UBE3A and Angelman syndrome: Interestingly, nonconservative amino acid substitutions and insertions in the C-tail of E6AP are associated with Angelman's syndrome (missense, G850D; deletion/insertion, A842-T844/RCS; C-terminal insertion QNKIKQKKGRKKKEKI) (80, –, 82) and certain types of cancer (A842D and T844M) (83), likely causing E6AP to malfunction in these settings.