Autism spectrum disorder (ASD) consists of a complex, broad range of phenotypes that may include challenges in speech, social skills and communication, repetitive behaviors, and intellectual disability. Globally, ASD affects approximately 1% of the population with a skewed sex ratio of 4:1 male versus female. ASD pathogenesis is not well understood and involves numerous genetic, environmental, and social factors. The genetics of ASD is highly complex, with both high-penetrance single gene mutations linked to syndromic autism and numerous risk variants implicated in idiopathic autism.

Genes consistently implicated in ASD can be grouped into categories with functional overlap and crosstalk. At the level of transcriptional regulation, ASD-linked variants can be found in major signalling pathways implicated in nervous system development including the Wnt, Hedgehog, retinoic acid, ERK/MAPK, and PI3K/mTOR pathways. ASD is also linked to activity-dependent transcriptional regulation downstream of calcium signalling (NFAT, MEF2, CREB, FOXO). Variants in epigenetic modifiers also impart ASD risk, particularly in DNA methylation (e.g., MeCP2, mutations in which cause Rett Syndrome) and chromatin structure (e.g., CHD8). Fragile X syndrome, characterized by ASD-like behaviours, is linked to translational repression of several ASD-linked and neuronal transcripts by FMR1. Variants in genes involved in synaptogenesis and synaptic function including neuroligins (NLGNs), neurexins (NRXNs), postsynaptic density scaffolds (e.g., SHANKs), and ion channels are also implicated in ASD pathogenesis.

BioGRID curators have initially focused on biological interaction curation for 134 genes that are strongly implicated in ASD through whole genome sequencing analysis (see Trost et al 2022, Genomic architecture of autism from comprehensive whole-genome sequence annotation, Cell 185:4409-4427.e18, PMCID10726699). Details on how these gene lists were generated are available in the methods section of this publication (see Supplementary Table S2D). The ASD project is being developed in collaboration with both experimental and computational groups using machine learning (ML)-based text analysis and will be expanded to include additional genes relevant to ASD. This project page allows users to query protein, genetic and chemical interactions, as well as post-translational modifications (PTMs), of the ASD gene network.

The ASD curation project is on-going and will be updated each month. If you notice errors or missing interactions/publications in this dataset, or otherwise wish to contribute to this project, please contact us at support@thebiogrid.org. All ASD-associated BioGRID records, including the entire dataset, are freely available for download from links within this project.