Department of Otolaryngology, The Third Hospital of Hebei Medical University, Hebei, China.
Department of Otolaryngology, The Second Hospital of Hebei Medical University, Hebei, China.
Sci Rep. 2023 Apr 25;13(1):6774. doi: 10.1038/s41598-023-33764-1.
A single base changes causing a change to the amino acid sequence of the encoded protein, which is defined as non-synonymous single nucleotide polymorphisms (nsSNPs). Many of the nsSNPs can cause disease, and these nsSNPs are considered as pathogenic mutations. In the study, the high-risk nsSNPs of WFS1 and their influence on the structure and function of wolframin protein were predicted by multiple bioinformatics software. We obtained 13 high-risk nsSNPs of WFS1. All the 13 high-risk nsSNPs are highly conserved residues with a conservative score of 9 or 8 and mostly may cause a decrease in protein stability. The high-risk nsSNPs have an important effect on not only amino acid size, charge and hydrophobicity, but also protein's spatial structure. Among these, 11 nsSNPs had been previously published or cited and 2 nsSNPs (G695S and E776K) had not been reported to date. The two novel variants increased or decreased hydrogen bonds. In conclusion, through different computational tools, it is presumed that the mechanism of pathogenic WFS1 nsSNPs should include the changes of physicochemical properties, significant structural changes and abnormal binding with functional partners. We accomplished the computational-based screening and analysis for deleterious nsSNPs in WFS1, which had important reference value and could contribute to further studies of the mechanism of WFS1 related disease. The computational analysis has many advantages, but the results should be identified by further experimental studies in vivo and in vitro.
一个碱基的改变导致编码蛋白质的氨基酸序列发生变化，这种变化被定义为非同义单核苷酸多态性（nsSNP）。许多 nsSNP 可导致疾病，这些 nsSNP 被认为是致病性突变。在研究中，通过多种生物信息学软件预测了 WFS1 的高风险 nsSNP 及其对 wolframin 蛋白结构和功能的影响。我们获得了 WFS1 的 13 个高风险 nsSNP。这 13 个高风险 nsSNP 都是高度保守的残基，保守评分均为 9 或 8，且大多可能导致蛋白质稳定性降低。高风险 nsSNP 不仅对氨基酸大小、电荷和疏水性有重要影响，而且对蛋白质的空间结构也有重要影响。其中，有 11 个 nsSNP 先前已被发表或引用，有 2 个 nsSNP（G695S 和 E776K）迄今尚未报道。这两种新的变体增加或减少了氢键。总之，通过不同的计算工具，推测致病性 WFS1 nsSNP 的机制应包括理化性质的变化、显著的结构变化和与功能伴侣的异常结合。我们完成了 WFS1 中有害 nsSNP 的基于计算的筛选和分析，这对进一步研究 WFS1 相关疾病的机制具有重要的参考价值。计算分析有许多优点，但结果应通过体内和体外的进一步实验研究来确认。
