Evidence map›Paper›PMID 41125872›Full record

ArticleNature genetics2025

Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.

Reza Asadollahi, Aisha Ahmad, Paranchai Boonsawat, Jasmine Shahanoor Hinzen, Mareike Lohse, Boris Bouazza-Arostegui, Siqi Sun, Tillmann Utesch, Jonas D Sommer, Dragana Ilic and 140 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
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

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Munc13-1 couples DAG and CaScience advances · 2026
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

150 authors.

Reza AsadollahiInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland. R.Asadollahi@greenwich.ac.uk.ORCID http://orcid.org/0000-0002-1497-0564
Aisha AhmadDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Paranchai BoonsawatInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Jasmine Shahanoor HinzenDepartment of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Mareike LohseDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID http://orcid.org/0009-0001-5149-7833
Boris Bouazza-ArosteguiInstitute of Neurophysiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-8278-5259
Siqi SunLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0009-0002-8291-3358
Tillmann UteschLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0000-0002-3617-2002
Jonas D SommerLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Dragana IlicLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Murugesh PadmanarayanaDepartment of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Kati FischermannsLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Mrinalini RanjanDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Moritz BollLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Chandran KaUniv Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.
Amélie PitonInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.ORCID http://orcid.org/0000-0003-0408-7468
Francesca MattioliInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Bertrand IsidorNantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.
Katrin ÕunapGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.ORCID http://orcid.org/0000-0002-4594-6364
Karit ReinsonGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
Monica H WojcikDivisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8162-5031
Christian R MarshallGenome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-4003-7671
Saadet Mercimek-AndrewsDepartment of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.ORCID http://orcid.org/0000-0001-9846-6500
Noriko MiyakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.ORCID http://orcid.org/0000-0001-5322-2983
Bruno de Oliveira StephanClinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Rachel Sayuri HonjoClinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Debora R BertolaClinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Chong Ae KimClinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.ORCID http://orcid.org/0000-0002-1754-1300
Roman YusupovDivision of Clinical Genetics, Joe DiMaggio Children's Hospital, Hollywood, FL, USA.
Heather C MeffordCenter for Pediatric Neurological Disease Research, St. Jude Children's Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-7188-522X
John ChristodoulouBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-8431-0641
Joy LeeDepartment of Metabolic Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-6158-6215
Oliver HeathVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0003-4191-3319
Natasha J BrownDepartment of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Naomi BakerVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Zornitza StarkDepartment of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-8640-1371
Martin DelatyckiVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Nicole J LakeBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0003-4103-6387
Shimriet ZeidlerDepartment of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8597-2359
Linda ZuurbierAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam, The Netherlands.
Saskia M MaasAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam, The Netherlands.
Chris C de KruiffEmma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands.ORCID http://orcid.org/0009-0006-4104-284X
Farrah RajabiDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Lance H RodanDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Stephanie A CouryDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.ORCID http://orcid.org/0000-0001-6127-6308
Henry OppermannInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Rami Abou JamraInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.ORCID http://orcid.org/0000-0002-1542-1399
