In Silico Analysis on Structural and Functional Effect of a Deleterious SNP of CHEK۲ Gene Associated with Prostate Cancer

Background and Aim: Prostate cancer is the second most frequent cancer among men, and it is responsible for ۳.۸% of death. One of the genes identified to be involved in this cancer is CHEK۲.CHEK۲ is located on chromosome ۲۲, and it is the upstream regulator of p۵۳ in the DNA-damage– signaling pathway. For this gene is important in both sporadic and familial prostate cancer, it could be an important gene to be investigated for cancer therapy. Here the rs۲۸۹۰۹۹۸۲ mutation on CHEK۲ gene was investigated to understand weather it has any effect on protein and consequently on prostate cancer or not.Methods: The data that was collected by Entrez Gene on National Center for Biological Information (NCBI) web site on human checkpoint kinase ۲ (CHK۲). The effect of a pathogenic mutation on the protein expressed by CHEK۲ gene has been investigated by using SIFT, PolyPhen, I-Mutant and ExPASy servers. By these servers, the stability, structure, hydrophobicity, and function of protein was searched.Results: the results gained by SIFT, PolyPhen, I-Mutant and ExPASy servers showed that this mutation have a significant effect on protein. It showed that the hydrophobicity changes from -۴.۵۰۰ to -۰.۴۰۰, and the results of SIFT, PolyPhen, and I-Mutant predicted this mutation as harmful.Conclusion: In this article, ۱۱۷th residue of CHEK۲ protein was investigated by PolyPhen, SIFT, I-Mutant, and ExPASY server. The rs۲۸۹۰۹۹۸۲ leads to the substitution of nucleotide T with C, and consequently the substitution of Arg with Gly. This mutation by changing hydrophobicity and stability, causes some changes in protein. We hope that these results provide useful information for researchers working on prostate cancer.

کلیدواژه ها:

Prostate cancer ، CHEK۲ ، Mutation ، SNP ، Secondary structure