GBAviewer: a structural database of GBA1 variants in Parkinson's disease

GBAviewer is an interactive database that maps genetic variations in the GBA1 gene, which is associated with Parkinson's disease (PD), onto the structure of the GCase enzyme. This innovative platform serves as a centralized resource for researchers to understand the structural consequences of most GBA1 variants, which have previously remained uncharacterized.

Developed by researchers, GBAviewer integrates multiple data sources, including crystal structures, cryo-electron microscopy complexes, AlphaFold3 models, and AlphaMissense scores. These diverse data sets enable users to visualize the impact of specific GBA1 variants on the GCase enzyme, as well as its interactions with other proteins, such as LIMP-2 and SapC, and potential therapeutic compounds.

One of the key findings of GBAviewer is the mapping of variants in three-dimensional space across various regions of the GCase enzyme, including the active site, LIMP-2 and SapC surfaces, chaperone pockets, and the dimerization interface. Moreover, the platform's AlphaFold3-based model supports previous research by demonstrating that SapC binds to the GCase active site entrance, where several GBA1 variants of unknown significance tend to cluster.

As a freely accessible platform, GBAviewer offers a valuable tool for structural analysis of GBA1 variants, facilitating mechanistic studies and the development of novel therapeutic strategies for Parkinson's disease. This resource can be accessed at https://g-can.shinyapps.io/GBAviewer/.