Cyclic nucleotide-gated channel alpha 3 (CNGA3) (CNGA3)

Cyclic nucleotide-gated channel alpha 3 (CNGA3) is a critical component of the ion channels found in the outer segments of cone photoreceptors in the retina (UniProt P29973). It functions as a cyclic nucleotide-gated cation channel that opens in response to high levels of cGMP in the dark, allowing the influx of sodium and calcium ions to depolarize the cell (NCBI Gene 1261). Upon light stimulation, cGMP levels drop, causing the channel to close and the cell to hyperpolarize, which is a fundamental step in the visual phototransduction cascade (PubMed PMID: 10958725). Mutations in the CNGA3 gene are a leading cause of achromatopsia, an inherited condition resulting in the loss of cone function, leading to total color blindness and poor visual acuity (PubMed PMID: 25855487). Current therapeutic development is heavily focused on adeno-associated virus (AAV)-based gene therapies, such as AGTC-401, designed to deliver a functional CNGA3 gene to the retina to restore cone-mediated vision (ClinicalTrials.gov NCT02599922). These therapies aim to provide long-term expression of the functional protein, potentially halting or reversing the visual deficits associated with the disease (PubMed PMID: 32350125).

Other names

Cyclic nucleotide-gated cation channel alpha-3Cone photoreceptor cGMP-gated channel subunit alphaCCNC1ACHM2CNG3

Gene replacement therapy to restore functional CNGA3 protein in cone photoreceptors.