Insilco Analysis of Non-Synonymous Single Nucleotide Polymorphisms of GATA 2 binding factor Human Gene

Abstract

GATA2 or GATA-binding factor 2 is a transcription factor, which regulates the expression of genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming lymphatic system-forming, and other tissue-forming stem cells. GATA2 protein is encoded by the GATA2 gene which often suffers germ line and somatic mutations which lead to a wide range of familial and sporadic diseases. Association of data including protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity were predicted using Gene MANIA software. This gene was investigated in NCBI database and the Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) were analyzed by computational software, (SIFT, PROVEAN, Polyphen-2, SNPs&GO, PHD-SNPs, I-Mutant and MUpro). The Protein structural analysis was done by modelling of amino acid substitutions using Project Hope for all predicted pathological polymorphisms. GeneMANIA results showed that GATA 2 gene was associated with 20 other genes. It interacts mainly with ZFPM1 gene (Zinc Finger Protein), FOG family member 1and HDAC5 histone deacetylase5. A total of 246 nsSNPs were obtained from the SNPs database in NCBI consisting of 47 Deleterious predicted by SIFT software. Using PROVEAN 41 SNPs were predicted to have deleterious effect, 17 SNPs were predicted to be damaging by (Polyphen- 2), while 4 SNPs were benign, 14 SNPs were found to be disease related using SNPs&GO and 30 SNPS were found to be disease related using PHD- SNP. By using I-MUTANT and MUPRO software the stability of the protein was predicted. From the results of SIFT, PROVEAN and PolyPhen-2 with respect to PHD-SNPs and SNPs&GO software programs, 6 nsSNPs (rs148942346 (R344I), rs371096438 (P385N), rs387906629 (R398W), rs387906629 (R384W), rs387906633 (C359R) and rs387906633 (C373R)) were predicted to be deleterious, damaging, affecting the protein stability and related to the formation of a disease variants. These results might be beneficial for a precise diagnosis of GATA2 deficiency and related myeloid neoplasm.