Molecular characteristics

The PPP3CA gene encodes calcineurin A, one component of a protein phosphatase called calcineurin. Calcineurin A has multiple functional domains and different variants may have different molecular consequences. Variants in PPP3CA could cause Loss-of-Function (LoF) or Gain-of-Function (GoF). LoF variants reduce protein expression level or function and cause overt seizures and developmental regression. GoF variants increase calcineurin activities and cause skeletal abnormalities. In addition, variants generating truncating proteins cause more severe early-onset refractory seizures.