Bioinformatics Prediction of rs۱۰۴۸۹۴۰۹۹ Pathogenicity in CDKN۲A Gene as a Tumor Suppressor Gene (TSG)

Background and Aim: CDKN۲A gene, localized on ۹p۲۱.۳ and encoding two suppressor proteins p۱۶ and p۱۴, is a tumor suppressor gene and cell cycle regulator. CDKN۲A 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 rs۱۰۴۸۹۴۰۹۹ in cancer malignancy.Methods: In this study, one SNP (rs۱۰۴۸۹۴۰۹۹) has been identified and considered in CDKN۲A gene. In the rs۱۰۴۸۹۴۰۹۹, Valine amino acid in position ۵۹, 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-۲, I-Mutant ۲.۰, 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: ۰.۰۰۰), PHD-SNP, PROVEAN (score for V>E: - ۵.۲۴, for V>G: -۵.۹۸) and PolyPhen-۲ (score for V>E: ۰.۹۹۹, for V>G: ۰.۹۹۸) predict that rs۱۰۴۸۹۴۰۹۹ has deleterious effect. I-Mutant ۲.۰ 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 V۵۹E/V۵۹G mutations.Conclusion: After using multiple bioinformatics tools, rs۱۰۴۸۹۴۰۹۹ might have pathogenic effects in the CDKN۲A gene.

Keywords:

CDKN۲A , Gene , SNP , Bioinformatics tools.