Identification of deleterious mutation in CHEK2 gene an insilico approach

Author Name(s): Punyadeep,Priyanka singh,C. Sudandiradoss*
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Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. The current study reports, of the total of 682 SNPs in the CHK2 gene, 10 non-synonymous SNPs (nsSNPs) were identified as functionally significant. SIFT, PolyPhen and I -Mutant programs were used to analyze the nsSNPs. Out of total 10 nsSNPs, 8 were found to be deleterious by SIFT and 5 were damaging as per the PolyPhen program. The complete analysis of these mutations has been the focus of the paper. The structural stability of the mutated structures was studied using I- Mutant program. From a comparison of the stabilizing residues of the native and mutant proteins, we propose that the nsSNP rs121908706, rs121908705, rs121908701, rs112032633and rs111292981) could be important candidates for the various cancers caused by the mutation in CHEK2 gene.


CHEK2 gene, SIFT, PolyPhen, I-Mutant.


CHEK2 is the symbol for the human gene CHK2 checkpoint homolog. It is located on the long (q) arm of chromosome 22 at position 11[3]. The CHEK2 gene give signals for making a protein termed checkpoint kinase 2 (CHK2). This protein acts as a tumor suppressor, which regulates cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. Damaged DNA or the breakage in the DNA strands activates the CHK2 protein. In response to DNA damage, the CHK2 protein interacts with several other proteins, including tumor protein 53. These proteins halt cell division and determine whether a cell will repair the damage or undergo for apoptosis.


The human CHEK2 gene was investigated in this work. The work was done by evaluating the influence of functional SNPs through computation methods and the most deleterious non-synonymous SNPs (nsSNPs) among the CHEK2 gene coding for CHK2 protein kinase were predicted. Out of total 682 SNPs in the CHEK2 gene, 10 were found to be non synonymous. From among these 10 nsSNPs, 8 were found to be deleterious by SIFT and 5 were found damaging as per the PolyPhen Program and 5 nsSNPs were found to be common in both the SIFT and the PolyPhen program. PolyPhen showed that rest of the SNPs is in probably damaging or benign conditions while I – Mutant program showed the structural instability after mutations at these sites. It was found that mutations in CHEK2 gene at the positions 517,404,445 (in rs121908706), 282,239 (in rs121908705), 224,181(in rs121908701), 30(in rs112032633) and at 67(in rs111292981) show a potential deleterious effect on the function of this protein which is probably the reason for causing breast cancer, Li-Fraumeni syndrome, and other cancers like prostate, lung, colon, kidney, thyroid and ovarian cancer. The results of this study have therefore provided novel evidence of the correlation using human data, in turn facilitating genotyping efforts in future molecular epidemiological studies and providing targets for phenotypic analysis of genetic variants.

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