ArticleNature genetics2021
Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2021. 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 67 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Genetic aetiology of global developmental delay and intellectual disability in Africa: a scoping review.Frontiers in genetics · 2026Pooled it
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Collaborative Genomics for Dystonia in Central and Eastern Europe: Successes Achieved, New Frontiers Ahead.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Polygenic Contribution to Sensorineural Hearing Loss Implicates Novel Risk Loci and Convergence with Congenital Hearing Loss Genes.Journal of the Association for Research in Otolaryngology : JARO · 2026Article
- External mechanical force drives axonal cytoskeletal rearrangements.Current biology : CB · 2026Article
- A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex.Science (New York, N.Y.) · 2026Article
- Clinical characterization and structural modeling of a novel de novo SPTBN1 missense variant in a Chinese child.BMC pediatrics · 2026Article
- Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence.Biomolecules · 2026Article
- Structural and functional modifications of neuronal lipid rafts: implications for HIV-associated neurological disorders.Journal of neuroinflammation · 2026Article
- Region-resolved proteomic map of the human brain: functional interconnections and neurological implications.Signal transduction and targeted therapy · 2026Article
- International Mouse Phenotyping Consortium Portal: facilitating investigation of gene function and providing insights into human disease.Nucleic acids research · 2026Article
- Whole Genome Sequencing of Discordant Monozygotic Twins Reveals Regulatory Variants Associated With Nonsyndromic Orofacial Clefts.Human mutation · 2026Article
- De novo protein-coding gene variants in developmental stuttering.Molecular psychiatry · 2026Article
- Durable response to ALK inhibition in low-allele-frequencyFrontiers in oncology · 2026Article
- Lactylated SPTAN1 Accelerates Hepatocellular Carcinoma Progression by Promoting NOTCH1/HES1 Activation and Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- International Mouse Phenotyping Consortium: Investigating gene function and providing insights into human disease.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic markers of disease risk and psychotherapy response in anxiety disorders - a longitudinal analysis of the DNA methylome.Molecular psychiatry · 2025Article
- Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity.Nature communications · 2025Article
- Simultaneous RNA Sequencing and DNA Methylation Profiling Reveals Neural Mechanisms That Regulate Sensitive Period Behavioral Learning.Genes, brain, and behavior · 2025Article
- Single-Cell Transcriptomics Reveals Effects of Long-Term Contact Lens Wearing on the Human Corneal Epithelium.Investigative ophthalmology & visual science · 2025Article
7 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
76 authors at 20 institutions in 7 countries.
Margot A Cousin *Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. cousin.margot@mayo.edu.ORCID http://orcid.org/0000-0002-6119-9346
Blake A Creighton *Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-6574-376X
Keith A BreauDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rebecca C SpillmannDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Erin TortiGeneDx, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0001-5790-1051
Sruthi DontuDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Swarnendu TripathiBioinformatics Research and Development Laboratory, Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Deepa AjitDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Reginald J EdwardsDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-6545-288X
Simone AfriyieDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Julia C BayDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kathryn M HarperDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-6297-0032
Alvaro A BeltranNeuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-1421-3889
Lorena J MunozHuman Pluripotent Stem Cell Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Liset Falcon RodriguezDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael C StankewichDepartment of Pathology, Yale University, New Haven, CT, USA.
Richard E PersonGeneDx, Gaithersburg, MD, USA.
Yue SiGeneDx, Gaithersburg, MD, USA.
Elizabeth A NormandGeneDx, Gaithersburg, MD, USA.
Amy BlevinsGeneDx, Gaithersburg, MD, USA.
Alison S MayDepartment of Neurology, Columbia University, New York, NY, USA.
Louise BierInstitute for Genomic Medicine, Columbia University, New York, NY, USA.
Vimla AggarwalInstitute for Genomic Medicine, Columbia University, New York, NY, USA.
