Autosomal recessive missense and nonsense variants in KICS2were identified in 11 affected individuals with intellectual disability. Functional characterization in cell culture models and zebrafish showed a loss-of-function mechanism leading to a dysregulation of mTORC1 activity upon nutrient deprivation. Interaction with other KICSTOR complex members was shown to be disrupted for some variants. So far, two missense variants have been identified, while the remaining variants are nonsense variants.
Diagnostic testing for KICS2 activity is not yet established but variants can be tested in cell culture models via mTORC1 activation
KICS2