SHANK3 and Cognitive impairment: Interestingly, patients with Shank3 mutations appear to have more-severe cognitive deficits than those with Shank1 or Shank2 mutations, and suggest that Shank3 mutation screening in clinical practice, and perhaps the restoration of the Shank3 gene activity may selectively rescue pathogenic synaptic defects of some ASD-associated behavioral phenotypes (7, 28, 29).