SH3 and multiple ankyrin repeat domains protein 2

SHANK2 encodes a 1,849-amino acid adapter protein localized to the postsynaptic density of excitatory synapses (UniProt: Q9UPX8). It functions as a molecular scaffold that interconnects postsynaptic membrane receptors, including NMDA-type and metabotropic glutamate receptors, with the actin-based cytoskeleton, thereby contributing to dendritic spine structure and synaptic organization.

SHANK2 is expressed in neuronal tissues where it plays a critical role in excitatory synapse assembly and function. The protein has been associated with autism spectrum disorder; loss-of-function mutations in SHANK2 are linked to Autism 17 (AUTS17), a neurodevelopmental condition characterized by social communication impairments, restricted interests, and often moderate intellectual disability.

SHANK2 is classified as SFARI Category 1 (SFARI Cat 1), indicating strong evidence for autism susceptibility. Its role as a postsynaptic scaffold protein linking glutamatergic signaling to cytoskeletal dynamics positions it as a key regulator of synaptic plasticity, suggesting that SHANK2 disruption may underlie excitatory-inhibitory imbalance implicated in autism pathogenesis.