Genetic diseases associated with heterotrimeric G proteins

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tips.2006.03.005 Byline: Lee S. Weinstein, Min Chen, Tao Xie, Jie Liu Abstract: Heterotrimeric G proteins couple receptors for diverse extracellular signals to effector enzymes or ion channels. Each G protein comprises a specific [alpha]-subunit and a tightly bound [beta][gamma] dimer. Several human disorders that result from genetic G-protein abnormalities involve the imprinted GNAS gene, which encodes G.sub.s[alpha], the ubiquitously expressed [alpha]-subunit that couples receptors to adenylyl cyclase and cAMP generation. Loss-of-function and gain-of-function mutations, in addition to imprinting defects, of this gene lead to diverse clinical phenotypes. Mutations of GNAT1 and GNAT2, which encode the retinal G proteins (transducins), are rare causes of specific congenital visual defects. Common polymorphisms of the GNAS and GNB3 (which encodes G[beta].sub.3) genes have been associated with multigenic disorders (e.g. hypertension and metabolic syndrome). To date, no other G proteins have been implicated directly in human disease. Author Affiliation: Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA