Protein interactome reveals converging molecular pathways among autism disorders
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We developed an autism protein interaction network that provides a framework for studying autism pathogenesis and reveals shared molecular pathways among distinct autism spectrum disorders.
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Systematic study has found hundreds of direct protein-protein interactions among products of ASD-implicated genes, including a network involving SHANK and TSC1.
“For example, systematic study has uncovered hundreds of direct protein-protein interactions amongst products of genes previously implicated in ASD, including a network involving SHANK and TSC1 (Sakai et al., 2011).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Sakai et al., 2011
The interactome uncovered several new interactions, including one between the ASD candidate genes Shank3 and TSC1.
“This interactome revealed several novel interactions, including between two ASD candidate genes, Shank3 and TSC1.”
From Genetics of autism spectrum disorders (2011) · cites this paper as [70]
A second study of molecular convergence in ASD identified proteins that interact with known ASD or ASD-associated genes.
“The second study on molecular convergence in ASD identified protein interactors of known ASD or ASD-associated genes [70].”
From Genetics of autism spectrum disorders (2011) · cites this paper as [70]
This study's biological pathways include synapse, cytoskeleton, and GTPase signaling, and they overlap remarkably with those found in the gene expression and CNV pathway studies discussed above.
“The biological pathways identified in this study include synapse, cytoskeleton, and GTPase signaling, demonstrating a remarkable overlap with those identified by the gene expression and CNV pathway studies discussed above.”
From Genetics of autism spectrum disorders (2011) · cites this paper as [70]
The PPI network seeded around those 35 genes was highly interconnected.
“showed that the PPI network seeded around these 35 genes was indeed highly interconnected.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [124]
A Y2H screen of 35 syndromic or candidate ASD genes identified many novel PPIs.
“Sakai and colleagues124 carried out a Y2H screen of 35 syndromic or candidate ASD genes and identified many novel PPIs.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [124]
Many studies of complex neuropsychiatric disorders have concluded that disease-causing variants are often clustered in protein-interaction networks with a high degree of connectivity among themselves and that these clustered networks are often enriched with functional pathways relevant to brain functions.
“Many studies of complex neuropsychiatric disorders have also concluded that disease-causing variants are often clustered in protein-interaction networks with a high degree of connectivity among themselves and that these clustered networks are often enriched with functional pathways relevant to brain functions [72–80].”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [77]
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- Authors
- Sakai, Y., Shaw, C. A., Dawson, B. C., Dugas, D. V., Al-Mohtaseb, Z., Hill, D. E., & Zoghbi, H. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Baylor College of Medicine (US)
- Harvard University (US)
- Corresponding author
- Shaw, Chad A.
- Zoghbi, Huda Y.
- Venue
- Science Translational Medicine
- Published
- 2011-06-08
- Volume
- 3
- Issue
- 86
- Pages
- 86ra49-86ra49
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC3169432
- OpenAlex
- W2126924893
- Cited by
- 226
- References
- 55
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 12 · 2018: 7 · 2017: 11 · 2016: 18 · 2015: 16 · 2014: 23 · 2013: 26 · 2012: 32
- FWCI
- 13.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Japan Society for the Promotion of Science (23810025)
- National Institute of Neurological Disorders and Stroke (R01NS057819)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- autism spectrum disorder, protein-protein interaction network, shank, TSC1, copy number variation, de novo deletion, Xq28 duplication, PKM2, filamin A, idiopathic autism, syndromic autism, molecular pathways
- MeSH terms
- Animals, Brain, Cell Line, Child Development Disorders, Pervasive, Humans, Infant, Newborn, Nerve Tissue Proteins, Two-Hybrid System Techniques, Protein Interaction Mapping, Immunoprecipitation, Mice
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