The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda.
The African Center of Excellence in Bioinformatics of Bamako (ACE-B), University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
BMC Res Notes. 2021 Dec 20;14(1):457. doi: 10.1186/s13104-021-05879-z.
The Angiotensin 1 converting enzyme (ACE1) gene plays a critical role in regulating blood pressure and thus, it has become a major therapeutic target of antihypertensives. Single nucleotide polymorphisms (SNPs) occurring within a gene most especially at the functional segment of the genes alter the structure-function relationship of that gene.
Our study revealed that five nsSNPs of the ACE1 gene were found to be potentially deleterious and damaging and they include rs2229839, rs14507892, rs12709442, and rs4977 at point mutations P351R, R953Q, I1018T, F1051V, and T1187M. The protein stability predictive tools revealed that all the nsSNPs decreased stability of the protein and the Consurf server which estimates the evolutionary conservation profile of a protein showed that three mutants were in the highly conserved region. In conclusion, this study predicted potential druggable deleterious mutants that can be further explored to understand the pathological basis of cardiovascular disease.
血管紧张素转换酶 1（ACE1）基因在调节血压方面起着关键作用，因此它已成为抗高血压药物的主要治疗靶点。发生在基因内，尤其是在基因功能片段的单核苷酸多态性（SNPs）改变了该基因的结构-功能关系。
我们的研究表明，ACE1 基因的五个 nsSNP 被认为是潜在的有害和破坏性的，包括点突变 P351R、R953Q、I1018T、F1051V 和 T1187M 处的 rs2229839、rs14507892、rs12709442 和 rs4977。蛋白质稳定性预测工具表明，所有的 nsSNP 都降低了蛋白质的稳定性，Consurf 服务器估计蛋白质的进化保守性图谱显示，有三个突变体位于高度保守区域。总之，本研究预测了潜在的可成药有害突变体，可以进一步探索它们，以了解心血管疾病的病理基础。
