Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration
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 ne...
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2025-03-01
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| author | Stefan Groeneweg Ferdy S. van Geest Mariano Martín Mafalda Dias Jonathan Frazer Carolina Medina-Gomez Rosalie B. T. M. Sterenborg Hao Wang Anna Dolcetta-Capuzzo Linda J. de Rooij Alexander Teumer Ayhan Abaci Erica L. T. van den Akker Gautam P. Ambegaonkar Christine M. Armour Iiuliu Bacos Priyanka Bakhtiani Diana Barca Andrew J. Bauer Sjoerd A. A. van den Berg Amanda van den Berge Enrico Bertini Ingrid M. van Beynum Nicola Brunetti-Pierri Doris Brunner Marco Cappa Gerarda Cappuccio Barbara Castellotti Claudia Castiglioni Krishna Chatterjee Alexander Chesover Peter Christian Jet Coenen-van der Spek Irenaeus F. M. de Coo Regis Coutant Dana Craiu Patricia Crock Christian DeGoede Korcan Demir Cheyenne Dewey Alice Dica Paul Dimitri Marjolein H. G. Dremmen Rachana Dubey Anina Enderli Jan Fairchild Jonathan Gallichan Luigi Garibaldi Belinda George Evelien F. Gevers Erin Greenup Annette Hackenberg Zita Halász Bianka Heinrich Anna C. Hurst Tony Huynh Amber R. Isaza Anna Klosowska Marieke M. van der Knoop Daniel Konrad David A. Koolen Heiko Krude Abhishek Kulkarni Alexander Laemmle Stephen H. LaFranchi Amy Lawson-Yuen Jan Lebl Selmar Leeuwenburgh Michaela Linder-Lucht Anna López Martí Cláudia F. Lorea Charles M. Lourenço Roelineke J. Lunsing Greta Lyons Jana Krenek Malikova Edna E. Mancilla Kenneth L. McCormick Anne McGowan Veronica Mericq Felipe Monti Lora Carla Moran Katalin E. Muller Lindsey E. Nicol Isabelle Oliver-Petit Laura Paone Praveen G. Paul Michel Polak Francesco Porta Fabiano O. Poswar Christina Reinauer Klara Rozenkova Rowen Seckold Tuba Seven Menevse Peter Simm Anna Simon Yogen Singh Marco Spada Milou A. M. Stals Merel T. Stegenga Athanasia Stoupa Gopinath M. Subramanian Lilla Szeifert Davide Tonduti Serap Turan Joel Vanderniet Adri van der Walt Jean-Louis Wémeau Anne-Marie van Wermeskerken Jolanta Wierzba Marie-Claire Y. de Wit Nicole I. Wolf Michael Wurm Federica Zibordi Amnon Zung Nitash Zwaveling-Soonawala Fernando Rivadeneira Marcel E. Meima Debora S. Marks Juan P. Nicola Chi-Hua Chen Marco Medici W. Edward Visser |
| author_facet | Stefan Groeneweg Ferdy S. van Geest Mariano Martín Mafalda Dias Jonathan Frazer Carolina Medina-Gomez Rosalie B. T. M. Sterenborg Hao Wang Anna Dolcetta-Capuzzo Linda J. de Rooij Alexander Teumer Ayhan Abaci Erica L. T. van den Akker Gautam P. Ambegaonkar Christine M. Armour Iiuliu Bacos Priyanka Bakhtiani Diana Barca Andrew J. Bauer Sjoerd A. A. van den Berg Amanda van den Berge Enrico Bertini Ingrid M. van Beynum Nicola Brunetti-Pierri Doris Brunner Marco Cappa Gerarda Cappuccio Barbara Castellotti Claudia Castiglioni Krishna Chatterjee Alexander Chesover Peter Christian Jet Coenen-van der Spek Irenaeus F. M. de Coo Regis Coutant Dana Craiu Patricia Crock Christian DeGoede Korcan Demir Cheyenne Dewey Alice Dica Paul Dimitri Marjolein H. G. Dremmen Rachana Dubey Anina Enderli Jan Fairchild Jonathan Gallichan Luigi Garibaldi Belinda George Evelien F. Gevers Erin Greenup Annette Hackenberg Zita Halász Bianka Heinrich Anna C. Hurst Tony Huynh Amber R. Isaza Anna Klosowska Marieke M. van der Knoop Daniel Konrad David A. Koolen Heiko Krude Abhishek Kulkarni Alexander Laemmle Stephen H. LaFranchi Amy Lawson-Yuen Jan Lebl Selmar Leeuwenburgh Michaela Linder-Lucht Anna López Martí Cláudia F. Lorea Charles M. Lourenço Roelineke J. Lunsing Greta Lyons Jana Krenek Malikova Edna E. Mancilla Kenneth L. McCormick Anne McGowan Veronica Mericq Felipe Monti Lora Carla Moran Katalin E. Muller Lindsey E. Nicol Isabelle Oliver-Petit Laura Paone Praveen G. Paul Michel Polak Francesco Porta Fabiano O. Poswar Christina Reinauer Klara Rozenkova Rowen Seckold Tuba Seven Menevse Peter Simm Anna Simon Yogen Singh Marco Spada Milou A. M. Stals Merel T. Stegenga Athanasia Stoupa Gopinath M. Subramanian Lilla Szeifert Davide Tonduti Serap Turan Joel Vanderniet Adri van der Walt Jean-Louis Wémeau Anne-Marie van Wermeskerken Jolanta Wierzba Marie-Claire Y. de Wit Nicole I. Wolf Michael Wurm Federica Zibordi Amnon Zung Nitash Zwaveling-Soonawala Fernando Rivadeneira Marcel E. Meima Debora S. Marks Juan P. Nicola Chi-Hua Chen Marco Medici W. Edward Visser |
