Relevance to Autism

Missense variants in the PPP2R1A gene have been identified in ASD probands from the Autism Sequencing Consortium and, more recently, from a cohort of 75 Turkish patients diagnosed with ASD (Satterstrom et al., 2020; Marques et al., 2022; Fu et al., 2022; Kayhan et al., 2026), while de novo coding-synonymous variants in this gene were previously reported in ASD probands from the MSSNG cohort (Yuen et al., 2017). Lenaerts et al., 2021 described 30 individuals with 16 different PPP2R1A variants presenting with a variable neurodevelopmental disorder characterized by developmental delay with language delay, hypotonia, behavioral problems (including ASD or autistic features in 6 individuals), dysmorphic features, joint hypermobility, and hypoplasia/agenesis of the corpus callosum. Subsequent functional assessment of a subset of disease-associated variants of Lenarets et al., 2021 demonstrated altered PP2A B-type subunit binding, altered C subunit binding, and/or impaired overall PP2A activity, while the ASD-associated p.Ser152Phe variant was shown to cause a reduction in dendritic spine number following expression in hippocampal neurons.

Molecular Function

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Heterozygous variants in this gene are responsible for Houge-Janssens syndrome 2 (OMIM 616362).

External Links

References