In silico characterization of structural and functional impact of the deleterious SNPs on FSHR gene

Abstract

FSHR is an important gene which plays a major role in the development of secondary sex characteristics and influences the female reproductive cycle by regulating the Follicle Stimulating Hormone. Though this gene and its protein are extensively studied, no attempts have been made yet to methodically analyze the variants in this gene. One of the chief objectives during the analysis of human genetic variation is to distinguish between the Single Nucleotide Polymorphisms (SNPs) that are functionally neutral from those that contribute to the disorder. To predict the possible impact of SNPs on the FSHR structure and function, data were obtained from NCBI (dbSNP and dbVar) and validated manually. Various bioinformatics tools were used to predict the alterations at transcriptional, post transcriptional stages and protein interaction. Around 38 variants reported by NCBI Variation Viewer were sorted by SIFT and 14 of them were reported damaging, 13 were reported to be either benign or damaging by PROVEAN and Panther. From these 13 SNPs, the most damaging (11 SNPs) were modeled using Pymol and the energy difference between the native and mutated structure was calculated by Swiss PDB – Viewer. Based on our analysis, we have reported potential candidate SNPs for the FSHR gene involved in the regulation of ovarian pathophysiology.