The AS gene, UBE3A, encodes a ubiquitin ligase protein. The diagram below shows the UBE3A gene map location in chromosome region 15q11.2-q13. Blue represents paternally expressed, red represents maternally expressed, and the white circles represent bi-allelically expressed (e.g., on both parental chromosomes) genes. The Imprinting Center is located at a distant site from the UBE3A gene. Repetitive, duplicated elements (duplicons) are displayed as multicolored rectangles and the common breakpoints associated with AS deletions are labeled BP1- BP4. Non-imprinted disorders that map within the AS deletion region include oculocutaneous albinisim type 2 (OCA2) and spastic paraparesis type 6 (SPG6).
The diagram below shows how UBE3A acts in the ubiquitin protein degradation pathway. Important in UBE3A's protein structure is the HECT domain that enables ubiquitination of the target protein (red). Some protein targets for UBE3A are known but it is currently unknown which protein targets are linked to the precise brain dysfunction in AS.
This illustrates the four genetic mechanisms that are known to disrupt UBE3A function. The approximate percentage of each mechanism is indicated, and this number slightly varies depending on which group of AS individuals are studied. The chromosome deletion (number 1) mechanism usually involves chromosome breaking in a region of repetitive elements (labeled as duplicons). The brackets indicate the extent of one of the more common large deletions.
The diagram below recapitulates the information illustrated in the above diagram. Maternal (M) and paternal (P) chromosomes are labeled.
