Bioinformatic analysis of some RAG mutations contributing to the primary immunodeficiencies. | ||
| Minia Journal of Medical Research | ||
| Articles in Press, Accepted Manuscript, Available Online from 04 June 2023 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/mjmr.2023.210031.1391 | ||
| Authors | ||
| Mariam M. Fawzy* ; Maiiada H. Nazmy; Moustafa Fathy | ||
| Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt | ||
| Abstract | ||
| Recombination activating genes (RAG) encode RAG1/2 proteins which catalyze formation of DNA double strand breaks (DSB) between variability (V), diversity (D) and joining (J) segments of genes encoding immunoglobulins (Ig) and T-cell receptors (TCR) and rejoining of these segments to allow the unlimited production of (Ig)s and (TCR)s and to maintain durable adaptive immunity. RAG1 structure is composed of enzymatically active core and regulatory non-core. Large numbers of RAG1 mutations were reported in primary immunodeficiencies. In this study, we aimed to analyze some of these mutations and compare the results with the clinical significance displayed on the online websites like NCBI and HGMD. For this purpose, a protein remodeling program called Pymol and other online computational tools like Fathmm, Polyphen-2, SVM-1, Provean, SIFT and CADD were used to recognize the special effect of each mutation on the protein 3D structure. Our findings showed that R507W, W522C, R737H, R778Q, R841W, A857V, F974L, R975W RAG1 mutations have damaging effect as displayed by the computational analysis and this result agreed with what mentioned in the websites. Additionally, H612R and R1006V were found to be more tolerable than others which also concurred with the websites. However, M435V RAG1 mutation has been described as pathogenic in NCBI while most computational programs defined it as benign. In conclusion, Pymol and the computational tools are in co-ordination with the clinical significance described by the mentioned websites except in case of M435V mutation. | ||
| Keywords | ||
| RAG1; Mutation; Pymol; Computational tools | ||
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