Predicting the functional consequences of non-synonymous rs121918573 single-nucleotide polymorphism within the plant homeobox finger domain of human recombination activation gene 2
by Dylan Weil; Alexa Fort; Rhiannon Wold Gonzalez; Irina Vlasova-St. Louis
International Journal of Data Mining and Bioinformatics (IJDMB), Vol. 26, No. 3/4, 2021

Abstract: Recombination-activating gene 2 (RAG2) encodes the protein subunit RAG2 of the RAG1/2 endonuclease complex. This complex is well-known for its critical role in generating the diversity of B and T cell receptors. Mutations that impact the function of RAG2 in vitro, in animal models, and in humans result in impaired V(D)J recombination activity, and various forms of severe combined immunodeficiency (SCID). In this study, we evaluated the molecular epidemiology of the SNP rs121918573 (a C>T missense mutation) and examined its potential impact on RAG2 function. Rs121918573 was mapped to the putative zinc-binding site within the plant homeodomain (PHD) region of RAG2. The effect of SNP on RAG2 protein structure was analysed via three-dimensional structure prediction and the impact of a Cys478Tyr mutation on zinc-dependent binding to DNA was visualised. The I-TASSER server was used for the structural prediction of the SNP effect on both DNA and peptide binding. Predictive analyses of the effects of rs121918573 mutation alone showed evidence of destabilisation on the PHD region of the protein but otherwise showed no impact on RAG2 expression. This study provides in-depth bioinformatics analysis of the genomic location of rs121918573 and the effect on the RAG2 gene and protein structure.

Online publication date: Tue, 08-Nov-2022

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