Membrane proteins are unique in that they interact with lipid bilayers, making them indispensable for transporting molecules and relaying signals between and across cells. Due to the significance of the protein’s functions, mutations often have profound effects on the fitness of the host. This is apparent both from experimental studies, which implicated numerous missense variants in diseases, as well as from evolutionary signals that allow elucidating the physicochemical constraints that intermembrane and aqueous environments bring. In this review, we report on the current state of knowledge acquired on missense variants (referred to as to single amino acid variants) affecting membrane proteins as well as the insights that can be extrapolated from data already available. This includes an overview of the annotations for membrane protein variants that have been collated within databases dedicated to the topic, bioinformatics approaches that leverage evolutionary information in order to shed light on previously uncharacterized membrane protein structures or interaction interfaces, tools for predicting the effects of mutations tailored specifically towards the characteristics of membrane proteins as well as two clinically relevant case studies explaining the implications of mutated membrane proteins in cancer and cardiomyopathy.

中文翻译：

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跨膜蛋白的突变：疾病、进化见解、预测和与球状蛋白的比较。

膜蛋白的独特之处在于它们与脂质双层相互作用，使它们对于在细胞之间和细胞间传递分子和传递信号必不可少。由于蛋白质功能的重要性，突变通常会对宿主的适应性产生深远的影响。这在实验研究中很明显，其中涉及疾病中的许多错义变异，以及允许阐明膜间和水环境带来的物理化学限制的进化信号。在这篇综述中，我们报告了关于影响膜蛋白的错义变体（称为单氨基酸变体）的当前知识状态，以及可以从现有数据中推断出的见解。