ArticleMolecular psychiatry2012
SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism.
Article in Molecular psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 4 of them syntheses that pooled it.
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Who cites it
185 citing papers in PubMed, 4 syntheses or guidelines pooled it, 316 citations in OpenAlex.
- Pooled it
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
- Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.PLoS genetics · 2014Pooled it
- Glutamatergic candidate genes in autism spectrum disorder: an overview.Journal of neural transmission (Vienna, Austria : 1996) · 2014Pooled it
- Peripheral blood mononuclear cell proteomic profiling reveals cytoskeletal- and chromatin-associated protein signatures in autism spectrum disorder.Brain, behavior, & immunity - health · 2026Article
- Review
- Characterization of Electrophysiological and Transcriptomic Alterations in Patient-Derived Neurons from CHAMP1 Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Nitric oxide inhibition ameliorates cortical proteomic changes in the Cntnap2Molecular autism · 2026Article
- SHANK3 and beta-synuclein are novel blood-based biomarkers for the Phelan-McDermid Syndrome: a pilot study.Translational psychiatry · 2026Article
- Patient-derived brain organoids reveal divergent neuronal activity across subpopulations of autism spectrum disorder.Translational psychiatry · 2026Article
- Disrupted cortex-wide dynamics impair motor planning in Shank3-mutant mice.bioRxiv : the preprint server for biology · 2026Article
- A spatial transcriptomic atlas of autism-associated genes identifies convergence in the developing human thalamus.bioRxiv : the preprint server for biology · 2025Article
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Disrupted transcriptional networks regulated by CHD1L during neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant.Nucleic acids research · 2025Article
- Male caregiving experience alters hippocampal neuroplasticity and transcription independent of reproduction in a biparental species.Communications biology · 2025Article
- Neuroplasticity-Based Approaches to Sensory Processing Alterations in Autism Spectrum Disorder.International journal of molecular sciences · 2025Review
- SHANK2 establishes auditory hair bundle architecture essential for mammalian hearing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior.Nature communications · 2025Article
- The multifaceted role of mitochondria in autism spectrum disorder.Molecular psychiatry · 2025Review
- Case Report: Co-occurringFrontiers in genetics · 2025Article
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies.
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