Bioinformatics Prediction of Rs104894099 Pathogenicity in Cdkn2a Gene As A Tumor Suppressor Gene (Tsg)

Background and aim: cdkn2a gene, localized on 9p21.3 and encoding two suppressor proteins p16 and p14, is a tumor suppressor gene and cell cycle regulator. cdkn2a alterations have been discovered in different types of cancer like leukemia and melanoma, etc. identified alterations in this gene are included promotor hypermethylation, sequence deletions and point mutations. some of single nucleotide variants cause deleterious effects on protein function. our purpose is determination of pathogenicity of rs104894099 in cancer malignancy.methods: in this study, one snp (rs104894099) has been identified and considered in cdkn2a gene. in the rs104894099, valine amino acid in position 59, located in α-helix structure, change to glycine (t>g) or glutamic acid (t>a). this consideration has been studied using various bioinformatics tools including polyphen-2, i-mutant 2.0, provean and sift database. we simulated both of the mutant and wild type protein structures using vmd software.results: sift database (score for v>e and v>g: 0.000), phd-snp, provean (score for v>e: -5.24, for v>g: -5.98) and polyphen-2 (score for v>e: 0.999, for v>g: 0.998) predict that rs104894099 has deleterious effect. i-mutant 2.0 predicts that this snp decreases protein stability. expasy tools showed us that hydrophobicity is decreased in mutant protein. the angles and length of bonds as well as the distances of atoms in mutant and wild type protein have been measured using vmd software. by comparing the mentioned parameters we found that the protein structure does not change in v59e/v59g mutations. conclusion: after using multiple bioinformatics tools, rs104894099 might have pathogenic effects in the cdkn2a gene.