ArticleAmerican journal of human genetics2017
De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 107 papers.
0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
12.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
107 citing papers in PubMed, 197 citations in OpenAlex.
- CaMKIIα holoenzymes self-organize into chain-like mesoscale clusters.Science advances · 2026Article
- CaMKIIβ insufficiency disrupts cortical networks, producing aberrant low-gamma oscillations and seizure susceptibility.Epilepsia · 2026Article
- circRNA-Associated ceRNA Regulatory Networks in Cardiac Responses to High-Altitude Hypoxia in Tibetan Pigs (International journal of molecular sciences · 2026Article
- Urine-Derived iPSC Neurospheres Uncover Proteomic Correlates of Clinical Severity in Dravet Syndrome.Journal of neurochemistry · 2026Article
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- Brain-derived microvesicles induce activation of aspirin-treated platelets via the PLC/PKC pathway.Scientific reports · 2026Article
- A novel CFAP57 nonsense mutation causes asthenozoospermia in a consanguineous Emirati family.Molecular biology reports · 2026Article
- Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.Annals of clinical and translational neurology · 2026Article
- Genetic Traces in Autism Spectrum Disorders: A Whole Exome Sequencing Study from Türkiye.Genes · 2026Article
- Targeting the exosomal CaMK2A-ZDHHC3-GPX4 pathway reprograms tumor-associated macrophages and enhances anti-PD-1/PD-L1 immunotherapy in gastric cancer.International journal of biological sciences · 2026Article
- Functional characterization of a human epilepsy-associated gene network reveals metabolic regulation as a critical factor underlying seizure susceptibilities.Disease models & mechanisms · 2026Article
- Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases.bioRxiv : the preprint server for biology · 2025Article
- Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts.European journal of human genetics : EJHG · 2025Article
- A domain-swapped CaMKII conformation facilitates linker-mediated allosteric regulation.Nature communications · 2025Article
- Transcriptomic Signatures of Mitochondrial Dysfunction in Autism: Integrated mRNA and microRNA Profiling.Genes · 2025Article
- Identification and validation of a hypoxia- and immune-related prognostic signature for pancreatic cancer.Biochemistry and biophysics reports · 2025Article
- An AlphaFold guided model for the evolution of the CaMKII interactome.bioRxiv : the preprint server for biology · 2025Article
- MuSK is a substrate for CaMK2β but this interaction is dispensable for MuSK activation in vivo.Scientific reports · 2025Article
- Calcium/Calmodulin-Dependent Protein Kinase II β Regulates Autophagy Dependent Ferroptosis of Neurons after Cerebral Ischemic Injury by Activating the AREG/JUN/ELAVL1 Pathway.Neurochemical research · 2025Article
- A hyper-activatable CAMK2A variant associated with intellectual disability causes exaggerated long-term potentiation and learning impairments.Translational psychiatry · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
107 authors at 20 institutions in 9 countries.
Sébastien KüryCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France. Electronic address: sebastien.kury@chu-nantes.fr.
Geeske M van WoerdenDepartment of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Thomas BesnardCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Martina Proietti OnoriDepartment of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Xénia LatypovaCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Meghan C TowneDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Gene Discovery Core, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Megan T ChoGeneDx, Gaithersburg, MD 20877, USA.
Trine E PrescottDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Melissa A PloegDepartment of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Stephan SandersDepartment of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Holly A F StessmanDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA.
Aurora PujolNeurometabolic Diseases Laboratory, IDIBELL, Gran Via, 199, L'Hospitalet de Llobregat, 08908 Barcelona, and CIBERER U759, Center for Biomedical Research on Rare Diseases, 08908 Barcelona, Spain; Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.
Ben DistelDepartment of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, the Netherlands.
Laurie A RobakDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jonathan A BernsteinDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anne-Sophie Denommé-PichonCHU Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France; UMR INSERM 1083 - CNRS 6015, 49933 Angers Cedex 9, France.
Gaëtan LescaService de génétique, Centre de Référence des Anomalies du Développement, Hospices Civils de Lyon, 69288 Lyon, France; INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, 69675 Bron, France.
