Wilson disease (WD), a Mendelian disorder of copper metabolism caused by mutations in the ATP7B gene, manifests a large spectrum of phenotypic variability. This phenomenon of extensive symptom variation is not frequently associated with a monogenic disorder. We hypothesize that the phenotypic variability in WD is primarily driven by the variations in interacting proteins that regulate the ATP7B function and localization in the cell. Based on existing literature, we delineated a potential molecular mechanism for ATP7B mediated copper transport in the milieu of its interactome, its dysfunction in WD and the resulting variability in the phenotypic manifestation. Understanding the copper-induced apical trafficking of ATP7B also significantly contributes to the appreciation of the complexities of the ligand-induced transport pathway. We believe that this holistic view of WD will pave the way for a better opportunity for rational drug design and therapeutics.

中文翻译：

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威尔逊病蛋白ATP7B的调控一瞥，揭示了哺乳动物根尖运输途径的复杂性

威尔逊病（WD），一种由ATP7B突变引起的孟德尔铜代谢紊乱基因，表现出大范围的表型变异。这种症状广泛变化的现象通常不与单基因疾病相关。我们假设WD的表型变异性主要是由调节ATP7B功能和细胞内定位的相互作用蛋白的变异所驱动。根据现有文献，我们描述了ATP7B介导的铜在其相互作用基因组环境中的潜在分子机制，其在WD中的功能障碍以及由此产生的表型表现变异。了解铜诱导的ATP7B的顶端运输也极大地有助于理解配体诱导的运输途径的复杂性。