CCND1 encodes for Cyclin D1 protein and single nucleotide polymorphisms (SNPs) can modulate its activity. In the current 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, SNP & 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 SNPeffect. 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.

中文翻译：

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细胞周期蛋白 D1 基因 SNP 的计算分析与乳腺癌的关联。

CCND1 编码细胞周期蛋白 D1 蛋白，单核苷酸多态性 (SNP) 可以调节其活性。在当前的研究中，使用计算机工具研究了 CCND1 SNP 对细胞周期蛋白 D1 蛋白的结构和/或功能的影响。我们的分析显示只有一个剪接位点 SNP (c.1988+5G<A) 可以影响 CCND1 功能。随后，Polyphen2、SIFT、PROVEAN、SNP & GO 和 PANTHER 预测 169 个错义变异中的 78 个具有致病性，并且进一步评估了 4/78 个错义 SNP，因为发现这四个 SNP 位于细胞周期蛋白 D1 的高度保守区域. 然而，它们对细胞周期蛋白 D1 的三级结构和结构域没有任何重大影响，但总体 R15S 和 A190S 显示出显着的患病表型和 MutPred、FATHMM、SNPeffect、SNAP2、和预测SNP。一致地，A190S、R179L 和 R15S 也可能导致 I-Mutant、HOPE 和 SNP 效应预期的细胞周期蛋白 D1 稳定性的降低。此外，Kaplan-Meier 绘图仪解释了 CCND1 的高表达与乳腺癌患者的较低存活率有关。总之，我们的研究表明，c.1988+5G<A、R15S、R179L 和 A190S SNP 可以直接或间接破坏细胞周期蛋白 D1 的稳定性。