De novo variants in the SH3RF1 gene, including a splice-site variant and an in-frame insertion variant, have been identified in ASD probands (Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020). Yao et al., 2022 found that the protein encoded by the SH3RF1 gene (called POSH in this report) interacted with PSD-95 (the protein encoded by the ASD candidate gene DLG4) and the proteins encoded by the SHANK2 and SHANK3 genes, and that these interactions were required for dendritic spine development; furthermore, SH3RF1 conditional knockout mice exhibited autism-like behaviors, deficits in learning and memory, and abnormal evoked NMDAR EPSCs and NMDAR-dependent plasticity.
Molecular Function
This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