| author_sort | Stefan Groeneweg |
| collection | DOAJ |
| description | 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 effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders. |
| format | Article |
| id | doaj-art-0de7590ce33f4dff8cde3e316c92a6e6 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0de7590ce33f4dff8cde3e316c92a6e62025-08-20T03:01:38ZengNature PortfolioNature Communications2041-17232025-03-0116112110.1038/s41467-025-56628-wMapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integrationStefan Groeneweg0Ferdy S. van Geest1Mariano Martín2Mafalda Dias3Jonathan Frazer4Carolina Medina-Gomez5Rosalie B. T. M. Sterenborg6Hao Wang7Anna Dolcetta-Capuzzo8Linda J. de Rooij9Alexander Teumer10Ayhan Abaci11Erica L. T. van den Akker12Gautam P. Ambegaonkar13Christine M. Armour14Iiuliu Bacos15Priyanka Bakhtiani16Diana Barca17Andrew J. Bauer18Sjoerd A. A. van den Berg19Amanda van den Berge20Enrico Bertini21Ingrid M. van Beynum22Nicola Brunetti-Pierri23Doris Brunner24Marco Cappa25Gerarda Cappuccio26Barbara Castellotti27Claudia Castiglioni28Krishna Chatterjee29Alexander Chesover30Peter Christian31Jet Coenen-van der Spek32Irenaeus F. M. de Coo33Regis Coutant34Dana Craiu35Patricia Crock36Christian DeGoede37Korcan Demir38Cheyenne Dewey39Alice Dica40Paul Dimitri41Marjolein H. G. Dremmen42Rachana Dubey43Anina Enderli44Jan Fairchild45Jonathan Gallichan46Luigi Garibaldi47Belinda George48Evelien F. Gevers49Erin Greenup50Annette Hackenberg51Zita Halász52Bianka Heinrich53Anna C. Hurst54Tony Huynh55Amber R. Isaza56Anna Klosowska57Marieke M. van der Knoop58Daniel Konrad59David A. Koolen60Heiko Krude61Abhishek Kulkarni62Alexander Laemmle63Stephen H. LaFranchi64Amy Lawson-Yuen65Jan Lebl66Selmar Leeuwenburgh67Michaela Linder-Lucht68Anna López Martí69Cláudia F. Lorea70Charles M. Lourenço71Roelineke J. Lunsing72Greta Lyons73Jana Krenek Malikova74Edna E. Mancilla75Kenneth L. McCormick76Anne McGowan77Veronica Mericq78Felipe Monti Lora79Carla Moran80Katalin E. Muller81Lindsey E. Nicol82Isabelle Oliver-Petit83Laura Paone84Praveen G. Paul85Michel Polak86Francesco Porta87Fabiano O. Poswar88Christina Reinauer89Klara Rozenkova90Rowen Seckold91Tuba Seven Menevse92Peter Simm93Anna Simon94Yogen Singh95Marco Spada96Milou A. M. Stals97Merel T. Stegenga98Athanasia Stoupa99Gopinath M. Subramanian100Lilla Szeifert101Davide Tonduti102Serap Turan103Joel Vanderniet104Adri van der Walt105Jean-Louis Wémeau106Anne-Marie van Wermeskerken107Jolanta Wierzba108Marie-Claire Y. de Wit109Nicole I. Wolf110Michael Wurm111Federica Zibordi112Amnon Zung113Nitash Zwaveling-Soonawala114Fernando Rivadeneira115Marcel E. Meima116Debora S. Marks117Juan P. Nicola118Chi-Hua Chen119Marco Medici120W. Edward Visser121Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreDepartment of Clinical Biochemistry (CIBICI-CONICET), Faculty of Chemical Sciences, National University of CórdobaDepartment of Systems Biology, Harvard Medical SchoolDepartment of Systems Biology, Harvard Medical SchoolDepartment of Internal Medicine, Erasmus University Medical CenterAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreCenter for Multimodal Imaging and Genetics, University of California San DiegoAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreDepartment of Psychiatry and Psychotherapy, University Medicine GreifswaldDivision of Pediatric Endocrinology, Faculty of Medicine, Dokuz Eylul UniversityDepartment of Paediatrics, Division of Endocrinology, Erasmus Medical Centre -Sophia Children’s HospitalDepartment of Paediatric Neurology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation TrustRegional Genetics Program, Children’s Hospital of Eastern Ontario