Examples include NEDD4-2, which is implicated in periventricular nodular heterotopia37, HECW2, which is implicated in a neurodevelopmental disorder with hypotonia, seizures, and absent language55,56, and HUWE1, which contains a mutation (Y4106C) at a position that is analogous to Q588 in UBE3A and is associated with an X-linked form of intellectual disability57 (Supplementary Fig. 4c). Here, HUWE1 is linked to neurodevelopmental disorder.