Predicting the most deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) of HRAS gene and in silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer

Abstract

Harvey rat sarcoma (HRAS) protooncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was em[loyed in analysing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as “pathogenic” or “harmful”. Stability analysis predicted shortlisted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227 and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS as a hub connecting three clusters consisting of 11 proteins and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses and therapeutic interventions focusing on cancer.