PREDICTIVE MODELING OF N-ACETYL TRANSFERASE 2 SINGLE NUCLEOTIDE POLYMORPHISMS AND BREAST CANCER RISK USING IN-SILCO APPROACHES

Abstract

N-acetyltransferase 2, also known as arylamine N-acetyltransferase, commonly known as NAT2. The objective of this study was to identify non-synonymous SNPs of NAT2 and their association with breast cancer using computational analysis. For this purpose, different online tools like SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2 (to identify pathogenic SNPs), SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER (disease associated SNPs), Mu-Pro, I-Mutant, and CONSURF (to check protein stability) were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, and protein to protein interaction by STRING. Nineteen SNPs having rsIDs (rs1435840670, rs747536177, rs753310036, rs1175197943, rs1805158,rs1019316375, rs201345576, rs1476310549, rs72466458, rs201080763, rs746734312, rs561124342, rs549917500, rs1383708687, rs4986996, rs559660817, rs1344597702, rs749948990, and rs148566670) showing mutations on Y6H, G11V, F37S, H43P, R64W, G65D, W67R, W67C, C68Y, N72S, G83S, G83A, H107Q, V112M, D122N, D122G, C223W, G230V, and L275M, respectively found to be completely deleterious. The PTMs found were Glycosylation at amino acid number 125; Ubiquitination at 256 and 282, Acetylation at 272; Hydroxylation at 281, and Phosphorylation at 287. The protein secondary structure consisted of Alpha helix (Hh) 80 is (27.59%), Extended strand (Ee) 65 is (22.41%), Beta turn (Tt) 21 is 7.24% and Random coil (Cc) 124 is (42.76%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, Liver carboxylesterase 1, Glutathione S-transferase Mu 1, and with cytochrome family. Based on these results, it is concluded that these SNPs found in NAT2 are involved in breast cancer. Further in vitro and in vivo analysis should be performed to conduct these interactions.