ArticleCell reports2014
CC2D1A regulates human intellectual and social function as well as NF-κB signaling homeostasis.
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Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 78 citations in OpenAlex.
- Interactome Analysis of the CC2D1A Scaffold Reveals Novel Neuronal Interactions and a Postsynaptic Role.Molecular & cellular proteomics : MCP · 2026Article
- Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes.Scientific reports · 2026Article
- Characterization, expression, and mutational analysis of endosomal protein lethal giant disc (Lgd/CC2D1A) as a biomarker in patients with T-cell acute lymphoblastic leukemia.Discover oncology · 2025Article
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Computational Analysis ofACS chemical neuroscience · 2025Article
- Linking autism risk genes to morphological and pharmaceutical screening by high-content imaging: Future directions and opinion.Psychiatry and clinical neurosciences · 2025Review
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- Comprehensive proteome profiling of molecular endotypes in Japanese adults with moderate-to-severe atopic dermatitis.Frontiers in medicine · 2025Article
- Endosomes serve as signaling platforms for RIG-I ubiquitination and activation.Science advances · 2024Article
- CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow.Life science alliance · 2024Article
- Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- CaMKIV-Mediated Phosphorylation Inactivates Freud-1/CC2D1A Repression for Calcium-Dependent 5-HT1A Receptor Gene Induction.International journal of molecular sciences · 2024Article
- A nonsenseHeliyon · 2024Article
- Article
- Identification of a Novel Variant in CC2D1A Gene Linked to Autosomal Recessive Intellectual Disability 3 in an Iranian Family and Investigating the Structure and Pleiotropic Effects of this Gene.Iranian journal of child neurology · 2024Article
- Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models.Oxford open neuroscience · 2024Article
- The Warburg micro syndrome protein RAB3GAP1 modulates neuronal morphogenesis and interacts with axon elongation end ER-Golgi trafficking factors.Neurobiology of disease · 2023Article
- UsingInternational journal of molecular sciences · 2022Article
- Genomics, convergent neuroscience and progress in understanding autism spectrum disorder.Nature reviews. Neuroscience · 2022Review
- Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking.Biomolecules · 2022Review
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Authors and funding
21 authors at 9 institutions in 4 countries.
M Chiara ManziniDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Lan XiongDepartment of Psychiatry, Research Centre of Montreal Mental Health University Institute, University of Montreal, Montreal, QC H1N 3V2, Canada; University of Montreal Hospital Research Centre, Montreal, QC H2L 2W5, Canada.
Ranad ShaheenDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Dimira E TambunanDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Stefania Di CostanzoDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Vanessa MitisalisDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
David J TischfieldDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Antonella CinquinoDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Mohammed GhaziuddinDepartment of Child and Adolescent Psychiatry, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Mehtab ChristianUniversity of Montreal Hospital Research Centre, Montreal, QC H2L 2W5, Canada.
Qin JiangDepartment of Psychiatry, Research Centre of Montreal Mental Health University Institute, University of Montreal, Montreal, QC H1N 3V2, Canada.
Sandra LaurentUniversity of Montreal Hospital Research Centre, Montreal, QC H2L 2W5, Canada.
Zohair A NanjianiMa Ayesha Memorial Centre, University of Karachi, Karachi 75350, Pakistan.
Saima RasheedAutism Institute, Karachi 74000, Pakistan.
R Sean HillDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Sofia B LizarragaDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Danielle GleasonDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Diya SabbaghDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Mustafa A SalihDivision of Pediatric Neurology, Department of Pediatrics, King Saud University College of Medicine, Riyadh 11461, Saudi Arabia. Electronic address: mustafa_salih05@yahoo.com.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. Electronic address: falkuraya@kfshrc.edu.sa.
Christopher A WalshDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: christopher.walsh@childrens.harvard.edu.
Boston Children's Hospital · USUniversité de Montréal · CAHarvard University · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USHoward Hughes Medical Institute · USKing Faisal Specialist Hospital & Research Centre · SAKing Saud University · SAUniversity of Karachi · PKUniversity of Michigan–Ann Arbor · US
Funding
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2MCell Identity Determination In Human Brain: Somatic Mutation and Cell LineageR01NS032457 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI Alice Eunjung Lee, Christopher A. Walsh · 1995 to 2026
$12.7MHUMAN EPILEPSY GENETICS--NEURONAL MIGRATION DISORDERSR01NS035129 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WALSH, CHRISTOPHER A. · 1997 to 2023
$9.5MFinding Autism Genes by Genomic Copy Number AnalysisR01MH083565 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI WALSH, CHRISTOPHER A. · 2007 to 2016
$6.9MIntracellular signaling in the development of human cognitive functionR00HD067379 · NICHD · GEORGE WASHINGTON UNIVERSITY · PI MANZINI, M. CHIARA · 2013 to 2015
$702kIntracellular signaling in the development of human cognitive functionK99HD067379 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI MANZINI, M. CHIARA · 2011 to 2012
$178kHoward Hughes Medical InstituteNICHD NIH HHS K99 HD067379NICHD NIH HHS P30 HD018655NICHD NIH HHS R00 HD067379NICHD NIH HHS R00HD067379NIMH NIH HHS R01 MH083565NIMH NIH HHS R01MH083565NINDS NIH HHS R01 NS032457NINDS NIH HHS R01NS032457NINDS NIH HHS R01 NS035129
Abstract
Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons reduces dendritic complexity and increases NF-κB activity, and the effects of Cc2d1a depletion can be rescued by inhibiting NF-κB activity. Homeostatic regulation of neuronal signaling pathways provides a mechanism whereby common founder mutations could manifest diverse symptoms in different patients.
Indexed as
AnimalsCells, CulturedChild Development Disorders, PervasiveDNA-Binding ProteinsHomeostasisHumansIntellectual DisabilityMiceMutationNeuronsNF-kappa BPedigreeRepressor ProteinsSeizuresSignal TransductionCC2D1A protein, humanCc2d1a protein, mouseDNA-Binding ProteinsNF-kappa BRepressor Proteins
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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.