All missense variants were clustered at the KDM6B catalytic domain (JmjC) and C-terminal helix/zinc motifs, which are important for enzyme-cofactor binding and protein stability.39 Protein structural analysis predicted that most of the damaging missense variants to have a destabilizing effect on the KDM6B protein (Supplementary Data 13), especially those in DDs, while diverging effects were observed for epilepsy and SCZ (Fig. 7b). This evidence concerns the gene KDM6B and epilepsy.