SHANK1 is located on the 19q13.33 region of chromosome 19 and is composed of 24 exons.
SHANK1 mutations leading to ASD can arise either de novo or be inherited from the parents and include: CNVs (mostly deletion), missense variant and splice mutations.
Penetrance of SHANK1 deletion for ASD seems to be higher in male than females.
Female carriers of SHANK1 deletion often exhibit anxiety disorders without ASD, a comorbidity of ASD.
SHANK1 codes for a scaffolding protein expressed at the synapses of excitatory neurons in different brain areas: cortex, thalamus, hippocampus, cerebellum, hypothalamus and substantia nigra.
SHANK1 protein comprises 5 protein domains allowing the interaction of a wide number of synaptic proteins like receptors as well as actin cytoskeleton and signaling proteins. Abnormalities in SHANK1 functions may alter synaptic communications between neurons in regions underlying cognitive functions.