Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A) (PDE6A)

The PDE6A gene encodes the alpha subunit of the rod-specific cyclic GMP (cGMP) phosphodiesterase, a critical enzyme located in the outer segments of rod photoreceptor cells. This enzyme is a central component of the visual phototransduction cascade, where it hydrolyzes cGMP in response to light activation, leading to the closure of cGMP-gated cation channels and subsequent cell hyperpolarization (UniProt P16499). Mutations in PDE6A result in a lack of functional PDE6 enzyme, causing an abnormal accumulation of cGMP and calcium that is toxic to rod cells, eventually leading to their degeneration (NCBI Gene 5145). This process manifests clinically as Retinitis Pigmentosa 43, characterized by progressive night blindness and loss of peripheral vision (OMIM 180071). Current therapeutic development focuses on gene replacement therapy, such as COAV-101, which utilizes adeno-associated virus (AAV) vectors to deliver a functional copy of the PDE6A gene directly to the retina (Coave Therapeutics). These treatments aim to halt the progression of retinal degeneration and preserve remaining vision in patients with confirmed biallelic PDE6A mutations.

Other names

Phosphodiesterase 6AGMP-PDE alphaCGPR-APDEVPDEA

Gene replacement therapy via adeno-associated virus (AAV) vector to restore functional PDE6A enzyme activity in rod photoreceptors.