and Children’s Hospital of Eastern Ontario Research Institute, University of OttawaCentrul Medical Dr. Bacos CosmaUniversity of LouisvilleCarol Davila University of Medicine, Department of Clinical Neurosciences, Paediatric Neurology Discipline IIDivision of Endocrinology and Diabetes, Children’s Hospital of PhiladelphiaDiagnostic Laboratory for Endocrinology, Department of Internal Medicine, Erasmus Medical CenterAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreUnit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu’ Children’s Research Hospital IRCCSDepartment of Pediatrics, Division of Pediatric Cardiology, Erasmus Medical Centre - Sophia Children’s HospitalDepartment of Translational Medicine, Federico II UniversityGottfried Preyer’s Children HospitalResearch Area for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCSDepartment of Translational Medicine, Federico II UniversityUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaDepartment of Neurology, Clinica Meds, School of Medicine, Universidad Finis TerraeWellcome Trust-Medical Research Council Institute of Metabolic Science, University of CambridgeDivision of Endocrinology, The Hospital for Sick Children and Department of Paediatrics, University of TorontoEast Kent Hospitals University NHS Foundation TrustDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center (Radboudumc)Department of Toxicogenomics, Unit Clinical Genomics, Maastricht University, MHeNs School for Mental Health and NeuroscienceDepartment of Pediatric Endocrinology and Diabetology, University HospitalCarol Davila University of Medicine, Department of Clinical Neurosciences, Paediatric Neurology Discipline IIJohn Hunter Children’s Hospital, Hunter Medical Research Institute, University of NewcastleDepartment of Paediatric Neurology, Clinical Research Facility, Lancashire Teaching Hospitals NHS TrustDivision of Pediatric Endocrinology, Faculty of Medicine, Dokuz Eylul UniversityGenomics Institute Mary Bridge Children’s Hospital, MultiCare Health SystemCarol Davila University of Medicine, Department of Clinical Neurosciences, Paediatric Neurology Discipline IIThe Department of Oncology and Metabolism, The University of Sheffield, Western BankDivision of Paediatric Radiology, Erasmus Medical Centre – Sophia’s Children HospitalMedanta Superspeciality HospitalDepartment of Neuropediatrics, University Children’s Hospital, University of ZurichDepartment of Diabetes and Endocrinology, Women’s and Children’s HospitalPlymouth Hospitals NHS TrustUPMC Children’s Hospital of PittsburghDepartment of Endocrinology, St. John’s Medical College HospitalCentre for Endocrinology, William Harvey Research institute, Queen Mary University of LondonDepartment of Pediatrics, Division of Pediatric Endocrinology, University of Alabama at BirminghamDepartment of Neuropediatrics, University Children’s Hospital, University of ZurichPediatric Center, Semmelweis University BudapestDepartment of Neuropediatrics, University Children’s Hospital, University of ZurichDepartment of Genetics, University of Alabama at BirminghamDepartment of Endocrinology & Diabetes, Queensland Children’s Hospital, South BrisbaneDivision of Endocrinology and Diabetes, Children’s Hospital of PhiladelphiaDepartment of Pediatrics, Hematology and Oncology, Medical University of GdańskDepartment of Paediatric Neurology, Erasmus Medical CentreDivision of Pediatric Endocrinology and Diabetology and Children’s Research Center, University Children’s Hospital, University of ZurichDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center (Radboudumc)Institute of Experimental Paediatric Endocrinology, Charité-Universitätsmedizin BerlinDepartment of Paediatric Endocrinology, SRCC Children’s HospitalInstitute of Clinical Chemistry and Department of Pediatrics, Inselspital, University Hospital BernDepartment of Pediatrics, Doernbecher Children’s Hospital, Oregon Health & Sciences UniversityGenomics Institute Mary Bridge Children’s Hospital, MultiCare Health SystemDepartment