CYP2R1 and CYP27A1 genes: An in silico approach to identify the deleterious mutations, impact on structure and their differential expression in disease conditions

• Published in: Genomics (San Diego, Calif.) Calif.), 2020-09, Vol.112 (5), p.3677-3686
• Main Authors: Sunkar, Swetha, Neeharika, Desam
• Format: Article
• Language: English
• Subjects: CYP27A1; CYP2R1; Differential expression; Interactions; Modeling; nsSNPs
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2020.04.017

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. •nsSNPs were retrieved from dbSNP for CYP2R1 and CYP27A1 genes that are associated with impaired 25-hydroxylase activity indirectly disturbing the vitamin D metabolism.•Pathogenicity, stability and conservancy analysis of the mutations were analyzed using different algorithms based computational tools based on which 11 and 35 mutations from CYP2R1 and CYP27A1 genes respectively were identified as deleterious.•Structural level analysis of the native proteins namely Q6VVX0 (CYP2R1) and Q02318 (CYP27A1) and their mutant models was performed.•Interaction of native and mutant protein with cholecalciferol was carried out to find the effect of these variations on the function of the proteins.•Variation in the expression levels of these genes was observed in lung cancer, skin cancer, rheumatoid arthritis and osteoarthritis datasets.