Abstract
Background and Aims:
To evaluate the functional and structural impact of deleterious missense single-nucleotide polymorphisms (nsSNPs) on human Interleukin-2 (IL-2), a key cytokine in antifungal immunity.

Methods:
In silico analysis of nsSNPs using bioinformatics tools (MAPP, PhD-SNP, PolyPhen-1/2, SIFT, SNAP, PredictSNP, I-Mutant 2.0, ConSurf, Project HOPE) to predict their effects on protein function and structure. MusiteDEEP was used for post-translational modification analysis.

Results:
Novel deleterious missense nsSNPs were identified in IL-2 (M1T, F62C, 73P, S107I, G118E, and W141R). Computational analyses predicted significant alterations in IL-2’s surface properties, such as altered (signal peptide, transmembrane protein, disordered interface, metal binding, coiled coil, stability, disordered interface), or loss of (N-terminal acetylation, acetylation, strand, loop, transmembrane protein), or gain of (intrinsic disorder, of helix, allosteric site or of relative solvent accessibility), change is hydrophobicity and size were observed. Thus, potentially disrupt interactions with other immune molecules and function. Dramatic changes were obsevered in post-translational modifications for mutations T71I and S107I, resulted in the loss of phosphorylation sites, while the mutations M1T and L92S led to a gain of phosphorylation.

Conclusion:
These findings represents a foundational step in identifying potentially pathogenic IL-2 mutations, suggest the nsSNPs in IL-2 may contribute to impaired antifungal immunity by altering protein function and structure. Further research is warranted to explore the clinical implications of these findings for personalized medicine approaches to fungal infections.

Key words: nsSNPs, IL-2, antifungal, immunity, in-silico, protein, mutations, missense, bioinformatics, polymorphism