In Silico Analysis of Pathogenic Missense Mutation in GBA protein for Gaucher Disease

Gaucher disease (GD) is a common hereditary lysosomal storage disorder which is mainly caused by mutations in the glucocerebrosidase (GBA) gene, leading towards glucosylceramide accumulation in lysosomal macrophages. Understanding the pathogenicity of GBA mutations is crucial for the diagnosis and treatment plan for patients. For this purpose, we conducted in-silico analyses of previously identified 13 missense mutations on GBA gene from an Iranian population. Multiple in-silico tools were employed for the prediction of pathogenicity and stability of the mutations. Out of this pool of mutations, three mutations (p.L393V, p.S439G, p.L483P) were prioritized based on pathogenicity score. Moreover, conservation analysis across multiples species revealed higher conservation at mutation sites, especially for the site of p.S439G. In-silico physicochemical analysis also highlighted significant changes in properties for p.S439G. Our findings demonstrate the effectiveness of in-silico tools in prioritizing pathogenic mutations of GB and provide insights into the molecular consequences of GBA mutations in GD.