FAM20C(具有序列相似性的家族,成员C)是一种丝氨酸/苏氨酸特异性蛋白激酶,其广泛表达并且主要与生物矿化和磷酸盐血症调节相关。它主要是由于致病变异导致其缺乏而已知的,导致雷恩综合征(RNS),伴有低磷酸盐血症的硬化性骨发育不良。表型由骨骼特征识别,这与不同FAM20C骨靶蛋白的低磷酸化有关。然而,FAM20C有很多目标,包括脑蛋白和脑脊液磷酸蛋白质组。患有RNS的人可能有发育迟缓,智力残疾,癫痫发作,和脑结构性缺陷,但对FAM20C脑靶蛋白失调或与神经系统特征相关的潜在发病机制知之甚少。为了识别FAM20C对大脑的潜在作用,进行了计算机模拟分析。描述了RNS中报告的结构和功能缺陷;确定了FAM20C靶标和相互作用者,包括他们的大脑表情。分子过程的基因本体论,函数,这些目标的组件已经完成,以及潜在涉及的信号通路和疾病。BioGRID和人类蛋白质图谱数据库,大猩猩的工具,并使用了PANTHER和DisGeNet数据库。结果表明,脑中高表达的基因参与胆固醇和脂蛋白过程,加上轴突-树突运输和神经元部分。这些结果可能突出了一些与RNS的神经发病机制有关的蛋白质。
FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different
FAM20C bone-target proteins. However,
FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential
FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described;
FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.