Relevance to Autism

A number of de novo variants in the ARHGEF2 gene, including three potenitally deleterious de novo missense variants, have been identiified in ASD probands (De Rubeis et al., 2014; Yuen et al., 2017; Turner et al., 2017; Guo et al., 2019; Satterstrom et al., 2020). A de novo non-coding variant that was predicted to target the ARHGEF2 gene via chromatin interactions was identified in a Korean ASD proband from a simplex family in Kim et al., 2022; functional analysis in human induced pluripotent stem cells derived from the proband and the proband's parents demonstrated that this variant resulted in significantly reduced levels of ARHGEF2 expression in patient-derived hiPSCs compared to parent-derived hiPSCs.

Molecular Function

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Homozygous mutations in this gene are responsible for neurodevelopmental disorder with midbrain and hindbrain malformations (NEDMHM; OMIM 617523), a disorder characterized by intellectual disability and speech delay associated with mild microcephaly and midbrain-hindbrain malformations on brain imaging (Ravindran et al., 2017).

External Links

References