Relevance to Autism

Chmielewska et al., 2021 reported six unrelated individuals with missense or protein-truncating variants in the PTPN4 gene who exhibited varying degrees of intellectual disability or developmental delay; two of these individuals presented with autism spectrum disorder, and the missense variant identified in one of these individuals with ASD (p.Gly239Arg in patient 1 in this report) was shown experimentally to result in failure of PTPN4 to localize to the dendritic spines of transfected rat hippocampal neurons, in contrast to WT PTPN4. Mutations in PTPN4 had previously been identifed in monozygotic twins presenting with a Rett syndrome-like phenotype characterized by developmental delay, seizures, and stereotypic hand movements (Williamson et al., 2015), as well as in a child presenting with developmental delay, autistic features, and upper limb stereotypies (Szczauba et al., 2018).

Molecular Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation.

External Links

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