Predicting Pathogenicity Of nsSNPs Associated With Rb1 -- An In Silico Approach

TL;DR

This study uses in silico computational tools to analyze SNPs in the Rb1 gene, identifying mutations likely to impact protein structure and function related to cancer risk.

Contribution

It integrates multiple computational methods to predict damaging SNPs in Rb1, providing insights into genetic variations associated with cancer.

Findings

Identified 17 damaging missense mutations in Rb1.

Predicted strong gene associations with 20 other genes.

Analyzed extensive SNP data from NCBI database.

Abstract

Single nucleotide polymorphisms (SNPs) are variations at specific locations in DNA. Sequence responsible for marking genes associated with diseases or tracking inherited diseases within The family. These variations in the Rb1 gene can cause Retinoblastoma and cancer in the retina Of one eye or both, Osteosarcoma, Melanoma, Leukemias, Lungs, and Breast cancer. First of all,The SNP database hosted by NCBI was used to extract some principal data. The association of Rb1 to Other genes were analyzed by GeneMANIA. Ten different computational tools, i.eSIFT,Polyphen-2, I-Mutant 3.0,PROVEAN, SNAP2, PHD-SNP, PMut, SNPs&GO were used for the screening of damaging SNP for the estimation of conserved regions of amino acids Consurf Server was used for the evaluation of the structural stability of both native and mutant proteins, Project Hope was used to examine the structural effects of mutant protein.GeneMANIA predicted that RB1 Gene was expected to have a strong association with 20 other genes i.e. CCND1 and RBP2 etc. As per data retrieved from dbSNP hosted by NCBI,the Rb1 gene probed in this study carried a total of 36,358 SNPs. 345 were found in 3'UTR, 65 in 5'UTR, and 34,543 were found in the intron region. 844 were coding SNPs, and out of 844, 199 were synonymous And 450 were non-synonymous, including 425 missense, five nonsense, and 20 frameshift mutations. And remaining all are other types of SNPs. We took 425 missense SNPs for our investigation. A total of 17 mutations i.e. D332G, R445Q, E492V, P515T, W516G, V531G, E533K, E539K, M558R,W563G, L657Q, A658T, R661Q, D697H, D697E, P796L and R798W were predicted to have Damaging effects on structure and function of Rb1 protein..