Single nucleotide polymorphisms in CCR6 (C–C chemokine receptor type 6) gene have been found to be the possible cause of many diseases like rheumatoid arthritis, psoriasis, lupus nephritis and systemic sclerosis and other autoimmune diseases. Therefore, identification of structurally and functionally important polymorphisms in CCR6 is important in order to study its potential malfunctioning and discovering therapeutic targets. Several bioinformatics tools were used to identify most damaging nsSNPs that might be vital for CCR6 structure and function. The in silico tools included PROVEAN, SIFT, SNP&GO and PolyPhen2 followed by I‐Mutant MutPred and ConSurf. Phyre2 and I‐TASSER were used for protein 3‐D Modelling while gene–gene interaction was predicted by STRING and GeneMANIA. Our study suggested that three nsSNPs rs1376162684, rs751102128 and rs1185426631 are the most damaging in CCR6 gene while 7 missense SNPs rs1438637216, rs139697820, rs768420505, rs1282264186, rs1394647982, rs769360638 and rs1263402382 are found to revert into stop codons. Prediction of post‐transcriptional modifications highlighted the significance of rs1376162684 because it effected potential phosphorylation site. Gene–gene interactions showed relation of CCR6 with other genes depicting its importance in several pathways and co‐expressions. In future, studying diseases related to CCR6 should include investigation of these 10 nsSNPs. Being the first of its type, this study also proposes future perspectives that will help in precision medicines. For such purposes, CCR6 proteins from patients of autoimmune diseases should be explored. Animal models can also be of significance find out the effects of CCR6 in diseases.

中文翻译：

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鉴定人类 CCR6 基因中最具破坏性的 nsSNP：计算机分析

已发现 CCR6（C-C 趋化因子受体 6 型）基因中的单核苷酸多态性是许多疾病的可能原因，如类风湿性关节炎、银屑病、狼疮性肾炎和系统性硬化症等自身免疫性疾病。因此，鉴定 CCR6 中结构和功能上重要的多态性对于研究其潜在的故障和发现治疗靶点很重要。几种生物信息学工具用于识别可能对 CCR6 结构和功能至关重要的最具破坏性的 nsSNP。计算机工具包括 PROVEAN、SIFT、SNP&GO 和 PolyPhen2，其次是 I-Mutant MutPred 和 ConSurf。Phyre2 和 I-TASSER 用于蛋白质 3-D 建模，而基因-基因相互作用由 STRING 和 GeneMANIA 预测。我们的研究表明，三个 nsSNP rs1376162684，rs751102128 和 rs1185426631 是 CCR6 基因中最具破坏性的，而 7 个错义 SNP rs1438637216, rs139697820, rs768420505, rs1282264186, rs196796 和 rs196896 转为 rs196896 到 rs196896 到 rs196896, 43043043043043043634 转录后修饰的预测突出了 rs1376162684 的重要性，因为它影响了潜在的磷酸化位点。基因-基因相互作用显示了 CCR6 与其他基因的关系，描述了它在几个途径和共表达中的重要性。将来，研究与 CCR6 相关的疾病应包括对这 10 个 nsSNP 的调查。作为同类研究中的第一个，这项研究还提出了有助于精准医疗的未来前景。为此，应探索来自自身免疫性疾病患者的 CCR6 蛋白。