Distinct cellular mechanisms of GPCR mutations implicated in human diseases (6–8).
| Loss-of-function mutations | Gain-of-function mutations |
| Decrease in binding affinity | Constitutively (signaling activity in the absence of agonist) |
| Abnormal receptor trafficking | Nonconstitutively |
| Decrease of signaling activity | Promiscuous activation (exclusive of the glycoprotein receptors) |
| Multiple effects |