Relevance to Autism

A number of de novo variants in the MTSS2 gene, including a de novo loss-of-function (LoF) variant and several de novo missense variants, have been identified in ASD probands (Satterstrom et al., 2020; Zhou et al., 2022; Trost et al., 2022). Huang et al., 2022 described a cohort of five unrelated individuals with a recurrent de novo MTSS2 missense variant (c.2011C>T;p.Arg671Trp) presenting with a neurodevelopmental syndrome [Intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF); OMIM 620086] characterized by global developmental delay and/or mild intellectual disability, ophthalmological anomalies, distinctive facial features (upslanting palpebral fissures, epicanthus, and bitemporal narrowing), and microcephaly; autism spectrum disorder was diagnosed in two of the three individuals from this cohort who were old enough to be evaluated. Functional analysis of the recurrent p.Arg617Trp missense variant in Drosophila in Huang et al., 2022 demonstrated a partial loss-of-function effect and increased toxicity compared to wild-type MTSS2, suggesting that this variant may act as a dominant-negative allele. A female ASD proband from the SPARK cohort was also found to have the functionally validated de novo p.Arg617Trp missense variant (Zhou et al., 2022).

Molecular Function

Enables GTPase activator activity and small GTPase binding activity. Involved in activation of GTPase activity and cellular response to platelet-derived growth factor stimulus. Located in ruffle membrane.

External Links

References