GNAS复合轨迹
异三聚体G蛋白
表观遗传学
G蛋白偶联受体
生物
黑素皮质素4受体
Gsα亚单位
内分泌学
内科学
假性甲状旁腺机能减退
生物信息学
遗传学
G蛋白
医学
受体
基因
激素
黑素皮质素
甲状旁腺激素
钙
作者
Alaa A. Abbas,Ayat S. Hammad,Mashael Al-Shafai
标识
DOI:10.1016/j.mrrev.2023.108487
摘要
GNAS (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes Gsα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homeostasis, and body weight. Genetic or epigenetic alterations in GNAS are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity. Given the diverse biological functions that Gsα serves, multiple molecular mechanisms involving various GPCRs, such as MC4R, β2- and β3-adrenoceptors, and corticotropin-releasing hormone receptor, have been implicated in the pathophysiology of severe, early-onset obesity that results from genetic or epigenetic GNAS changes. This review examines the structure and function of GNAS and provides an overview of the disorders that are caused by defects in this gene and may feature early-onset obesity. Moreover, it elucidates the potential molecular mechanisms underlying Gsα deficiency-induced early-onset obesity, highlighting some of their implications for the diagnosis, management, and treatment of this complex condition. Gsα deficiency is an underappreciated cause of early-onset, severe obesity. Therefore, screening children with unexplained, severe obesity for GNAS defects is recommended, to enhance the molecular diagnosis and management of this condition.
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