Abstract
CCND1 encodes for Cyclin D1 protein and single-nucleotide polymorphisms (SNPs) can modulate its activity. In the present study, the impact of CCND1 SNPs on structure and/or function of Cyclin D1 protein using in silico tools was investigated. Our analysis revealed only one splice site SNP (c.1988+5G<A) can effect CCND1 function. Subsequently, 78 out of 169 missense variants were predicted as pathogenic by Polyphen2, SIFT, PROVEAN, SNPs&GO, and PANTHER, and 4/78 missense SNPs were further evaluated because these four SNPs were found to be reside in highly conserved region of Cyclin D1. However, they did not show any major impact on tertiary structure and domain of Cyclin D1 but overall R15S and A190S has displayed a significant diseased phenotype and an altered molecular mechanism predicted by MutPred, FATHMM, SNPeffect, SNAP2, and PredictSNP. Consistently, A190S, R179L, and R15S may also cause a decrease in stability of Cyclin D1 anticipated by I-Mutant, HOPE and SNP effect. Furthermore, the Kaplan–Meier plotter has explained that high expression of CCND1 is associated with less survival rate of breast cancer patients. Altogether our study suggests that c.1988+5G<A, R15S, R179L, and A190S SNPs could directly or indirectly destabilize Cyclin D1.
Highlights
Breast cancer is a heterogeneous type of cell carcinoma with high rate of morbidity and mortality in women [1]
We have collected CCND1 single-nucleotide polymorphism (SNP) data from the National Centre for Biotechnology Information (NCBI) genome workbench and applied in silico analysis on coding nonsynonymous SNPs, splice site SNPs and 5 and 3 UTR SNP to predict their pathogenic impact on protein structure and function in relation with breast cancer
Further analysis indicated that A190S, R179L, and R15S may cause a decrease in stability of Cyclin D1 anticipated by I-Mutant, HOPE, and SNPeffect
Summary
Breast cancer is a heterogeneous type of cell carcinoma with high rate of morbidity and mortality in women [1]. Since 2008, every year approximately 2 million cases of breast cancer are being diagnosed and approximately 50% cases belonged to developing countries with high rate of mortality [2]. Due to dwindling resources, lack of high-throughput and innovative technologies to deal the breast cancer management and diagnosis is the major reason of continuously increasing cases of breast cancer in developing countries. It has been reported that breast cancer cases are going to increase in young women. The evidence has demonstrated that women with age
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