Researches have revealed that functional non-synonymous Single Nucleotide Polymorphism (nsSNPs) present in the Zinc-finger with UFM1-Specific Peptidase domain protein (ZUFSP) may be involved in genetic instability and carcinogenesis. For the first time, we employed in-silico approach using predictive tools to identify and validate potential nsSNPs that could be pathogenic. Our result revealed that 8 nsSNPs (rs 112738382, rs 140094037, rs 201652589, rs 201847265, rs 202076827, rs 373634906, rs 375114528, rs 772591104) are pathogenic after being subjected to rigorous filtering process. The structural impact of the nsSNPs on ZUFSP structure indicated that the nsSNPs affect the stability of the protein by lowering ZUFSP protein stability. Furthermore, conservation analysis showed that rs 201652589, rs 140094037, rs 201847265, and rs 772591104 were highly conserved. Interestingly, the protein-protein affinity between ZUFSP and Ubiquitin was altered rs 201652589, rs 140094037, rs 201847265, and rs 772591104 had a binding affinity of - 0.46, - 0.83, - 1.62, and - 1.12 kcal/mol respectively. Our study has been able to identify potential nsSNPs that could be used as genetic biomarkers for some diseases arising as a result of aberration in the ZUFSP structure, however, being a predictive study, the identified nsSNPs need to be experimentally investigated.
Keywords: Binding affinity; Cancer; Genetic biomarkers; Single nucleotide polymorphism; ZUFSP.