Computational Analysis Revealed Five Novel Mutations in Human IL2RG gene Related to X-SCID

Abstract

ABSTRACTBackgroundX linked severe combined immunodeficiency (X-SCID) is a life-threatening disorder. It is due to mutation of the interleukin two receptor gamma-chain (IL2RG) gene. Nonsynonymous SNPs (nsSNPs) are the most common polymorphism, known to be deleterious or disease-causing variations because they alter protein sequence, structure, and function. Objective: is to reveal the effect of harmful SNPs in the function and structure of IL2RG protein.MethodData on IL2RG was investigated from dbSNP/NCBI database. Prediction of damaging effect was done using sift, polyphen, provean and SNAP2.more software were used for more analysis: phd-snp, and and go, Pmut, Imutant.modeling was done using chimera and project hope. Gene interaction was done by gene mania.3UTR prediction was done using polymiRTS software.ResultThe in-silico prediction identified 1479 SNPs within IL2RG gene out of which 253 were coding SNPs, 50 took place in the miRNA 3 UTR, 21 occurred in 5 UTR region and 921 occurred in intronic regions. a total of 12 missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT) and a structural homology-based method (PolyPhen), Five of them were novel; rs1322436793(G305R), rs1064794027(C182Y), rs111033620(G114D), rs193922347 (Y105C) and rs1293196743(Y91C), Two SNPs(Rs144075871 and rs191726889) out of 50 in the 3UTR region were predicted to disrupt miRNAs binding sites and affect the gene expression.ConclusionsComputational analysis of SNPs has become a very valuable tool in order to discriminate neutral SNPs from damaging SNPs. This study revealed 5 novel nsSNPs in the IL2RG gene by using different software and 21 SNPs in 3UTR. These SNPs could be considered as important candidates in causing diseases related to IL2RG mutation and could be used as diagnostic markers.