Retinoblastoma 1 (RB1) is the first discovered tumor suppressor gene and recognized as the simple model system whose encoded defective
protein can cause a pediatric
cancer retinoblastoma. It functions as a negative regulator of the cell cycle through the interactions with members of the
E2F transcription factors family. The
protein of the RB1 gene (pRB) is engaged in various cell cycle processes including apoptosis, cell cycle arrest and chromatin remodeling. Recent studies on
Retinoblastoma also exhibited multiple sets of point mutation in the associated
protein due to its large polymorphic information in the local database. In this study, we identified the list of disease associated non-synonymous single nucleotide polymorphisms (nsSNPs) in RB1 by incorporating different computational algorithms, web servers, modeling of the mutants and finally superimposing it. Out of 826 nsSNPs, W516G and W563G were predicted to be highly deleterious variants in the conserved regions and found to have an impact on
protein structure and
protein-
protein interaction. Moreover, our study concludes the effect of W516G variant was more detrimental in destabilizing
protein's nature as compared to W563G variant. We also found defective binding of pRB having W516G mutation with
E2F2 protein. Findings of this study will aid in shortening of the expensive experimental cost of identifying disease associated SNPs in
retinoblastoma for which specialized personalized treatment or
therapy can be formulated.Communicated by Ramaswamy H. Sarma.