SHANK3

SH3 and multiple ankyrin repeat domains 3 (Shank3), also known as proline-rich synapse-associated protein 2 (ProSAP2), is a is_associated_with::protein that in humans is encoded by the SHANK3 is_associated_with::gene on is_associated_with::chromosome 22. Additional isoforms have been described for this gene but they have not yet been experimentally verified.

Function
This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect is_associated_with::neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in is_associated_with::synapse formation and is_associated_with::dendritic spine maturation.

Clinical significance
Mutations in this gene are associated with is_associated_with::autism spectrum disorder. This gene is often missing in patients with 22q13.3 deletion syndrome, although not in all cases.

Interactions
SHANK3 has been shown to interact with is_associated_with::ARHGEF7.

Mouse models
Mouse models of Shank3 include N-terminal knock-outs and a PDZ domain knock-out all of which also show social interaction deficits and variable other phenotypes. Most of the these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous.