ArticlePLoS genetics2012
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 4 of them syntheses that pooled it.
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Who cites it
220 citing papers in PubMed, 4 syntheses or guidelines pooled it, 442 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
- Glutamatergic candidate genes in autism spectrum disorder: an overview.Journal of neural transmission (Vienna, Austria : 1996) · 2014Pooled it
- Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.PLoS genetics · 2014Pooled it
- Prenatal Folinic Acid in FRAA-Positive Pregnancies: Preschool Neurodevelopmental Outcomes from a Pilot RCT Follow-Up.Nutrients · 2026Trial
- Rare Functional Variants Associated with Antidepressant Remission in Mexican-Americans: Short title: Antidepressant remission and pharmacogenetics in Mexican-Americans.Journal of affective disorders · 2021Trial
- scMEDAL: interpretable single-cell transcriptomics analysis with batch effect visualization via deep mixed-effects autoencoder.Nature communications · 2026Article
- Co-occurrence of rare variants implicates gene pairs in cytoskeletal pathways and is associated with increased severity in autism spectrum disorder.Genome biology · 2026Article
- Development of an automated approach for investigating social learning in mice.Frontiers in behavioral neuroscience · 2026Article
- Hypersynchronous iPSC-derived SHANK2 neuronal networks are rescued by mGluR5 agonism.Stem cell reports · 2025Article
- Selection signatures detection in Nelore, Gir, and Red Sindhi cattle breeds.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Pre-existing DNA methylation signatures in the prefrontal cortex of alcohol-naïve nonhuman primates define neural vulnerability for future risky ethanol consumption.Neurobiology of disease · 2025Article
- Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns.Journal of neurodevelopmental disorders · 2025Article
- Overexpression of SHANK2 contributes malignant outcomes as a Hippo pathway regulator in gastric cancer.American journal of cancer research · 2025Article
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Autism patient-derived SHANK2BMolecular psychiatry · 2024Article
- Differential effectiveness of dietary zinc supplementation with autism-related behaviours inPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans.Molecular psychiatry · 2024Article
- Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology.Nature communications · 2024Article
- Functional Classification and Interaction Selectivity Landscape of the Human SH3 Domain Superfamily.Cells · 2024Article
160 more citing papers are in PubMed but not listed here.
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Authors and funding
60 authors at 20 institutions in 9 countries.
Funding
Abstract
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.
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Registered trials
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.