Inborn errors E778K and G908R in NOD2 gene increase risk of nontuberculous mycobacterial infection: a computational study

Abstract Background The innate immune system has a critical role in the early detection of pathogens, mainly by relying on pattern-recognition receptor (PRR) signaling molecules. Nucleotide-binding oligomerization domain 2 (NOD2) is a cytoplasmic sensor for recognition of invading molecules and danger signals inside the cells. NOD2’s functions are critical; polymorphisms of its encoding gene are associated with several immune pathological conditions. We recently reported that missense E778K and G908R variants of NOD2 gene are associated with recurrent pulmonary nontuberculous mycobacterial infections Methods This is an in-silico analysis of NOD2 gene using SNPs functionality analyses, post-translational modification site prediction and network analysis. Results Our analysis revealed that these damaging mutations affect the structural properties and function and ligand binding in the mutant receptor. Conclusion The consequence of these mutations may also impress downstream processing and receptor crosstalk with other immune molecules and therefore increase susceptibility to infectious disease.