of Paediatrics, Second Faculty of Medicine, Charles University, University Hospital MotolAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreDivision of Neuropediatrics and Muscular Disorders, Department of Pediatrics and Adolescent Medicine, University Hospital FreiburgAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreTeaching Hospital of Universidade Federal de PelotasNational Reference Center for Rare Diseases, Faculdade de Medicina de São José do Rio PretoDepartment of Child Neurology, University Medical Center Groningen, University of GroningenWellcome Trust-Medical Research Council Institute of Metabolic Science, University of CambridgeDepartment of Paediatrics, Second Faculty of Medicine, Charles University, University Hospital MotolDivision of Endocrinology and Diabetes, Children’s Hospital of PhiladelphiaDepartment of Pediatrics, Division of Pediatric Endocrinology, University of Alabama at BirminghamWellcome Trust-Medical Research Council Institute of Metabolic Science, University of CambridgeInstitute of Maternal and Child Research, University of Chile, Santiago, Chile, Department of Pediatrics, Clinica Las CondesPediatric Endocrinology Group, Sabara Children’s HospitalWellcome Trust-Medical Research Council Institute of Metabolic Science, University of CambridgeHeim Pal National Pediatric InstituteDepartment of Pediatrics, Doernbecher Children’s Hospital, Oregon Health & Sciences UniversityDepartment of Paediatric Endocrinology and Genetics, Children’s Hospital, Toulouse University HospitalEndocrinology and Diabetology Unit, Bambino Gesù Children’s Hospital, IRCCSDepartment of Paediatrics, Christian Medical CollegePaediatric Endocrinology, Diabetology and Gynaecology, Department, Necker Children’s University Hospital, Imagine Institute Affiliate, Université de Paris CitéDepartment of Paediatrics, AOU Città della Salute e della Scienza di Torino, University of TorinoMedical Genetics Service, Hospital de Clínicas de Porto AlegreDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Medical FacultyDepartment of Paediatrics, Second Faculty of Medicine, Charles University, University Hospital MotolJohn Hunter Children’s Hospital, Hunter Medical Research Institute, University of NewcastleMarmara University School of Medicine Department of Pediatric EndocrinologyRoyal Children’s Hospital/University of MelbourneDepartment of Paediatrics, Christian Medical CollegeDepartment of Paediatric Cardiology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation TrustDepartment of Paediatrics, AOU Città della Salute e della Scienza di Torino, University of TorinoAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentrePaediatric Endocrinology, Diabetology and Gynaecology, Department, Necker Children’s University Hospital, Imagine Institute Affiliate, Université de Paris CitéJohn Hunter Children’s Hospital, Hunter Medical Research Institute, University of NewcastlePediatric Center, Semmelweis University BudapestChild Neurology Unit - C.O.A.L.A. (Center for diagnosis and treatment of leukodystrophies), V. Buzzi Children’s HospitalMarmara University School of Medicine Department of Pediatric EndocrinologyJohn Hunter Children’s Hospital, Hunter Medical Research Institute, University of NewcastlePrivate paediatric Neurology practice Dr A van der WaltUniversity of LilleDepartment of Paediatrics, FlevoziekenhuisDepartment of Internal and Pediatric Nursing, Institute of Nursing and Midwifery, Medical University of GdańskDepartment of Paediatric Neurology, Erasmus Medical CentreDepartment of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children’s Hospital, Amsterdam University Medical Centers, Vrije Universiteit AmsterdamUniversity Children’s Hospital Regensburg (KUNO), University of Regensburg, Campus St. HedwigChild Neurology Unit, Fondazione IRCCS, Istituto Neurologico Carlo BestaPediatric Endocrinology Unit, Kaplan Medical center, Rehovot and the Hebrew University of JerusalemEmma Children’s Hospital, Department of Paediatric Endocrinology, Amsterdam