title: Computational analysis of functional single nucleotide polymorphisms associated with the CYP11B2 gene.
abstract: Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3'UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3'UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Minyue
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Boyun
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Urology, the Second Affiliated Hospital (Binjiang Branch) Zhejiang University School of Medicine, Hangzhou Binjiang Hospital, Hangzhou, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
mesh_terms: D019405:Cytochrome P-450 CYP11B2 / Q000737:chemistry / Q000235:genetics; D030561:Databases, Nucleic Acid; D006801:Humans; D056004:Molecular Dynamics Simulation; D020641:Polymorphism, Single Nucleotide; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA
chemical_list: D019405:Cytochrome P-450 CYP11B2
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