Exon Sequencing of G Protein-Coupled Receptor Genes and Perspectives for Disease Treatment

G protein-coupled receptors (GPCRs) comprise the largest family of membrane-spanning proteins in humans with approximately 800 members. GPCRs carry out an extensive array of biological functions and are privileged drug targets. Exon sequencing identified several disease-causing loss-of-function and gain-of-function GPCR mutations in patients with rare diseases. Recent large-scale exon sequencing studies revealed the high abundance of rare GPCR mutations in the human population. Many of these rare mutations are suspected to contribute to the risk of common diseases and interindividual and ethnic differences in drug action. Functional profiling of a large number of GPCR mutants will be necessary to identify those mutants with modified function. Defining the functional defects in carriers of rare GPCR mutations will help to provide refined and personalized therapies to these patients in the future. The impact of GPCR mutations in rare and common diseases will be discussed in this review based on specific examples.