Skadi BebloCenter for Pediatric Research, University Hospital for Children and Adolescents, and Centre for Rare Diseases, University Hospital Leipzig, Leipzig, Germany.
Caroline MaxtonZentrum für Kinderneurologie, Hamburg, Germany.
Robert ŚmigielDepartment of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Medical University of Wrocław, Wrocław, Poland.ORCID http://orcid.org/0000-0003-2930-9549
Hunter UnderhillDepartment of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA.
Holly DubbsDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Alyssa RosenDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Katherine L HelbigDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8249-0549
Ingo HelbigDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8486-0558
Sarah McKeown RuggieroDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mark P FitzgeraldDivision of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7121-0705
Dennis KraemerInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Carlos E PradaDivision of Genetics and Rare Diseases, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-3348-3531
Jeffrey TenneyDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Parul JayakarDivision of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA.
Sylvia RedonUniv Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.ORCID http://orcid.org/0000-0001-7310-1142
Jérémie LefrancPediatrics Department, Competence Center for Epilepsy, Hôpital Morvan, CHU Brest, Brest, France.
Kevin UguenUniv Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.
Simone RaceDivision of Biochemical Genetics, BC Children's Hospital, Vancouver, British Columbia, Canada.
Stephanie EfthymiouDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0003-4900-9877
Reza MaroofianDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0001-6763-1542
Henry HouldenDepartment of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0002-2866-7777
Sandra CoppensCenter of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.
Nicolas DeconinckCentre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium.
Balasubramaniem AshokkumarSchool of Biotechnology, Madurai Kamaraj University, Madurai, India.ORCID http://orcid.org/0000-0003-2213-5400
Perumal VaralakshmiSchool of Biotechnology, Madurai Kamaraj University, Madurai, India.ORCID http://orcid.org/0000-0002-5420-4688
Vykunta Raju Gowda KIndira Gandhi Institute of Child Health, Bangalore, India.
Fatemeh EghbalDepartment of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.
Ehsan Ghayoor KarimianiDepartment of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.
Morteza HeidariMyelin Disorders Clinic, Department of Pediatric Neurology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
John NeidhardtHuman Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.ORCID http://orcid.org/0000-0002-9205-8394
Marta Owczarek-LipskaHuman Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.
G Christoph KorenkeDepartment of Neuropediatrics, University Children's Hospital, Klinikum Oldenburg, Oldenburg, Germany.
Michael J BamshadDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Philippe M CampeauDepartment of Pediatrics, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-9713-7107
Anna LehmanDepartment of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada.
Laura G HendonDepartment of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
Ingrid M WentzensenGeneDx, LLC, Gaithersburg, MD, USA.
Kristin G MonaghanGeneDx, LLC, Gaithersburg, MD, USA.
Yanmin ChenGeneDx, LLC, Gaithersburg, MD, USA.
Anna SzutoThe Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-9140-6193
Ronald D CohnThe Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-6775-1496
Ping Yee Billie AuDepartment of Medical Genetics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.ORCID http://orcid.org/0000-0002-9533-7217
Christoph HübnerDepartment of Neuropediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Felix BoschannInstitut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Kandamurugu ManickamDivision of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Daniel C KoboldtDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
Aboulfazl RadArcensus GmbH, Rostock, Germany.ORCID http://orcid.org/0000-0001-8627-8828
Gabriela OpreaArcensus GmbH, Rostock, Germany.ORCID http://orcid.org/0000-0001-5467-5247
Kristine K BachmanDepartment of Pediatrics, Women's and Children's Institute, Geisinger Medical Center, Danville, PA, USA.
Andrea H SeeleyDepartment of Pediatrics, Women's and Children's Institute, Geisinger Medical Center, Danville, PA, USA.
Emanuele AgoliniLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.ORCID http://orcid.org/0000-0001-6543-6225
Alessandra TerraccianoLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.ORCID http://orcid.org/0000-0001-9748-3982
Piscopo CarmeloMedical and Laboratory Genetics Unit, A.O.R.N. "Antonio Cardarelli", Naples, Italy.
