Rod-specific cGMP phosphodiesterase 6 subunit beta (PDE6B)

Rod-specific cGMP phosphodiesterase 6 subunit beta (PDE6B) is a critical enzyme located in the outer segments of rod photoreceptor cells, where it plays a central role in the vertebrate visual phototransduction cascade (UniProt P35913). Upon activation by transducin in response to light, the PDE6 holoenzyme—composed of alpha, beta, and two gamma subunits—hydrolyzes cyclic guanosine monophosphate (cGMP), leading to the closure of cyclic nucleotide-gated (CNG) channels and subsequent cell hyperpolarization (PubMed 28826534). Mutations in the PDE6B gene locus result in a loss of enzymatic activity, leading to toxic accumulation of cGMP and calcium, which causes the progressive degeneration of rod photoreceptors (NCBI Gene 5158). This genetic defect is a primary cause of autosomal recessive retinitis pigmentosa (RP40) and congenital stationary night blindness. Current therapeutic development focuses on gene augmentation therapy, such as COAVE-PDE6B, which utilizes adeno-associated virus (AAV) vectors to deliver a functional copy of the PDE6B gene directly to the retina to restore phototransduction and preserve visual function (Coave Therapeutics, 2023).

Other names

PDEBRP40CSNB3CSNBAD2Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit betaGMP-PDE beta

Gene augmentation therapy