In silico approach for the prediction of functional nsSNPs in WIF1 gene of WNT pathway

S. Sunkar, M. Aravind, S. Reddy, D. Neeharika
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Abstract

WNT pathway is generally involved in controlling gene expression and cell behaviour. Earlier studies revealed that mutations in genes of WNT pathway lead to different types of cancer. In our study, cancer related novel gene candidate, WNT inhibitory factor 1 (WIF1) involved in WNT pathway was analysed for potentially deleterious non-synonymous single nucleotide polymorphisms (SNPs). From the dbSNP, the SNPs were retrieved and analysed using various computational tools for their pathogenicity and stability. A total of 36 mutations were identified to be deleterious and decrease the stability. The WIF domain region was considered where the mutations A73E, A73V, R71G were found to be potentially deleterious. These proteins with and without mutations were modelled and compared. Further, it was identified that three deleterious mutations were in the WIF1 protein binding site 1 suggesting their possible role in disease mechanism and can be considered as a potential drug target for various cancers in humans.
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WNT通路中WIF1基因功能性非单核苷酸多态性的计算机预测方法
WNT通路通常参与控制基因表达和细胞行为。早期研究表明,WNT通路基因突变可导致不同类型的癌症。在我们的研究中,我们分析了与癌症相关的新候选基因WNT抑制因子1 (WIF1)参与WNT通路的潜在有害的非同义单核苷酸多态性(SNPs)。从dbSNP中提取snp,并使用各种计算工具分析其致病性和稳定性。共有36个突变被鉴定为有害的,并降低了稳定性。WIF结构域被认为是突变A73E、A73V、R71G具有潜在危害性的区域。对这些有突变和没有突变的蛋白质进行建模和比较。此外,在WIF1蛋白结合位点1中发现了三个有害突变,这表明它们可能在疾病机制中起作用,并且可以被认为是人类各种癌症的潜在药物靶点。
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