Identification of Deleterious Nssnps of Interleukin-2 (IL-2) Gene and Its Structural Stability Using Computational Methods

Fatima Darakhshan, Tayyaba Sadaf


Non-synonymous SNPs (nsSNP) found in the coding regions of a gene cause variations in amino acid residues and are known to influence the function as well as structure of the encoded proteins. Interleukin 2 (IL-2) is described as a proinflammatory cytokine which plays a significant part to govern the response of immune system. It viably contributes in the pathogenesis of several types of cancers and autoimmune diseases. Taking into account the significance of IL-2, a functional examination by various in silico approaches was performed to investigate the probable effect on phenotypic variation due to genetic mutations. In the current study, out of 1071 SNPs, 42 nsSNPs were collected and scrutinized to categorize the deleterious variants. The functional impact of diverse set of mutations was first annotated and protein instability changes were evaluated. Additionally, the protein movement analysis and flexibility of protein at residual level was identified. Secondly, in order to gain insight in protein structural analysis, the IL-2 protein structure was generated; refined modelled structure was then minimized and further assessed by different tools. The conserved regions, solvent accessibility of native protein and structural divergence of mutant models were also estimated. As a result, our study helped to screen the most pathogenic and highly deleterious mutations and suggested that these substitutions may alter the structure–function relationship. It was inferred that the selected nsSNPs can be a vital candidate for diseases caused by the IL-2 gene and other pathological conditions.

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