Elizabeth A SellarsSection of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, AR 72202, USA.
Jonathan BergMolecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.
Wilfrid CarréLaboratoire de Génétique Moléculaire & Génomique, CHU de Rennes, 35033 Rennes, France.
Øyvind Løvold BuskDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Bregje W M van BonDepartment of Human Genetics, Nijmegen Center for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, the Netherlands.
Jeff L WaughDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Matthew DeardorffDepartment of Pediatrics, Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
George E HogansonDepartment of Pediatrics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
Katherine B BosankoSection of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, AR 72202, USA.
Diana S JohnsonSheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK.
Tabib DabirNorthern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK.
Øystein Lunde HollaDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Ajoy SarkarNottingham Regional Genetics Service, City Hospital Campus, Nottingham University Hospitals NHS Trust, The Gables, Hucknall Road, Nottingham NG5 1PB, UK.
Kristian TvetenDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Julitta de BellescizeEpilepsy, Sleep and Pediatric Neurophysiology Department, Hospices Civils, Lyon, 69677 Bron, France.
Geir J BraathenDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Paulien A TerhalDepartment of Genetics, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands.
Dorothy K GrangeDivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Arie van HaeringenDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, the Netherlands.
Christina LamDivision of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA 98105, USA.
Ghayda MirzaaDivision of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA 98105, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Jennifer BurtonDepartment of Pediatrics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
Elizabeth J BhojCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Jessica DouglasDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Avni B SantaniDivision of Genomic Diagnostics, Department of Path and Lab Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Path and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, USA.
Addie I NesbittDivision of Genomic Diagnostics, Department of Path and Lab Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Katherine L HelbigDivision of Clinical Genomics, Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656, USA; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Marisa V AndrewsDivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Amber BegtrupGeneDx, Gaithersburg, MD 20877, USA.
Sha TangDivision of Clinical Genomics, Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656, USA.
Koen L I van GassenDepartment of Genetics, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands.
Jane JuusolaGeneDx, Gaithersburg, MD 20877, USA.
Kimberly FossCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Gregory M EnnsDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ute MoogInstitute of Human Genetics, University Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Katrin HinderhoferInstitute of Human Genetics, University Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Nagarajan ParamasivamMedical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany and Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Sharyn LincolnDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Brandon H KusakoDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Pierre LindenbaumINSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France; CHU Nantes, l'institut du thorax, 44093 Nantes, France.
Eric CharpentierINSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France; CHU Nantes, l'institut du thorax, 44093 Nantes, France.
Catherine B NowakDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Elouan CherotLaboratoire de Génétique Moléculaire & Génomique, CHU de Rennes, 35033 Rennes, France.
Thomas SimonetEpilepsy, Sleep and Pediatric Neurophysiology Department, Hospices Civils, Lyon, 69677 Bron, France.
Claudia A L RuivenkampDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, the Netherlands.
Sihoun HahnDivision of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA 98105, USA.
Catherine A BrownsteinDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Gene Discovery Core, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Fan XiaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77030, USA.
Sébastien SchmittCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Wallid DebCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Dominique BonneauCHU Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France; UMR INSERM 1083 - CNRS 6015, 49933 Angers Cedex 9, France.
Mathilde NizonCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Delphine QuinquisCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Jamel ChellyLaboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 67091 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67000 Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, 67404 Illkirch, France.
Gabrielle RudolfFédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67000 Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, 67404 Illkirch, France; Service of Neurology, University Hospital of Strasbourg, Hospital of Hautepierre, 1 avenue Molière, 67098 Strasbourg Cedex, France.
Damien SanlavilleService de génétique, Centre de Référence des Anomalies du Développement, Hospices Civils de Lyon, 69288 Lyon, France; INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, 69675 Bron, France.
Philippe ParentCHRU Brest, Génétique médicale, 29609 Brest, France.
Brigitte Gilbert-DussardierCHU Poitiers, Service de Génétique, BP577, 86021 Poitiers, France; EA 3808 Université Poitiers, France.
Annick ToutainCHU Tours, Service de Génétique, 2 Boulevard Tonnellé, 37044 Tours, France.
