Evidence map›Paper›PMID 39737487›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Nour Elkhateeb, Renarta Crookes, Michael Spiller, Lisa Pavinato, Flavia Palermo, Alfredo Brusco, Michael Parker, Soo-Mi Park, Ariana Costa Mendes, Jorge M Saraiva and 61 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. medRxiv : the preprint server for health sciences · 2025
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4 · The record

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5 · Who and what money

Authors and funding

71 authors.

Nour ElkhateebDepartment of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. Electronic address: nour.elkhateeb@nhs.net.
Renarta CrookesSheffield Diagnostic Genetics Service, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom.
Michael SpillerSheffield Diagnostic Genetics Service, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom.
Lisa PavinatoDepartment of Medical Sciences, University of Turin, Turin, Italy; Institute of Oncology Research (IOR), Bellinzona Institutes of Science (BIOS(+)), Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
Flavia PalermoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Alfredo BruscoDepartment of Neurosciences Rita Levi-Montalcini, University of Turin, Turin, Italy; Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy.
Michael ParkerSheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
Soo-Mi ParkDepartment of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Ariana Costa MendesMedical Genetics Department, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Jorge M SaraivaMedical Genetics Department, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal; University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Portugal; Clinical Academic Center of Coimbra, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Trine Bjørg HammerDepartment of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark; Department of Genetics, Rigshospitalet, Copenhagen, Denmark.
Lusine Nazaryan-PetersenDepartment of Genetics, Rigshospitalet, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tahsin Stefan BarakatDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Discovery Unit, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Martina WilkeDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Elizabeth BhojDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Rebecca C Ahrens-NicklasDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Dong LiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Tomoki NomakuchiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Eva H BrilstraDepartment of Genetics and Brain Center, University Medical Center Utrecht, The Netherlands.
David HuntWessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, United Kingdom.
Diana JohnsonSheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
Sahar MansourSouth West Thames Regional Genetics Service, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; School of Biological and Molecular Sciences, St George's University of London, London, United Kingdom.
Kathryn OprychSouth West Thames Regional Genetics Service, St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
Sarju G MehtaDepartment of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Division of Neuropaediatrics, Hospital for Children and Adolescents, University Hospital Leipzig, Leipzig, Germany.
Franziska SchnabelInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Division of Neuropaediatrics, Hospital for Children and Adolescents, University Hospital Leipzig, Leipzig, Germany.
Henriette KiepInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Division of Neuropaediatrics, Hospital for Children and Adolescents, University Hospital Leipzig, Leipzig, Germany.
Helene FaustInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Division of Neuropaediatrics, Hospital for Children and Adolescents, University Hospital Leipzig, Leipzig, Germany.
Gillian PrinzingDepartment of Neurology, Boston Children's Hospital, Boston, MA.
Kimberly WiltroutDepartment of Neurology, Boston Children's Hospital, Boston, MA.
Jessica A RadleyNorth West Thames Regional Genomics Service, London North West University Healthcare NHS Trust, Northwick Park Hospital, United Kingdom.
Alvaro H Serrano RussiDivision of Genetics, Department of Pediatrics, East Tennessee State University (ETSU), Quillen College of Medicine, TN.
Isis AtallahDivision of Genetic Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Belinda Campos-XavierDivision of Genetic Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
David J AmorSpeech and Language, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Angela T MorganSpeech and Language, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Christina FagerbergDepartment of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Genetics, Lillebaelt Hospital, location Vejle Hospital, Vejle, Denmark.
Ulla A AndersenDepartment of Mental Health, Odense University Hospital, Odense, Denmark.
Charlotte B AndersenDepartment of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Emilia K BijlsmaDepartment of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Lynne M BirdDivision of Genetics and Dysmorphology, Department of Pediatrics, University of California San Diego, Rady Children's Hospital, San Diego, CA.
Sureni V MullegamaGeneDx, Gaithersburg, MD.
Andrew GreenDepartment of Clinical Genetics, Children's Health Ireland at Crumlin, Dublin, Ireland; University College Dublin School of Medicine and Medical Science, Dublin, Ireland.
Bertrand IsidorNantes Université, CNRS, INSERM, l'institut du thorax, Nantes, France; CHU Nantes, Service de Génétique Médicale, Nantes Université, CNRS, INSERM, l'institut du thorax, Nantes, France.
Benjamin CognéNantes Université, CNRS, INSERM, l'institut du thorax, Nantes, France.
Janna KennyDepartment of Clinical Genetics, Children's Health Ireland at Crumlin, Dublin, Ireland.
Sally A LynchDepartment of Clinical Genetics, Children's Health Ireland at Crumlin, Dublin, Ireland.
Shauna QuinDepartment of Clinical Genetics, Children's Health Ireland at Crumlin, Dublin, Ireland.
Karen LowDepartment of Clinical Genetics, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom; Bristol Medical School, University of Bristol, United Kingdom.
Theresia HergetInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Fanny KortümInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Rebecca J LevyNeurology and Neurological Sciences, Division of Child Neurology, Stanford University and Lucile Packard Children's Hospital, Palo Alto, CA.
Jennifer L MorrisonDivision of Genetics, Arnold Palmer Hospital for Children, Orlando, FL.
Patricia G WheelerDivision of Genetics, Arnold Palmer Hospital for Children, Orlando, FL.
TaraChandra NarumanchDivision of Genetics, Department of Pediatrics, West Virginia University, Morgantown, WV.
Kristina PeronDivision of Genetics, Department of Pediatrics, West Virginia University, Morgantown, WV.
Nicole MatthewsDivision of Genetics, Department of Pediatrics, West Virginia University, Morgantown, WV.
Jillian UhlmanUniversity of Illinois College of Medicine, Peoria, IL.
Lauren BellUniversity of Illinois College of Medicine, Peoria, IL.
Lewis PangExeter Genomics Laboratory, RILD Building, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
Ingrid ScurrDepartment of Clinical Genetics, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom.
Rebecca S BellesGeisinger Health System, Danville, PA.
Bonnie Anne SalbertGeisinger Health System, Danville, PA.
Gerald Bradley SchaeferUniversity of Arkansas for Medical Sciences, Little Rock, AR.
Sarah GreenUniversity of Arkansas for Medical Sciences, Little Rock, AR.
Andrea RosDepartment of Genetics, Hospital Universitari Germans Trias i Pujol, Catalonia, Spain.
Agustí Rodríguez-PalmeroPediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Catalonia, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
Tanja VišnjarClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Karin WritzlClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Pradeep C VasudevanDepartment of Clinical Genetics, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
Meena BalasubramanianSheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom; Division of Clinical Medicine, University of Sheffield, Sheffield, United Kingdom. Electronic address: m.balasubramanian@sheffield.ac.uk.

