Mutations in G Protein–Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches,Pharmacological Reviews

当前位置： X-MOL 学术 › Pharmacol. Rev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Mutations in G Protein–Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2021-01-01 , DOI: 10.1124/pharmrev.120.000011
Torsten Schöneberg ₁ , Ines Liebscher ₂

Affiliation

There are approximately 800 annotated G protein–coupled receptor (GPCR) genes, making these membrane receptors members of the most abundant gene family in the human genome. Besides being involved in manifold physiologic functions and serving as important pharmacotherapeutic targets, mutations in 55 GPCR genes cause about 66 inherited monogenic diseases in humans. Alterations of nine GPCR genes are causatively involved in inherited digenic diseases. In addition to classic gain- and loss-of-function variants, other aspects, such as biased signaling, trans-signaling, ectopic expression, allele variants of GPCRs, pseudogenes, gene fusion, and gene dosage, contribute to the repertoire of GPCR dysfunctions. However, the spectrum of alterations and GPCR involvement is probably much larger because an additional 91 GPCR genes contain homozygous or hemizygous loss-of-function mutations in human individuals with currently unidentified phenotypes. This review highlights the complexity of genomic alteration of GPCR genes as well as their functional consequences and discusses derived therapeutic approaches.

中文翻译：

G 蛋白偶联受体的突变：机制、病理生理学和潜在的治疗方法

大约有 800 个带注释的 G 蛋白偶联受体 (GPCR) 基因，使这些膜受体成为人类基因组中最丰富的基因家族的成员。除了参与多种生理功能并作为重要的药物治疗靶点外，55 个 GPCR 基因的突变会导致人类约 66 种遗传性单基因疾病。九个 GPCR 基因的改变与遗传性双基因疾病有关。除了经典的增益和功能损失变体之外，其他方面，例如偏置信号、反式- 信号传导、异位表达、GPCR 的等位基因变体、假基因、基因融合和基因剂量，都会导致 GPCR 功能障碍。然而，改变和 GPCR 参与的范围可能要大得多，因为另外 91 个 GPCR 基因在人类个体中包含纯合或半合的功能丧失突变，目前尚未确定表型。这篇综述强调了 GPCR 基因基因组改变的复杂性及其功能后果，并讨论了衍生的治疗方法。

更新日期：2020-11-21

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11