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

Cyclic nucleotide-gated channel subunit alpha-3 (CNGA3) is a critical component of the ion channels located in the outer segments of cone photoreceptors in the retina [1]. It forms a functional heterotetrameric channel with the CNGB3 subunit, which opens in response to cyclic guanosine monophosphate (cGMP) to allow the influx of sodium and calcium ions, a process essential for phototransduction under daylight conditions [1, 2]. Mutations in the CNGA3 gene are a primary cause of achromatopsia, a rare autosomal recessive disorder characterized by a complete lack of color vision, low visual acuity, and extreme light sensitivity [3]. Because the loss of CNGA3 function leads to the dysfunction and eventual degeneration of cone cells, it has become a major target for regenerative medicine and gene therapy [4]. Current therapeutic strategies primarily focus on adeno-associated virus (AAV)-mediated gene therapy designed to deliver a functional copy of the CNGA3 gene to the cone cells [3, 4]. Clinical trials are currently evaluating the safety and efficacy of these gene replacement therapies, such as AGTC-401, in restoring cone function and improving visual outcomes for patients with achromatopsia [4, 5]. Sources: [1] UniProt Consortium. (2023). P29973 · CNGA3_HUMAN. https://www.uniprot.org/uniprotkb/P29973/entry [2] NCBI Gene. (2024). CNGA3 cyclic nucleotide gated channel subunit alpha 3 [Homo sapiens]. https://www.ncbi.nlm.nih.gov/gene/1259 [3] Michalakis, S., et al. (2022). Gene Therapy for CNGA3-Linked Achromatopsia. Frontiers in Molecular Neuroscience. https://doi.org/10.3389/fnmol.2021.799662 [4] ClinicalTrials.gov. (2023). Safety and Efficacy of AGTC-401 in Patients With Achromatopsia Caused by Mutations in the CNGA3 Gene. https://clinicaltrials.gov/ct2/show/NCT02599922 [5] Reichel, F. F., et al. (2020). Three-Year Results of Phase 1/2 Gene Therapy Trial for CNGA3-Linked Achromatopsia. JAMA Ophthalmology. https://doi.org/10.1001/jamaophthalmol.2020.3656

Other names

ACHM2CCNC1CNCG3Cone photoreceptor cGMP-gated channel subunit alpha

Gene replacement therapy via viral vector delivery to restore functional cone photoreceptor cyclic nucleotide-gated channels [3, 4].