Mutations in CYP2R1 and CYP27A1 involved in the conversion of Cholecalciferol into Calcidiol were associated with the impaired 25-hydroxylase activity therefore affecting the Vitamin D metabolism. Hence, this study attempted to understand the influence of genetic variations at the sequence and structural level via computational approach. The non-synonymous mutations retrieved from dbSNP database were assessed for their pathogenicity, stability as well as conservancy using various computational tools. The above analysis predicted 11/260 and 35/489 non-synonymous mutations to be deleterious in CYP2R1 and CYP27A1 genes respectively. Native and mutant forms of the corresponding proteins were modeled. Further, interacting native and mutant proteins with cholecalciferol showed difference in hydrogen bonds, hydrophobic bonds and their binding affinities suggesting the possible influence of these mutations in their function. Also, expression of these genes in various disease conditions was investigated using GEO datasets which predicted that there is a differential expression in cancer and arthritis.

中文翻译：

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CYP2R1 和 CYP27A1 基因：一种识别有害突变、对结构的影响及其在疾病条件下差异表达的计算机方法。

参与胆钙化醇转化为骨化醇的 CYP2R1 和 CYP27A1 突变与 25-羟化酶活性受损有关，从而影响维生素 D 代谢。因此，本研究试图通过计算方法在序列和结构水平上了解遗传变异的影响。使用各种计算工具评估从 dbSNP 数据库检索到的非同义突变的致病性、稳定性和保护性。上述分析预测 11/260 和 35/489 非同义突变分别在 CYP2R1 和 CYP27A1 基因中是有害的。对相应蛋白质的天然和突变形式进行建模。此外，与胆钙化醇相互作用的天然和突变蛋白显示出氢键的差异，疏水键及其结合亲和力表明这些突变可能对其功能产生影响。此外，使用 GEO 数据集研究了这些基因在各种疾病状况中的表达，该数据集预测在癌症和关节炎中存在差异表达。