De novo missense variants in the MAST3 gene have been identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the MSSNG cohort (Yuen et al., 2017). Shu et al., 2021 reported 11 individuals with de novo missense variants in the STK domain of the MAST3 gene presenting with developmental and epileptic encephalopathy (DEE) ; six of these patients also presented with ASD or autistic features, while a seventh patient also presented with stereotypy. Subsequent functional analysis of MAST3 missense variants in this report demonstrated variable but generally lower expression with concomitant increased phosphorylation of the MAST3 target ARPP-16 compared to wild-type, suggesting gain-of-function effects. Shu et al., 2022 reported four additional individuals with de novo MAST3 missense variants; two of these patients were diagnosed with ASD by ABC and CARS. Additional analysis of published large-scale exome sequencing data in this report demonstrated an excess of missense variants in the DUF domain of MAST3 in ASD cohorts, as well as an excess of missense variants in the STK domain in DEE cohorts, when compared with gnomAD.
Molecular Function
Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization; intracellular signal transduction; and peptidyl-serine phosphorylation. MAST3 has been shown to interact with the ASD-associated gene PTEN (Valiente et al., 2005).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy
