Impression of Missense Single Nucleotide Polymorphisms of Leptin Gene on the early onset of Obesity related Infertility in Female

Missense mutations in LEPTIN (LEP) gene are more frequently linked to higher risk of acquiring complex metabolic disorders like obesity, type 2 diabetes and associated female infertility. Some nonsynonymous single nucleotide polymorphisms (nsSNP) in LEP gene affect both the function and structure of LEP protein. Thus, we have used various computational tools like nsSNP analyser, PolyPhen-2, Provean Protein, Fathmm, I-Mutant, SNPs and Go, ConSurf, Net Surf, PhD-SNP, PANTHER and SNP effect to identify the functional single nucleotide polymorphisms (SNPs) and indels in protein structure as listed in the dbSNP database. In our in silico study, we have predicted seven potentially deleterious nsSNPs i.e., rs776443424 (S52F), rs886061972 (D61N), rs200915360 (D76Y), rs748408158 (L86F), rs724159998 (D100Y), rs28954113 (N103K), rs1051206328 (C117S). Using the Swiss PDB viewer, we have also analysed the free energy change and the structural visualization of wildtype and mutant protein. Among the seven nsSNPs, D100Y, D76Y and N103K have direct or indirect thwart on the amino acid interactions and hydrogen bonding networks of LEP. Of these, N103K functionally alters the LEP protein due to high free energy whereas D100Y and D76Y have structural impact. These findings may promote the selection of potential variants for future studies on onset of obesity related infertility in female