{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Groeneweg S"],"funding":["NIMH NIH HHS","Wellcome Trust","EC | Eurostars"],"pagination":["2479"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11904026"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effec"],"journal":["Nature communications"],"pubmed_title":["Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration."],"pmcid":["PMC11904026"],"funding_grant_id":["210755/Z/18/Z","E113377","R01 MH118281"],"pubmed_authors":["van Wermeskerken AM","Seven Menevse T","Stals MAM","Klosowska A","Stegenga MT","Gallichan J","Tonduti D","van den Berg SAA","Gevers EF","van der Walt A","de Rooij LJ","van den Akker ELT","Stoupa A","Martin M","Groeneweg S","Koolen DA","Moran C","Huynh T","Barca D","Lyons G","McGowan A","Turan S","Poswar FO","Konrad D","Rozenkova K","Armour CM","Halasz Z","George B","Lunsing RJ","Visser WE","Crock P","Zung A","Coutant R","van Geest FS","Craiu D","Marks DS","Dubey R","Dolcetta-Capuzzo A","de Coo IFM","Hackenberg A","Lebl J","van den Berge A","Lorea CF","Paone L","Nicola JP","Wemeau JL","Rivadeneira F","Lourenco CM","Simon A","Abaci A","Leeuwenburgh S","Ambegaonkar GP","Teumer A","Bacos I","Meima ME","Medina-Gomez C","Brunner D","Singh Y","de Wit MY","Chatterjee K","Lawson-Yuen A","Wierzba J","DeGoede C","Malikova JK","Reinauer C","Wang H","Seckold R","Coenen-van der Spek J","Christian P","Kulkarni A","Mericq V","Lora FM","Spada M","Vanderniet J","Bertini E","Linder-Lucht M","Krude H","Chen CH","Fairchild J","Mancilla EE","Demir K","Castiglioni C","Paul PG","Cappa M","Frazer J","Oliver-Petit I","Wurm M","Laemmle A","Chesover A","Muller KE","Subramanian GM","Sterenborg RBTM","Bakhtiani P","Cappuccio G","Zwaveling-Soonawala N","Greenup E","Dica A","Simm P","Szeifert L","Isaza AR","Porta F","Wolf NI","Castellotti B","Hurst AC","Brunetti-Pierri N","Zibordi F","Dimitri P","Heinrich B","Lopez Marti A","McCormick KL","Dewey C","Bauer AJ","Enderli A","Garibaldi L","van der Knoop MM","LaFranchi SH","Nicol LE","Polak M","Dias M","Medici M","van Beynum IM","Dremmen MHG"],"additional_accession":[]},"is_claimable":false,"name":"Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration.","description":"Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effec","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-02T17:27:17.658Z","creation":"2025-04-05T22:11:35.373Z"},"accession":"S-EPMC11904026","cross_references":{"pubmed":["40075072"],"doi":["10.1038/s41467-025-56628-w"]}}