RESUMO
Non-synonymous missense SNPs (nsSNPs) in CPE and GNAS genes were investigated computationally. In silico identified nsSNPs were experimentally validated in type II diabetes mellitus (T2DM) in Pakistani Pathan population using next generation sequencing (NGS). Sixty two high-risk nsSNPs in CPE and 44 in GNAS were identified. Only 12 in GNAS were clinically significant. Thirty six high-risk nsSNPs in CPE and 08 clinically significant nsSNPs in GNAS lies in the most conserved regions. I-mutant predicted that nsSNPs decrease the proteins stability and ModPred predicted 20 and 12 post-translational modification sites in CPE and GNAS proteins respectively. Ramachandran plot showed 88.7% residues are in the most favored region of protein models. By experimentation, none of the nsSNPs were found to be associated with T2DM. In conclusion, this study differentiates the deleterious nsSNPs from the neutral ones. Although nsSNPs are not associated with T2DM, they can be targeted in other CPE and GNAS genes related disorders.