Caleb BuppCorewell Health West Helen DeVos Children's Hospital, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0003-4255-0396
Bethany GryskoCorewell Health West Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
Annick Rein-RothschildThe Institute for Rare Diseases, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Bruria Ben ZeevSchool of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Amy MargolinDivision of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA.ORCID http://orcid.org/0000-0003-4332-9693
Jennifer MorrisonDivision of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA.
Aditi DagliDivision of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA.
Elliot StolermanGreenwood Genetic Center, Greenwood, SC, USA.
Raymond J LouieGreenwood Genetic Center, Greenwood, SC, USA.
Camerun WashingtonGreenwood Genetic Center, Greenwood, SC, USA.
Servi J C StevensDepartment of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.ORCID http://orcid.org/0000-0001-8769-3150
Malou HeijligersDepartment of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.ORCID http://orcid.org/0000-0002-0174-8278
Fowzan S AlkurayaDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID http://orcid.org/0000-0003-4158-341X
Jasmin LisfeldInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Axel NeuDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Fabíola Paoli MonteiroMedical Department, Mendelics Genomic Analysis, São Paulo, Brazil.
André Luiz Santos PessoaFederal University of Ceará - UFC and Hospital Infantil Albert Sabin, Fortaleza, Brazil.
Antonio Edvan Camelo-FilhoFederal University of Ceará - UFC and Hospital Infantil Albert Sabin, Fortaleza, Brazil.ORCID http://orcid.org/0000-0002-1213-1687
Fernando KokDepartment of Neurology, Neurogenetics Center, University of São Paulo, São Paulo, Brazil.
Dwight KoeberlDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Kacie RileyDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Lydie BurglenDépartement de Génétique, Centre de référence des malformations et maladies congénitales du cervelet, Hôpital Trousseau, AP-HP.Sorbonne Université, Paris, France.ORCID http://orcid.org/0000-0002-1119-6809
Diane DoummarService de Neuropédiatrie-Pathologie du Développement, Centre de Référence Neurogénétique, Hôpital Trousseau, FHU I2-D2, AP-HP.Sorbonne Université, Paris, France.
Bénédicte HéronService de Neuropédiatrie-Pathologie du Développement, Centre de Référence Neurogénétique, Hôpital Trousseau, FHU I2-D2, AP-HP.Sorbonne Université, Paris, France.
Cyril MignotDépartement de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France.
Boris KerenDépartement de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France.
Perrine CharlesDépartement de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France.
Caroline NavaDépartement de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France.ORCID http://orcid.org/0000-0003-1272-0518
Felix P BernhardDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Andrea A KühnMovement Disorders and Neuromodulation Unit, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Sven ThomsBiochemistry and Molecular Medicine, Medical School OWL, Bielefeld University, Bielefeld, Germany.ORCID http://orcid.org/0000-0003-3018-6363
Ryan D MorrieTrace Neuroscience, South San Francisco, CA, USA.
Shila MekhoubadTrace Neuroscience, South San Francisco, CA, USA.
Eric M GreenTrace Neuroscience, South San Francisco, CA, USA.
Sami J BarmadaUniversity of Michigan School of Medicine, Ann Arbor, MI, USA.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8603-1526
Olaf JahnNeuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID http://orcid.org/0000-0002-3397-8924
Jeong Seop RheeDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Christian RosenmundInstitute of Neurophysiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Mišo MitkovskiCity Campus Light Microscopy Facility, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID http://orcid.org/0000-0001-9195-2434
Heinrich StichtInstitute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.ORCID http://orcid.org/0000-0001-5644-045X
Han SunLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0000-0002-1655-0838
Gerald Le GacUniv Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.
Holger TaschenbergerDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID http://orcid.org/0000-0003-3186-3231
Nils BroseDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID http://orcid.org/0000-0003-0938-8534
Jeremy S DittmanDepartment of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Anita RauchInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-2930-3163
Noa LipsteinDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. Lipstein@FMP-berlin.de.ORCID http://orcid.org/0000-0002-0755-5899

