G protein-coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e., in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. The discovery of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation drew attention to the evolving area of GPCR pharmacogenomics. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring, constitutively active GPCR variants linked to disease. In this review, we provide a brief historical introduction to the concept of constitutive receptor activity and the pharmacogenomic and structural aspects of constitutive receptor activity.

中文翻译：

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组成型g蛋白偶联受体活性的药物基因组和结构分析。

G蛋白偶联受体（GPCR）响应化学上过多的信号转导分子。GPCR在没有外部化学触发的情况下（即以组成性或自发性方式）也发出信号的概念导致GPCR药理学领域的范式转移。组成性GPCR活性的发现以及单点突变会严重影响GPCR结合和信号转导的事实，引起人们对GPCR药物基因组学不断发展的领域的关注。对于各种GPCR，点突变已令人信服地与人类疾病联系在一起。已知与GPCR活化有关的保守基序内的突变，可能解释了与疾病相关的某些天然存在的，组成性活跃的GPCR变体的特性。在这篇评论中