color=&#8221;#ffffff&#8221;]To Article in PubMed[\/mk_button][mk_padding_divider size=&#8221;30&#8243;]\n","protected":false},"excerpt":{"rendered":"<p>A study recently published in Science systematically maps the functional impact of nearly all approximately 17,000 possible missense variants in the LDLR gene. The comprehensive functional data generated by an international team of researchers will facilitate the precise classification of previously unclear LDLR variants, improve risk prediction for familial hypercholesterinemia and support early intervention strategies. [&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-14731","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 October: LDLR - Institut f\u00fcr Humangenetik<\/title>\n<meta name=\"description\" content=\"A study recently published in Science systematically maps the functional impact of nearly all approximately 17,000 possible missense variants in the LDLR gene.\" \/>\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-october-ldlr\/\" \/>\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 October: LDLR - 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