The Cyclic Nucleotide Gated Channel Beta 1 (CNGB1) gene codes for one subunit of a rod photoreceptor cGMP-gated cation channel that helps regulate ion flow into photoreceptors of the eye in response to changes in intracellular cGMP in response to light. CNGB1 gene defects cause a type of blindness called retinitis pigmentosa type 45.
GARP2 (glutamic acid-rich protein 2) is an alternate isoform formed by alternative splicing of the CNGB1 transcribed RNARNA. GARP2 is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that regulates spontaneous activation of rod PDE6, lowering ‘dark nose’ and enabling photoreceptors to function at the single photon detection limit. PDE6 are the sixth family of phosphodiesterases of cyclic nucleotides (PDEs). They are photoreceptor-specific PDEs serving as effector enzymes in vertebrate phototransduction.
A frameshift mutation in CNGB1 causing canine progressive retinal atrophy, a condition resembling retinitis pigmentosa, was found in the Papillon dog breeddog breed by two research groups and also in the Phalene dog breed. The first test for the canine mutation was licensed to OptiGen by the research team lead by Simon Petersen-Jones that discovered the CNGB1 mutation in papillon dogs. Gene therapy introducing a normal copy of canine Cngb1a into rod photoreceptors resulted in restoration of rod function and preserved retinal structure in Cngb1-/- dogs.