SHANK2

This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density (PSD). Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, an SH3 domain, a PSD-95/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain. An alternative hypothesis is that the Homer/Shank/GKAP/PSD-95 assembly mediates physical association of the NMDAR with IP3R/RYR and intracellular Ca2+ stores. == Interactions ==

SHANK2 has been shown to interact with: • ARHGEF7, • Cortactin, • DLG4, • DLGAP1, == Associations with neuropsychiatric disease ==

Mutations in SHANK2 have been associated with autism spectrum disorder (ASD) and schizophrenia. In particular, heterozygous loss-of-function mutations have a near-complete penetrance in ASD. Neurons generated from people with ASD and SHANK2 mutations develop larger dendritic trees and more synaptic connections than those from healthy controls. In addition, common mutations in SHANK2 have been linked to bipolar disorder. == References ==