Functional evidence for a few coding variants was reported. The 118A>G SNP was the first variant that was shown to be functional by the combined groups of Kreek and Yu (Bond et al. 1998) (see section below). Three rare SNPs in highly evolutionary conserved amino acids 779G>A (Arg260His), 794G>A (Arg265His), and 802T>C (Ser268Pro) in the third intracellular loop of the receptor were shown to decrease receptor signaling activity (Befort et al. 2001; Wang et al. 2001). SNP 802T>C was also shown to lose Ca2+/calmodulin-dependent protein kinase-induced receptor desensitization (Koch et al. 2000).
