ClinVar

In a family with autosomal dominant retinitis pigmentosa (RP4; 613731), Keen et al. (1991) observed change in codon 296 from AAG to GAG resulting in substitution of glutamic acid for lysine. The disorder in this family was distinguished by its particular severity, showing early onset of the disease and development of cataracts by the third or fourth decade of life. Two critical amino acids in rhodopsin are lys296, the site of attachment of retinal to the protein through a protonated Schiff base linkage, and glu113, the Schiff base counterion. Robinson et al. (1992) demonstrated that mutation in lys296 or in glu113 results in constitutive activation of opsin, as assayed by its ability to activate the G protein transducin in the absence of added chromophore. They concluded that opsin is constrained to an inactive conformation by a salt bridge between lys296 and glu113. The lys296-to-glu (K296E) mutation in the family reported by Keen et al. (1991) may represent degeneration of the photoreceptor cells as a result of persistent stimulation of the phototransduction pathway.