TY - GEN
T1 - In Silico Analysis of Pathogenic Missense Mutation in GBA protein for Gaucher Disease
AU - Eldous, Hend Ghassan
AU - Ali Osman, Maryiam Jama
AU - Basit, Syed Abdullah
AU - Arif, Muhammad
AU - Alam, Tanvir
N1 - Publisher Copyright:
© 2024 Copyright ACM.
PY - 2024/5/17
Y1 - 2024/5/17
N2 - 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.
AB - 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.
KW - GBA protein
KW - Gaucher disease
KW - Missense mutation
UR - http://www.scopus.com/inward/record.url?scp=85204599765&partnerID=8YFLogxK
U2 - 10.1145/3673971.3674003
DO - 10.1145/3673971.3674003
M3 - Conference contribution
AN - SCOPUS:85204599765
T3 - ACM International Conference Proceeding Series
SP - 175
EP - 180
BT - ICMHI 2024 - 2024 8th International Conference on Medical and Health Informatics
PB - Association for Computing Machinery
T2 - 8th International Conference on Medical and Health Informatics, ICMHI 2024
Y2 - 17 May 2024 through 19 May 2024
ER -