The CNGA3 gene (Cyclic Nucleotide Gated Channel, Alpha-3) gene codes for the alpha-subunit of the cGMP gated cation (CNG) channel in human cone photoreceptors. Functional cGMP cation channels are heteromeric, composed of two alpha and two beta subunits. These CNG channels are the final critical effectors of the phototransduction cascade. In the dark, with high cGMP levels in the cone cells, cGMP binds to the CNG channels, in effect 'opening' these channels, and permitting an influx of cations that cause a depolarization of the cones. In the presence of light, cGMP levels are lowered, resulting in the closure of these channels, and consequent cone hyperpolarization.
Orthologous CNGA3 knockout mice show complete absence of physiologically measurable cone function, a decrease in the number of cones in the retina, and morphologic abnormalities of the remaining cones. In humans, mutations in CNGA3 result in achromatopsia, a congenital disorder characterized by a complete absence of functional cones in the retina, and accompanied by other visual defects like photophobia and nystagmus.