Quantitative proteomics and phosphoproteomics of PPP2R5D variants reveal deregulation of RPS6 phosphorylation through converging signaling cascades.

ABSTRACT: Variants in the phosphoprotein phosphatase-2 regulatory protein-5D gene ( PPP2R5D ) cause the clinical phenotype of Jordan's Syndrome (PPP2R5D-related disorder), which includes intellectual disability, hypotonia, seizures, macrocephaly, autism spectrum disorder and delayed motor skill development. The disorder originates from de novo single nucleotide mutations, generating missense variants that act in a dominant manner. Pathogenic mutations altering 13 different amino acids have been identified, with the E198K variant accounting for ∼40% of reported cases. Here, we use CRISPR-PRIME genomic editing to introduce a transition (c.592G>A) in the PPP2R5D allele in a heterozygous manner in HEK293 cells, generating E198K-heterozygous lines to complement existing E420K variant

SUBMITTER: Ka S 

PROVIDER: S-EPMC10081281 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature