The identification of variants in families with X-linked intellectual disability that clustered around the Sec7 and IQ-like domains and resulted in reduced enzymatic activity, provided strong evidence that missense mutations in IQSEC2 cause a neurocognitive disability.18 Affected male patients with these variants displayed non-syndromic ID, with variable penetrance of other comorbidities such as autistic spectrum disorders and seizures. The gene discussed is IQSEC2; the disease is X-linked intellectual disability.