Among these are the brain expressed UBE3 enzymes: the founder of the subclass Ubiquitin Ligase E3A (UBE3A), with its gene loss-of-function resulting in Angelman syndrome (AS) and Ubiquitin Ligase E3B (UBE3B), linked to Kaufman oculocerebrofacial syndrome (KOS) as well as ASD-associated Ubiquitin Ligase E3C (UBE3C). This evidence concerns the gene UBE3B and Angelman syndrome.