CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors. It is a key gene in the cone phototransduction cascade, which is crucial for high-acuity daylight vision and color discrimination [1,4,6]. Mutations in CNGA3 are associated with several retinal disorders, most notably achromatopsia (ACHM), a congenital cone photoreceptor disorder [1,2,3,4,6].

In ACHM patients, a comprehensive study of 1060 genetically confirmed cases found that 36.3% carried "likely disease-causing" variants in CNGA3. Compiling data, the CNGA3 variant spectrum was extended to 316 variants, with 244 interpreted as "likely disease-causing" according to ACMG/AMP criteria. 48 novel "likely disease-causing" variants were reported, many being missense substitutions [1]. Functional analyses of CNGA3 splice and missense variants have been conducted to better classify their pathogenicity, which is important for diagnosis and potential gene-based therapeutic strategies [7,8]. Gene therapy trials for CNGA3-linked ACHM are in progress, with preclinical studies in Cnga3-/-mouse models showing partial restoration of cone electrophysiology and integration of new photopic vision in tests, indicating the potential of gene therapy if applied early in childhood [3,5].

In conclusion, CNGA3 is essential for cone photoreceptor function and normal vision. Research on CNGA3, especially through gene knockout mouse models, has significantly advanced our understanding of its role in ACHM. The findings from these models have paved the way for gene therapy development, offering hope for treating CNGA3-related retinal diseases.