Deleterious nonsynonymous SNPs of human VDR and BMP2 genes and their impact on ankylosing spondylitis: a comprehensive in silico analysis

Abstract Background Single-nucleotide polymorphisms (SNPs) influence disease susceptibility, making it essential to identify harmful variants. The vitamin D receptor ( VDR ) and bone morphogenetic protein 2 ( BMP2 ) genes, which regulate bone metabolism, calcium balance, and immune function, are implicated in ankylosing spondylitis (AS). Methods Deleterious non-synonymous SNPs (nsSNPs) in VDR and BMP2 genes, which were identified using various computational tools, such as Polyphen-2, SIFT, Mutation Assessor, Meta-SNP, PhD-SNP, PROVEAN, PANTHER, SNAP-2, and SNPs&GO. Predicted nsSNPs were further analyzed for protein stability (I-Mutant, MUpro, ) evolutionary conservation (ConSurf), protein interaction (GeneMANIA, STRING). and structural impact (Project HOPE) analysis. Results Fourteen missense SNPs in VDR and ten missense SNPs in the BMP2 gene were predicted to be deleterious. Stability analysis indicated that these SNPs altered protein stability, while ConSurf showed that SNPs were located in conserved regions. Project HOPE analysis revealed significant effects on residue physicochemical properties and protein structure. Conclusions The identified deleterious nsSNPs in the VDR and BMP2 genes may contribute to AS susceptibility by affecting protein structure and function. These findings highlight the potential contribution of these nsSNPs in AS susceptibility and could be utilized in future experimental studies. The predicted nsSNPs may also serve as molecular targets for diagnostic and therapeutic applications.