Table 1

Distinct cellular mechanisms of GPCR mutations implicated in human diseases (68).

Loss-of-function mutationsGain-of-function mutations
Decrease in binding affinityConstitutively (signaling activity in the absence of agonist)
Abnormal receptor traffickingNonconstitutively
Decrease of signaling activityPromiscuous activation (exclusive of the glycoprotein receptors)
Multiple effects