Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) in the Human Interleukin 12B Gene: Identification and Structural Characterization

Awad A. Algarni


Background: Interleukin -12B (IL12B) polymorphism has been identified as a factor in the development of various Immunological disorders and cancer. The objective of this study was to identify the non-synonymous SNPs (nsSNPs) with the strongest predicted negative impact on the function of the IL12B protein.

Methods: We employed a variety of computational methods, including SIFT, PolyPhen2, PROVEAN, SNAP2 to determine the functional impact of nsSNPs. Also, In order to investigate the potential association of nsSNPs in the IL12B gene with disease, a computational analysis was conducted using PhD-SNP, SNP&GO, and Pmut. Additionally, I-mutant and MuPro were employed to predict protein stability, while ConSurf was used to identify functional domains and conserved amino acid residues within the protein. Furthermore, SOPMA was used in combination with Project Hope and MutPred2 to predict the impact of mutations on both the structure and function of proteins. Finally, we used GeneMania to analyze the gene-gene interactions of the IL12B gene with other genes.

Results: Our results indicate that nine nsSNPs (G72C, G86C, C90R, C131S, Y136D, P235L, V254G, Y258H and P259S) were found to be potentially deleterious in the IL12B gene.

Conclusion: Our study emphasizes the significance of identifying functional and structural polymorphisms in the IL12B gene, as they may reveal potential therapeutic targets and provide insight into the underlying mechanisms of related diseases. Further experimental investigation is necessary to fully explore the role of these nsSNPs in disease pathogenesis.

Keywords: Interleukin 12B; deleterious nsSNPs; Polymorphisms.; Computational analysis;

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