Genetic diseases associated with heterotrimeric G proteins.
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 betagamma dimer. Several human disorders that result from genetic G-protein abnormalities involve the imprinted GNAS gene, which encodes Gs 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 Gbeta3) 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.
Weinstein
Lee S
LS
Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. leew@amb.niddk.nih.gov
Chen
Min
M
Xie
Tao
T
Liu
Jie
J
D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000503:physiopathology; D020962:Heterotrimeric GTP-Binding Proteins / Q000009:adverse effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008967:Molecular Biology / Q000639:trends*; D009154:Mutation; D011110:Polymorphism, Genetic; D015293:Transducin
D002864:Chromogranins; C034809:GNAT1 protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin