In Silico analysis of missense substitutions in RB1 gene and their effect on metabolic pathways

Retinoblastoma (rb) is a neonatal intraocular tumor caused by biallelic inactivation of rb1 gene encoding 928 amino acids long nuclear phosphoprotein (prb),which contains three important regions: n-terminal domain,central ab-box and c-terminal domain. homology modeling was performed for three dimensional structure prediction of prb,to predict the potential consequences of three missense mutations (p.thr307ile,p.leu688pro,p.asp316ile) identified by direct sequencing in pakistani rb patients. keeping in view the importance of molecular diagnosis,we performed in silico protein analysis using prosa and project hope to predict the possible structural changes in the mutant rb protein. our analysis concludes that although these mutations do not drastically affect the binding affinity of the protein with its potential legends but seem to be disrupting the normal rb1/e2f pathway leading to deregulation of cell growth control.