Inherited diseases involving g proteins and g protein-coupled receptors

Annu Rev Med. 2004;55:27-39. doi: 10.1146/


Heterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the alpha subunit of the G protein-coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein-coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily ( 1 ). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein-coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease.

Publication types

  • Review

MeSH terms

  • GTP-Binding Proteins / genetics*
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Mutation / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Signal Transduction / genetics*


  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins