Structure-function studies to characterize UBE3A missense variants
A potentially valuable approach to understand UBE3A function is the characterization of non-truncating missense variants that change one or a few amino acids in the protein. There are hundreds of UBE3A variants, and their functional significance is virtually unknown.
The goals of this study are:
- Create the first complete functional catalogue of UBE3A missense variants and use insights from these studies to uncover new information about UBE3A enzyme function. This will provide supportive evidence to aid the diagnosis of AS.
- Identify mutations in UBE3A that have an unusually large influence on enzyme activity. The investigators hope to find structural hotspots within UBE3A that are critical for enzyme function and provide an explanation of the molecular function of UBE3A in the nervous system.