Funding

Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ana Marie Daugherty · 2021 to 2026
$26.5M
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Broad Institute Mendelian Genomic Research CenterU01HG011755 · NHGRI · BROAD INSTITUTE, INC. · PI Anne O'Donnell-Luria, MICHAEL E TALKOWSKI · 2021 to 2026
$14.6M
NHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9M
RNA decay in amyotrophic lateral sclerosis and frontotemporal lobar degenerationR01NS097542 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2016 to 2025
$3.8M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
A computational phenotyping approach to characterize neurogenetic disordersR01NS131512 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Ingo Helbig · 2023 to 2026
$2.8M
Subgroup delineation in genetic epilepsies and developmental brain disordersR01NS127830 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Ingo Helbig · 2023 to 2026
$2.8M
Analysis of Synaptic Protein DynamicsR01NS116747 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Jeremy Samuel Dittman · 2020 to 2026
$2.6M
Atypical TDP43 isoforrms driving neurodegeneration in FTD/ALSR01NS113943 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2020 to 2024
$1.9M
Joint analysis of genomic and electronic medical record data to assess outcomes and drug response in pediatric epilepsiesK02NS112600 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI HELBIG, INGO · 2020 to 2024
$963k
Department of Health | National Health and Medical Research Council (NHMRC) GNT1113531Deutsche Forschungsgemeinschaft (German Research Foundation) 424778381 - TRR 295Deutsche Forschungsgemeinschaft (German Research Foundation) CRC 1286Deutsche Forschungsgemeinschaft (German Research Foundation) CRC 1286 Project A9Deutsche Forschungsgemeinschaft (German Research Foundation) EXC-2049-390688087Deutsche Forschungsgemeinschaft (German Research Foundation) EXC2067/1-390729940Deutsche Forschungsgemeinschaft (German Research Foundation) HE5415/3-1Deutsche Forschungsgemeinschaft (German Research Foundation) HE5415/5-1Deutsche Forschungsgemeinschaft (German Research Foundation) HE5415/6-1Deutsche Forschungsgemeinschaft (German Research Foundation) He5415/7-1Deutsche Forschungsgemeinschaft (German Research Foundation) NE 2118/2-1Deutsche Forschungsgemeinschaft (German Research Foundation) NE 2118/3-1Deutsche Forschungsgemeinschaft (German Research Foundation) TH1538/3-1EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC Advanced Grant SynPrimeEesti Teadusagentuur (Estonian Research Council) PRG2040Eesti Teadusagentuur (Estonian Research Council) PRG471Einstein Stiftung Berlin (Einstein Foundation Berlin) EZ-2014-226Indian Council of Medical Research (ICMR) INDO/FRC/452/(Y-83)/2016-17/IHDJapan Agency for Medical Research and Development (AMED) JP24ek0109548Japan Agency for Medical Research and Development (AMED) JP24ek0109617Japan Agency for Medical Research and Development (AMED) JP24ek0109674Japan Agency for Medical Research and Development (AMED) JP24ek0109677Japan Agency for Medical Research and Development (AMED) JP24ek0109760NHGRI NIH HHS R01 HG009141NHGRI NIH HHS U01 HG011755NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006493NHGRI NIH HHS UM1 HG008900NIA NIH HHS P30 AG072931NIH HHS S10 OD021553NINDS NIH HHS F31 NS130894NINDS NIH HHS K02 NS112600NINDS NIH HHS R01 NS097542NINDS NIH HHS R01 NS113943NINDS NIH HHS R01 NS116747NINDS NIH HHS R01 NS127830NINDS NIH HHS R01 NS131512RCUK | Medical Research Council (MRC) (ICGNMD) MR/S005021/1RCUK | Medical Research Council (MRC) UK MR/J004758/1, G0802760, G1001253 and (ICGNMD) MR/S005021/1State Government of Victoria (Victorian Government) Operational Infrastructure Support ProgramTarget ALS (Target ALS Foundation) IL-2023-C1-L2U.S. Department of Health & Human Services | National Institutes of Health (NIH) NS 116747U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG009141U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) U01HG011755U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG008900U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01 NS127830-01A1U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) S10OD021553Wellcome TrustWellcome Trust (Wellcome) strategic awards (Synaptopathies) (WT093205MA and WT104033/Z/14/Z)
6 · The paper itself

Abstract

The UNC13A gene encodes a presynaptic protein that is crucial for setting the strength and dynamics of information transfer between neurons. Here we describe a neurodevelopmental syndrome caused by germline coding or splice-site variants in UNC13A. The syndrome presents with variable degrees of developmental delay and intellectual disability, seizures of different types, tremor and dyskinetic movements and, in some cases, death in early childhood. Using assays with expression of UNC13A variants in mouse hippocampal neurons and in Caenorhabditis elegans, we identify three mechanisms of pathogenicity, including reduction in synaptic strength caused by reduced UNC13A protein expression, increased neurotransmission caused by UNC13A gain-of-function and impaired regulation of neurotransmission by second messenger signalling. Based on a strong genotype-phenotype-functional correlation, we classify three UNC13A syndrome subtypes (types A-C). We conclude that the precise regulation of neurotransmitter release by UNC13A is critical for human nervous system function.

Indexed as

Nerve Tissue ProteinsNeurodevelopmental DisordersSynapsesAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsFemaleHippocampusHumansIntellectual DisabilityMaleMiceNeuronsSynaptic TransmissionSyndromeCaenorhabditis elegans ProteinsNerve Tissue Proteins

Identifiers

PMID41125872
PMCPMC12597829

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