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An In Silico Evaluation of Deleterious Nonsynonymous Single Nucleotide Polymorphisms in the ErbB3 Oncogene

机译:ErbB3致癌基因中有害非同义单核苷酸多态性的计算机评估。

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ErbB3 is a significant oncogenic target that is involved in the development of numerous malignancies. In the present in silico study, we evaluated the structural and functional impact of single nucleotide polymorphisms (SNPs) on the ErbB3 gene. The nonsynonymous SNPs (nsSNPs) are known to be deleterious or disease-causing variations because they alter protein sequence, structure, and function. Out of a total 531 SNPs in ErbB3 , we investigated 77 coding nsSNPs and observed that 20 of them could be expected to alter the protein's function based on the predictions of both sequence homology–based (SIFT) and structural homology–based (Polyphen) algorithms. Thereafter, we computed the stability of mutants in units of free energy using I-Mutant 3.0, MuStab, and iPTree-STAB programs and identified seven crucial point mutations (V89M, V105G, C290Y, I418N, R669C, I744T, and A1131T) in epidermal growth factor receptor 3 that are manifested as nsSNPs. Furthermore, FASTSNP determined 14 synonymous SNPs that may have a profound impact on splicing regulation. The computational study identified seven novel hotspots predicted to maintain the native structural conformation and functional activity of ErbB3 and may account for cancer if mutated.
机译:ErbB3是重要的致癌靶标,涉及许多恶性肿瘤的发展。在目前的计算机研究中,我们评估了单核苷酸多态性(SNP)对ErbB3基因的结构和功能影响。已知非同义SNP(nsSNP)是有害或致病变异,因为它们会改变蛋白质序列,结构和功能。在ErbB3的531个SNP中,我们调查了77个编码nsSNP,并根据基于序列同源性(SIFT)和基于结构同源性(Polyphen)算法的预测,预期其中20个会改变蛋白质的功能。此后,我们使用表皮中的I-Mutant 3.0,MuStab和iPTree-STAB程序计算了以自由能为单位的突变体的稳定性,并确定了表皮中的七个关键点突变(V89M,V105G,C290Y,I418N,R669C,I744T和A1131T)表现为nsSNP的生长因子受体3。此外,FASTSNP确定了14个同义SNP,它们可能对剪接调控产生深远影响。计算研究确定了七个新的热点,预计它们将保持ErbB3的天然结构构象和功能活性,并且如果发生突变则可解释癌症。

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