UMC, University of AmsterdamDepartment of Internal Medicine, Erasmus University Medical CenterAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreDepartment of Systems Biology, Harvard Medical SchoolDepartment of Clinical Biochemistry (CIBICI-CONICET), Faculty of Chemical Sciences, National University of CórdobaCenter for Multimodal Imaging and Genetics, University of California San DiegoAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical CentreAbstract 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 effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders.https://doi.org/10.1038/s41467-025-56628-w |
| spellingShingle | Stefan Groeneweg Ferdy S. van Geest Mariano Martín Mafalda Dias Jonathan Frazer Carolina Medina-Gomez Rosalie B. T. M. Sterenborg Hao Wang Anna Dolcetta-Capuzzo Linda J. de Rooij Alexander Teumer Ayhan Abaci Erica L. T. van den Akker Gautam P. Ambegaonkar Christine M. Armour Iiuliu Bacos Priyanka Bakhtiani Diana Barca Andrew J. Bauer Sjoerd A. A. van den Berg Amanda van den Berge Enrico Bertini Ingrid M. van Beynum Nicola Brunetti-Pierri Doris Brunner Marco Cappa Gerarda Cappuccio Barbara Castellotti Claudia Castiglioni Krishna Chatterjee Alexander Chesover Peter Christian Jet Coenen-van der Spek Irenaeus F. M. de Coo Regis Coutant Dana Craiu Patricia Crock Christian DeGoede Korcan Demir Cheyenne Dewey Alice Dica Paul Dimitri Marjolein H. G. Dremmen Rachana Dubey Anina Enderli Jan Fairchild Jonathan Gallichan Luigi Garibaldi Belinda George Evelien F. Gevers Erin Greenup Annette Hackenberg Zita Halász Bianka Heinrich Anna C. Hurst Tony Huynh Amber R. Isaza Anna Klosowska Marieke M. van der Knoop Daniel Konrad David A. Koolen Heiko Krude Abhishek Kulkarni Alexander Laemmle Stephen H. LaFranchi Amy Lawson-Yuen Jan Lebl Selmar Leeuwenburgh Michaela Linder-Lucht Anna López Martí Cláudia F. Lorea Charles M. Lourenço Roelineke J. Lunsing Greta Lyons Jana Krenek Malikova Edna E. Mancilla Kenneth L. McCormick Anne McGowan Veronica Mericq Felipe Monti Lora Carla Moran Katalin E. Muller Lindsey E. Nicol Isabelle Oliver-Petit Laura Paone Praveen G. Paul Michel Polak Francesco Porta Fabiano O. Poswar Christina Reinauer Klara Rozenkova Rowen Seckold Tuba Seven Menevse Peter Simm Anna Simon Yogen Singh Marco Spada Milou A. M. Stals Merel T. Stegenga Athanasia Stoupa Gopinath M. Subramanian Lilla Szeifert Davide Tonduti Serap Turan Joel Vanderniet Adri van der Walt Jean-Louis Wémeau Anne-Marie van Wermeskerken Jolanta Wierzba Marie-Claire Y. de Wit Nicole I. Wolf Michael Wurm Federica Zibordi Amnon Zung Nitash Zwaveling-Soonawala Fernando Rivadeneira Marcel E. Meima Debora S. Marks Juan P. Nicola Chi-Hua Chen Marco Medici W. Edward Visser Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration Nature Communications |
| title | Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration |
| title_full | Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration |
| title_fullStr | Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration |
| title_full_unstemmed | Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration |
| title_short | Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration |
| title_sort | mapping variants in thyroid hormone transporter mct8 to disease severity by genomic phenotypic functional structural and deep learning integration |
| url | https://doi.org/10.1038/s41467-025-56628-w |
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milouamstals mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT mereltstegenga mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT athanasiastoupa mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT gopinathmsubramanian mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT lillaszeifert mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT davidetonduti mappingvariantsinthyroidhormonetransportermct8todiseaseseveritybygenomicphenotypicfunctionalstructuralanddeeplearningintegration AT serapturan 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