GUCY2F

GUCY2F is a human gene that encodes for guanylate cyclase 2F, also known as retinal guanylyl cyclase 2 (retGC2). GUCY2F is a member of the guanylate cyclase family, a group of enzymes that catalyze the synthesis of cyclic GMP (cGMP) from GTP and regulate a variety of physiological processes.

Function:

The protein encoded by GUCY2F, retGC2, is primarily expressed in photoreceptor cells (rods and cones) of the retina. It plays a critical role in visual phototransduction, the process by which light is converted into electrical signals that are sent to the brain. In the dark, retGC2 maintains a high level of cGMP. When light strikes rhodopsin (in rods) or cone opsins (in cones), a cascade of events leads to the activation of phosphodiesterase 6 (PDE6), which hydrolyzes cGMP. The decrease in cGMP concentration causes cyclic nucleotide-gated (CNG) channels to close, hyperpolarizing the photoreceptor cell and triggering the signal. RetGC2 is then activated by guanylate cyclase-activating proteins (GCAPs) in response to decreasing calcium levels, replenishing cGMP and restoring the photoreceptor to its dark state.

Clinical Significance:

Mutations in the GUCY2F gene have been associated with several inherited retinal diseases, including:

• Cone-rod dystrophy (CORD): A progressive degeneration of both cone and rod photoreceptors, leading to impaired color vision, reduced visual acuity, and eventual blindness.
• Leber congenital amaurosis (LCA): A severe form of inherited retinal dystrophy that causes profound visual impairment from birth or early infancy.

The specific mutations in GUCY2F and their location within the gene can influence the severity and phenotype of the associated retinal disease. Genetic testing for GUCY2F mutations is often used in the diagnosis and management of patients with suspected inherited retinal dystrophies.

Further Research:

Ongoing research is focused on understanding the detailed mechanisms of retGC2 regulation and the pathogenic effects of different GUCY2F mutations. This knowledge is crucial for developing potential therapies, such as gene therapy or pharmacological interventions, to treat or prevent vision loss associated with GUCY2F-related retinal diseases.