Relevance to Autism

Two de novo missense variants in the G3BP2 gene have been identified in ASD probands (a p.Leu209Pro missense variant in an ASD proband from the Simons Simplex Collection, and a p.Arg13Trp missense variant in the ASD proband from the Autism Sequencing Consortium) (Iossifov et al., 2014; Satterstrom et al., 2020), while a de novo splice-site variant in this gene was identified in an ASD proband from the MSSNG cohort (Yuen et al., 2017). Enrichment analysis for de novo protein-altering variants in 40,853 probands with neurodevelopmental disorders, including 9,228 individuals with a primary diagnosis of ASD, in Jia et al., 2022 demonstrated that G3BP2 showed an excess of de novo missense variants with a false discovery rate (FDR) less than or equal to 0.01; subsequent functional analysis of G3BP2 missense variants used in this analysis found that three missense variants, including the ASD-associated p.Leu209Pro and p.Arg13Trp missense variants, resulted in significantly fewer stress granule formations under stress conditions compared with wild-type in transfected G3BP2 KO HeLa cells.

Molecular Function

Enables RNA binding activity. Involved in positive regulation of stress granule assembly and protein homooligomerization. Located in cytoplasmic stress granule and cytosol.

External Links

References