SHANK3 is located on the 22q13.3 region of chromosome 22. This gene is composed of 23 exons.
SHANK3 mutations lead to ID/ASD are in majority de novo and include: CNVs, short indels, missense and nonsense mutations.
SHANK3 codes for a scaffolding protein expressed at the synapses of excitatory neurons in different brain areas: cortex, thalamus, hippocampus, cerebellum, striatum. At the subcellular level, the SHANK3 protein is also located in the soma and the growth cone of neurons. SHANK3 expression is relatively low during early fetal periods and then increases at 36 weeks post- conception and stays stable along all the life of the individual.
Regulation of the SHANK3 expression involves epigenetic mechanisms such as methylation of CpG island, miRNA and post-translational modifications such as ubiquitination.
SHANK3 protein comprises five protein domains allowing the interaction of a wide number of synaptic proteins like receptors as well as actin cytoskeleton and signaling proteins. Abnormalities in SHANK3 functions may alter synaptic communications between neurons in regions underlying cognitive functions.