Vernon R SuttonBaylor Genetics, Houston, TX 77030, USA.
Jenny ThiesDivision of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA 98105, USA.
Lisenka E L M Peart-VissersDepartment of Human Genetics, Nijmegen Center for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, the Netherlands.
Pierre BoisseauCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Marie VincentCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Andreas M GrabruckerDepartment of Biological Sciences, University of Limerick, Limerick V94 T9PX, Ireland; Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
Christèle DubourgLaboratoire de Génétique Moléculaire & Génomique, CHU de Rennes, 35033 Rennes, France.
Undiagnosed Diseases Network
Wen-Hann TanDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nienke E VerbeekDepartment of Genetics, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands.
Martin GranzowInstitute of Human Genetics, University Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Gijs W E SantenDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, the Netherlands.
Jay ShendureDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Bertrand IsidorCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Laurent PasquierCHU Rennes, Service de Génétique Clinique, CNRS UMR6290, Université Rennes1, 35203 Rennes, France.
Richard RedonINSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France; CHU Nantes, l'institut du thorax, 44093 Nantes, France.
Yaping YangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77030, USA.
Matthew W StateDepartment of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Tjitske KleefstraDepartment of Human Genetics, Nijmegen Center for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, the Netherlands.
Benjamin CognéCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
GEM HUGORéseau de génétique et génomique médicale - Hôpitaux Universitaires du Grand Ouest, CHU Rennes, Service de Génétique Clinique, 35203 Rennes, France.
Deciphering Developmental Disorders StudyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
Slavé PetrovskiDepartment of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, VIC 3010, Australia.
Kyle RettererGeneDx, Gaithersburg, MD 20877, USA.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Pankaj B AgrawalDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Gene Discovery Core, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Stéphane BézieauCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France; CRCINA, Inserm, Université d'Angers, Université de Nantes, 44000 Nantes, France.
Sylvie OdentCHU Rennes, Service de Génétique Clinique, CNRS UMR6290, Université Rennes1, 35203 Rennes, France.
Ype ElgersmaDepartment of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands. Electronic address: y.elgersma@erasmusmc.nl.
Sandra MercierCHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France.
Génétique Médicale & Génomique Fonctionelle · FRBoston Children's Hospital · USChildren's Hospital of Philadelphia · USTelemark Hospital · NOBaylor College of Medicine · USErasmus MC · NLHeidelberg University · DEInserm · FRUniversity of Washington · USCentre Hospitalier Universitaire de Rennes · FRCentre National de la Recherche Scientifique · FRHarvard University · USLeiden University Medical Center · NLRadboud University Nijmegen · NLUniversity Medical Center Utrecht · NLArkansas Children's Hospital · USHospices Civils de Lyon · FRSeattle Children's Hospital · USStanford University · USUniversity of California, San Francisco · US
Funding
Sporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2MGenome Sequence-Based Screening for Childhood Risk and Newborn IllnessU19HD077671 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI BEGGS, ALAN H., GREEN, ROBERT C. · 2013 to 2018
$6.1MSPEG is Critical in Skeletal Muscle Development and FunctionR01AR068429 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI AGRAWAL, PANKAJ B · 2015 to 2019
$1.9MGenes and pathways underlying brain overgrowth and focal cortical malformationsK08NS092898 · NINDS · SEATTLE CHILDREN'S HOSPITAL · PI MIRZAA, GHAYDA · 2015 to 2019
$930kNIAMS NIH HHS R01 AR068429NICHD NIH HHS U19 HD077671NIMH NIH HHS R01 MH101221NINDS NIH HHS K08 NS092898
Abstract
Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.
Indexed as
AnimalsBrainCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell LineExomeFemaleGlutamic AcidHEK293 CellsHumansIntellectual DisabilityMaleMiceMice, Inbred C57BLMutationNeuronsPhosphorylationCalcium-Calmodulin-Dependent Protein Kinase Type 2CAMK2A protein, humanCAMK2B protein, humanGlutamic AcidAMPARCAMK2CAMK2ACAMK2Bde novo mutationsintellectual disabilityNMDARsynaptic plasticity
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
NCT02450851ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.