Mutations in <i>SHANK1-3</i> are prevalent in patients with autism spectrum disorders (ASD), and loss of one copy of <i>SHANK3</i> causes Phelan-McDermid Syndrome, a syndrome in which Autism occurs in >80% of cases.
Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability.
The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism.