Calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a protein kinase that belongs to the serine/threonine kinase family. It phosphorylates kinases like CAMK1, CAMK2, and AMP, and this signaling cascade is involved in various biological processes including cell proliferation, apoptosis, and proliferation. Also, the CAMKK2 signaling activity is required for the healthy activity of the brain which otherwise can cause diseases like bipolar disorders and anxiety. The current study is based on in silico bioinformatics analysis that combines sequence- and structure-based predictions to mark a SNP as damaging or neutral. The combined results from sequence-based, evolutionary conservation-based, and consensus-based tools have predicted a total of 18 nsSNPs as deleterious, and these nsSNPs were further subjected to structure-based analysis. The six mutant models of V195A, V249M, R311C, F366Y, P389T, and W445C showed a higher deviation from the wildtype protein model and hence were further taken for docking studies. The molecular docking analysis has predicted that these mutations will also be disruptive to the protein-protein interactions between CAMKK2 and PRKAG1 which will create an evident reduction in the kinase activity. The current study has enlightened us that a few of the significant mutations are prime candidates in CAMKK2 which could be the fundamental cause of various bipolar and psychiatric disorders. This is the first detailed study that predicts the deleterious nsSNPs in CAMKK2 and contributes positively in providing a better understanding of disease mechanisms.

中文翻译：

---

钙调蛋白依赖性蛋白激酶2（CAMKK2）中的单核苷酸多态性的影响：综合研究。

钙调蛋白依赖性蛋白激酶激酶2（CAMKK2）是属于丝氨酸/苏氨酸激酶家族的蛋白激酶。它使诸如CAMK1，CAMK2和AMP之类的激酶磷酸化，并且这种信号级联反应涉及各种生物学过程，包括细胞增殖，凋亡和增殖。同样，CAMKK2信号传导活性是大脑健康活动所必需的，否则它可能导致疾病如躁郁症和焦虑症。当前的研究基于计算机模拟生物信息学分析，结合基于序列和结构的预测，将SNP标记为破坏性或中性。来自基于序列，基于进化保守性和基于共识的工具的组合结果已预测总共有18个nsSNP有害，并且这些nsSNP还要进行基于结构的分析。V195A，V249M，R311C，F366Y，P389T和W445C的六个突变模型显示出与野生型蛋白质模型的更高偏差，因此被进一步用于对接研究。分子对接分析已预测，这些突变也将破坏CAMKK2和PRKAG1之间的蛋白质相互作用，从而明显降低激酶活性。当前的研究启发了我们，CAMKK2中的一些重要突变是主要候选基因，这可能是导致各种躁郁症和精神病的根本原因。这是第一项详细的研究，其预测CAMKK2中的有害nsSNP，并有助于更好地理解疾病机理。