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Kirsten CremerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Jessica BeckerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Hartmut EngelsInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Stefan AretzInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Jennifer J MacKenzieMcMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0002-3374-8619
Eva BrilstraDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Koen L I van GassenDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Richard H van JaarsveldDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0001-5247-6965
Renske OegemaDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-7146-617X
Gretchen M ParsonsSpectrum Health Medical Genetics, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0001-6495-5541
Paul MarkSpectrum Health Medical Genetics, Grand Rapids, MI, USA.
Ingo HelbigDivision of Neurology, Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8486-0558
Sarah E McKeownDivision of Neurology, Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Robert StrattonGenetics, Driscoll Children's Hospital, Corpus Christi, TX, USA.
Benjamin CogneService de Génétique Médicale, CHU Nantes, Nantes, France.ORCID http://orcid.org/0000-0002-5503-6292
Bertrand IsidorService de Génétique Médicale, CHU Nantes, Nantes, France.
Pilar CacheiroWilliam Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-6335-8208
Damian SmedleyWilliam Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Helen V FirthDepartment of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK.
Tatjana BierhalsInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Katja KlothInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Deike WeissNeuropediatrics, Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cecilia FairleyDivision of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Joseph T ShiehDivision of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0746-6084
Amy KritzerDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Parul JayakarNicklaus Children's Hospital, Miami, FL, USA.
Evangeline Kurtz-NelsonDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Raphael A BernierDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Tianyun WangDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5179-087X
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8246-4014
Ingrid M B H van de LaarDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Allyn McConkie-RosellDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Marie T McDonaldDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Jennifer KemppainenCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Brendan C LanpherCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Laura E Schultz-RogersCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Lauren B GundersonCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Pavel N PichurinCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Grace YoonDivisions of Clinical/Metabolic Genetics and Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Michael ZechInstitute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Robert JechDepartment of Neurology, Charles University, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
Juliane WinkelmannInstitute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Undiagnosed Diseases Network
Genomics England Research Consortium
Adriana S BeltranHuman Pluripotent Stem Cell Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael T ZimmermannBioinformatics Research and Development Laboratory, Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0001-7073-0525
Brenda TempleDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sheryl S MoyDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Eric W KleeCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Queenie K-G TanDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Damaris N LorenzoDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. damaris_lorenzo@med.unc.edu.ORCID http://orcid.org/0000-0002-6856-2988
University of North Carolina at Chapel Hill · USMayo Clinic · USUniversity Medical Center Utrecht · NLUniversity of Bonn · DEColumbia University · USDuke Medical Center · USErasmus MC · NLUniversität Hamburg · DEUniversity of Washington · USCentre National de la Recherche Scientifique · FRChildren's Hospital of Philadelphia · USHelmholtz Zentrum München · DEQueen Mary University of London · GBSpectrum Health · USUniversity of California, San Francisco · USBoston Children's Hospital · USCambridge University Hospitals NHS Foundation Trust · GBCharles University · CZDriscoll Children's Hospital · USHoward Hughes Medical Institute · US
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5MAn integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4MUNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5MPreclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7MSporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2MPreclinical CoreU54HD079124 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BELGER, AYSENIL · 2013 to 2019
$8.0MRole of Ankyrin-B in the Nervous SystemR01NS110810 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LORENZO, DAMARIS N · 2020 to 2024
$1.9MCancer Research UKDepartment of HealthHoward Hughes Medical InstituteMedical Research CouncilNCI NIH HHS P30 CA016086NHGRI NIH HHS U01 HG007672NICHD NIH HHS P50 HD103573NICHD NIH HHS U54 HD079124NIMH NIH HHS R01 MH101221NINDS NIH HHS P30 NS045892NINDS NIH HHS R01 NS110810
Abstract
SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system.
Indexed as
Genes, DominantGenetic Predisposition to DiseaseGenetic VariationAnimalsGenetic Association StudiesHeterozygoteHumansMiceNeurodevelopmental DisordersPhenotypeSpectrinSpectrinSPTBN1 protein, human
Identifiers
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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.