Abstract                                                                                                                                                             

Hypoxanthine phosphoribosyltransferase is a key player in the purine salvage pathway; hence its transcribing HPRT1 gene is treated as an important housekeeping gene in the mammalian genome. Non-synonymous (ns) changes in the HPRT1 gene are generally not tolerated and may cause genetic diseases including Lesch-Nyhan Syndrome (LNS) in humans. To find out such genetic disease in bovines due to HPRT1 gene (on X-chromosome) mutation, this study was carried out. In this study, the effects of nsSNPs in the HPRT1 gene of cattle retrieved from the Ensembl-Biomart were assessed in silico. These nsSNPs were analysed for deleterious effects as well as structural changes associated with the mutants. Among 22 nsSNPs, a total of nine were predicted as deleterious by SIFT, PROVEAN and PANTHER online tools. All nine SNPs showed a decrease in stability using I-mutant 2.0 and MuPro. One nsSNP (rs465703426, G140V) with the highest deleteriousness based on scores of these tools was found to be the most damaging to the native structure along with significant deviation in energy minimization. The Protein network analysis revealed the linkage of 10 other proteins associated with important functions like cell growth and nucleotide biosynthesis. Alteration in HPRT1 may lead to affection to these linked protein functions and might affect the regulation of cellular growth. In this first attempt to assess the deleterious effects of mutations in the bovine HPRT1 gene, the study provides an indication of its harmful implications in the purine salvage pathway.

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