Funding

MEDICAL GENETICS RESEARCH TRAINING GRANTT32GM008638 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca Ganetzky · 1997 to 2026
$8.7M
Medical Research Council MR/V037307/1NIGMS NIH HHS T32 GM008638Wellcome TrustWellcome Trust WT098051, 223718/Z/21/Z
6 · The paper itself

Abstract

purposeThe thousand and one kinase (TAOK) proteins are a group of serine/threonine-protein kinases involved in signaling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia, and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity. However, a distinct TAOK2-NDD has not yet been delineated.

methodsWe retrospectively studied the clinical and genetic data of individuals recruited from several centers with TAOK1 and TAOK2 variants that were detected through exome and genome sequencing.

resultsWe report 50 individuals with TAOK1 variants with associated phenotypes, including neurodevelopmental abnormalities (100%), macrocephaly (83%), and hypotonia (58%). We report male genital anomalies and hypoglycemia as novel phenotypes. Thirty-seven unique TAOK1 variants were identified. Most of the missense variants clustered in the protein kinase domain at residues that are intolerant to missense variation. We report 10 individuals with TAOK2 variants with associated phenotypes, including neurodevelopmental abnormalities (100%), macrocephaly (75%), autism (75%), and obesity (70%).

conclusionWe describe the largest cohort of TAOK1-NDD to date, to our knowledge, expanding its phenotype and genotype spectrum with 30 novel variants. We delineated the phenotype of a novel TAOK2-NDD associated with neurodevelopmental abnormalities, autism, macrocephaly, and obesity.

Indexed as

Neurodevelopmental DisordersProtein Serine-Threonine KinasesAdolescentAdultAutistic DisorderChildChild, PreschoolExome SequencingFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInfantMaleMegalencephalyProtein Serine-Threonine KinasesMAP3K enzymesNeurodevelopmental disorderTAOK1TAOK2Thousand and one kinase family

Identifiers

PMID39737487
PMCPMC13479925

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