In silico analysis of missense SNPs in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders

Abstract

Abstract Background Neurodevelopmental disorders are disorders that are generally seen in the early developmental period of an individual's life and involve more than one disease that causes disruptions in the central nervous system. These disorders can be given as examples of diseases such as autism, mental retardation, some epileptic disorders, communication disorders, and mental retardation. The aim of this study is to determine the possible harmful effects of missense single nucleotide polymorphisms (SNPs) in the GABRA1, GABRB1, and GABRB3 genes, which are associated with neurodevelopmental disorders, on the structure and stabilization of the protein, using in silico methods. Software tools SIFT, PolyPhen-2 HumVar, PolyPhen-2 HumDiv, PROVEAN, SNAP2, PHD-SNP, SNP&GO, PANTHER, and Meta-SNP were used to predict harmful SNPs. I-Mutant and MUpro software tools were used to predict the effects of predicted harmful SNPs on protein stabilization. The STRING software tool was used for protein–protein interactions, the GeneMANIA software tool for gene–gene interactions, and the Project HOPE software tool for three-dimensional modeling examples. Results As a result of the bioinformatics analysis, rs121434579, rs139163545, and rs267600530 in the GABRA1 gene; rs74608570, rs75612351, rs78815529 in the GABRB1 gene, and rs7819600779, rs1719850690, rs7819600779, rs171985060690, rs7819600779, rs1719850600779, rs149963014 in the GABRB3 gene were predicted as harmful SNPs. Conclusions In this study, protein structure, function, and stabilization of SNPs known to cause amino acid substitutions in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders were investigated using bioinformatics tools. As a result of the results obtained in our study, it is thought that it will benefit experimental studies and bioinformatics studies.