Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene

Abstract

Prolidase is cytosolic manganese dependent exopeptidase responsible for the catabolism of imido di and tripeptides. Prolidase levels have been associated with a number of diseases such as bipolar disorder, erectile dysfunction and varied cancers. Single nucleotide polymorphism present in coding region of proteins (nsSNPs) has the potential to alter the primary structure as well as function of the protein. Hence, it becomes necessary to differentiate the potential harmful nsSNPs from the neutral ones. 19 nsSNPs were predicted as damaging by in-silico analysis of 298 nsSNPs retrieved from dbSNP database. Consurf analysis showed 18 out of 19 substitutions were present in the conserved regions. 4 substitutions (D276N, D287N, E412K, and G448R) that observed to have damaging effect are present in catalytic pocket. Four SNPs listed in splice site region were found to affect splicing of mRNA by altering acceptor site. On 3′UTR scan of 77 SNPs listed in SNP database, 9 SNPs were lead to alter miRNA target sites. These results provide a filtered data to explore the effect of uncharacterized nsSNP and SNP related to UTRs and splice site of prolidase to find their association with the disease susceptibility and to design the target dependent drugs for therapeutics.