Year: 2026
Type: preprint
Abstract: Background GBA1 variants are common risk factors for Parkinson’s disease (PD), yet the structural consequences of most variants remain uncharacterized. No centralized resource currently integrates the growing number of GCase structures, compounds, and PD-associated variants. Objectives To develop an interactive tool mapping GBA1 -PD missense variants onto GCase structures, alongside interactors and therapeutic compounds. Methods We built GBAviewer, an R/Shiny web server integrating GBA1-PD Browser variants with crystal structures, cryo-EM complexes, AlphaFold3 models, and AlphaMissense scores. We also modelled a putative GCase-Saposin C-glucosylceramide ternary complex using AlphaFold3. Results GBAviewer maps variants in 3D across the GCase active site, LIMP-2 and SapC surfaces, chaperone pockets, and dimerization interface. Our ternary model corroborates SapC binding to the GCase active site entrance, where several variants of unknown significance cluster. Conclusions GBAviewer is a freely accessible platform for structural analysis of GBA1 variants, supporting mechanistic studies and therapeutic development. Available at: https://g-can.shinyapps.io/GBAviewer/ .
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7212385056