CNKSR2 was first reported in relation to X-linked complex neurodevelopmental disorder in 2012 (Houge et al. 2012, PMID:22511892). Affected males commonly present with delayed psychomotor development, limited or absent speech, childhood -onset and sleep-related seizures, cognitive deterioration, attention issues, and hyperactivity. Carrier females may be unaffected or mildly affected. To date, at least 17 unique variants predicted to cause loss of function of the protein have been described. In addition to SNVs and indels, whole-gene deletions and intragenic CNVs have also been identified in affected individuals. This gene is intolerant to loss-of function variants (pLI = 1, LOEUF = 0.18, gnomAD v2.1.1). This gene-disease relationship is further supported by expression studies and rescue experiments. In summary, CNKSR2 is definitively associated with X-linked complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Working Group on 12/16/2020 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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