Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency (PID), characterized by fatal
opportunistic infections. The ADA gene encodes
adenosine deaminase, an
enzyme that catalyzes the irreversible deamination of
adenosine and
deoxyadenosine in the catabolic pathway of
purine. Mutations of the ADA gene have been identified in patients with
severe combined immunodeficiency. In this study, we performed a bioinformatics analysis of the human ADA gene to identify potentially harmful nonsynonymous SNPs and their effect on
protein structure and stability. Using eleven prediction tools, we identified 15 nsSNPs (H15D, H15P, H17Q, H17Y, D19N, T26I, G140E, C153F, A183D, G216R, H258Y, C262Y, S291L, S291W, and K34OE) as harmful. The results of ConSurf's analysis revealed that all these nsSNPs are localised in the highly conserved positions and affect the structure of the native
proteins. In addition, our computational analysis showed that the H15D, G140E, G216R, and S291L mutations identified as being associated with
severe combined immunodeficiency affect
protein structure. Similarly, the results of the analyses of Rmsd, Rmsf, and Rg showed that all these factors influence protein stability, flexibility, and compaction with different levels of impact. This study is the first comprehensive computational analysis of nsSNPs of the ADA gene. However, functional analyses are needed to elucidate the
biological mechanisms of these polymorphisms in
severe combined immunodeficiency.