"A de novo missense variant in the MAST1 gene with a CADD score of 26.9 was identified in a male patient from the Solve-RD resource with the HPO phenoterm ""Autism"" in Laurie et al., 2025. Two de novo loss-of-function variants and seven de novo missense variants (2 with CADD >25) in this gene have been reported in ASD probands from the Autism Sequencing Consortium and the SPARK and MSSNG cohorts (Lim et al., 2017; Zhou et al., 2022; Fu et al., 2022). In a report describing six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM; OMIM 618273), Tripathy et al., 2018 also described two individuals identified via GeneMatcher with de novo MAST1 missense variants and ASD with additional features (speech delay/absent speech, ID, hypotonia, and dysmorphic features) but without significant findings on brain imaging."
Molecular Function
This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses
