Relevance to Autism

A de novo deletion encompassing the ARHGEF9 gene was identified in a male patient presenting with mild-to-moderate autism, severe intellectual disability, and epilepsy; iPSC-derived neural progenitor cells from this patient showed a complete loss of CB expression and hyperactivation of mTORC1 signaling under basal conditions (Machado et al., 2016). A second de novo deletion involving the ARHGEF9 gene was identified in an 8-year-old female patient diagnosed with ASD and ADHD and presenting with mild intellectual disability, global developmental delay, and severe speech impairment (Bhat et al., 2016). A phenotypic review of 18 patients with ARHGEF9 variants (10 previously published, 8 novel; 13 males, 5 females with highly skewed X-chromosome inactivation) demonstrated that the majority of patients presented with intellectual disability, epilepsy, and dysmorphic facial features; 4 of the 18 patients described in this report presented with autistic features (Alber et al., 2017).

Molecular Function

The protein encoded by this gene is a Rho-like GTPase that acts as a guanine nucleotide exchange factor (GEF) for CDC42 and other genes and promotes the formation of GPHN clusters. Variants in this gene are associated with a form of early infantile epileptic encephalopathy (EIEE8, OMIM 300607).

External Links

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