Molecular Modelling of nsSNPs in GABRA2 Gene in Epilepsy and Study of Their Impact On Structure and Stability of GABRA2 Protein

Abstract

Epilepsy is a neurological condition characterized by abrupt, unprovoked, and recurrent seizures that are unpredictable in frequency. The objective of this analysis was to identify novel non-synonymous polymorphisms in the GABRA2 gene and determine their effect on protein structure and stability. Most pathogenic/deleterious nsSNPs were predicted using six different bioinformatic tools. Mutpred2, Mupro was used to check the impact of identified nsSNPS on protein structure and stability. The pathogenic score of SNPs was predicted using the FATHMM tool. The CONSURF webserver was used for conservation analysis of pathogenic SNPs.3-D structure of the protein was realized using SWISS-MODEL and residue position in protein visualized by Lite Mol. GeneMANIA and STRING databases were used to predict the function of interlinked gene interactions. Out of 228 nsSNPs retrieved from the dbSNP database, we identified a novel missense variant, F285S (rs41310789), as most deleterious and its possible association with epilepsy syndrome focal epilepsy. Stability and conservation analysis results interpret rs41310789 present in evolutionarily conserved regions of a gene and affect its structure. This analysis provides information regarding the impact of nsSNPs that might affect the structure and activity of GABRA2 protein. Thus, these coding variants should be taken into scrutiny while genetic screening of epileptic patients.