Computational Analysis of Deleterious Single Nucleotide Polymorphisms (SNPs) in Human CALR Gene
Sahar G. Elbager, Hadeel F. Gad Mahgoob, Mohamed Y. Basher, Asia M. Elrashid, Hazem Ghassan Abdo, Shazalia K. Babiker, Ali I. Alsaid, Mohamed Alfaki, Safinaz I. Khalil, Amar A. Dowd, Magdi Bayoumi · American Journal of Bioinformatics Research · 2018
Background: The human Calreticulin (CRT) is a multifunctional protein encoded by CALR gene (CALR) located on chromosome 19. Calreticulin plays an important role in protein folding and calcium homeostasis. It’s also has been associated with cell proliferation, cell cycle progression and immunogenic cell death. High CRT serum levels were reported in various cancer like prostate cancer and breast carcinoma. Being observed as an important molecule in biological responses and its association with various diseases, we aimed to systematically explore the probable effects of CALR genetic variants on functions and structure of calreticulin using in silico prediction softwares. Methods: The data on human CALR gene was retrieved from dbSNP/NCBI. Eleven different prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Condel, Pmut, nsSNPs Analyzer, PhD-SNP, I-Mutant, Mutpred and Project Hope were used to analyzing the effect of nsSNPs on functions and structure of the CRT protein. STRING and KEGG database were used for CRT protein-protein interaction. Results: As per dbSNP database, the human CALR gene investigated in this work contained a total of 682SNPs:53 SNPs in 3′ UTR region, 25 SNPs in 5′ UTR region, 343 SNPs in intron region, 103 SNPs in coding synonymous regions and 154 non-synonymous SNPs (nsSNPs) which comprises of 150 missense mutations, 3 frameshift mutations and one nonsense mutation. We selected missense nsSNPs for our investigation. A total of 4 nsSNPs P216L, R73C, W261G and Y128C were predicted to have the most damaging effects on CRT protein's structure and function. STRING and KEGG revealed that CRT protein had strong interactions with proteins that involved in protein processing and presentation networks. Therefore, any structural alterations in the CRT protein that interfere or harm these networks interactions would probably increase susceptibility to diseases. Conclusion: Based on these analyses, the present study suggested that the reported functional SNPs may act as potential targets in genetic association studies.