text: Loss of function mutations have been shown in a number of adhesion GPCRs, including GPR56, GPR126 and VLRG1.  Many mutations affect function via decreased cell surface expression or inhibition of autoproteolysis within the GAIN domain. 
  Mutations in GPR56 result in bilateral frontoparietal polymicrogyria in humans, characterized by abnormal neuronal migration and surface ectopias., Variants of GPR126 have been associated with adolescent idiopathic scoliosis, as well as  being responsible for severe arthrogryposis multiplex congenita.  Gain of function mutations within the GAIN domain of EMR2 have been shown to result in excessive degranulation by mast cells resulting in vibratory urticaria.