| Gene (HGNC symbol) | Protein/function in cone | Pathway step (phototransduction/CNG/UPR) | Typical inheritance | Relative contribution/proportion if stated in evidence | Notes on phenotype (complete vs incomplete; progression) | Key sources (with URL/year) |
|---|---|---|---|---|---|---|
| **CNGA3** | Alpha subunit of the cone cyclic nucleotide-gated (CNG) channel; part of the final step converting cGMP changes into cone electrical responses (pqac-00000003, pqac-00000033, pqac-00000036) | **CNG / cone phototransduction** | Autosomal recessive (pqac-00000003, pqac-00000004) | Together with **CNGB3**, accounts for **up to ~90%** of ACHM; older review gives CNGA3 alone **~25%** (pqac-00000003, pqac-00000004, pqac-00000005) | Can cause complete or incomplete ACHM; incomplete forms reported particularly with some missense variants in CNGA3; no strong genotype-phenotype correlation overall; progression less commonly documented than for CNGB3/PDE6C in Danish cohort (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000014) | Baxter & Borchert 2024, https://doi.org/10.3390/ijms25179739 (2024); Michalakis et al. 2022, https://doi.org/10.1007/s40291-021-00565-z (2022); Gerhardt et al. 2023, https://doi.org/10.3390/biomedicines11020269 (2023) (pqac-00000003, pqac-00000004, pqac-00000035) |
| **CNGB3** | Beta subunit of the cone CNG channel; required with CNGA3 for functional cone CNG channel assembly and normal cone responses (pqac-00000003, pqac-00000030, pqac-00000034) | **CNG / cone phototransduction** | Autosomal recessive (pqac-00000003, pqac-00000004) | Together with **CNGA3**, **up to ~90%** of ACHM; older review gives CNGB3 alone **~50%** of autosomal recessive ACHM (pqac-00000003, pqac-00000004, pqac-00000008) | Often associated with **complete achromatopsia** in review evidence; progressive BCVA deterioration attributable to ACHM was observed in some CNGB3 patients in long-term Danish follow-up (pqac-00000001, pqac-00000002, pqac-00000014) | Baxter & Borchert 2024, https://doi.org/10.3390/ijms25179739 (2024); Michalakis et al. 2022, https://doi.org/10.1007/s40291-021-00565-z (2022); Asensio-Sánchez 2020 (pqac-00000003, pqac-00000004, pqac-00000008) |
| **GNAT2** | Cone transducin alpha subunit; couples activated cone opsin to PDE activation in phototransduction (pqac-00000003, pqac-00000032, pqac-00000033) | **Phototransduction** | Autosomal recessive (disease-level ACHM inheritance) (pqac-00000003, pqac-00000004) | Rare; older review states **<2%** (pqac-00000005) | Missense GNAT2 variants have been associated with **incomplete achromatopsia** and relative preservation of cone structure/function in some reports; Danish cohort suggested myopia may be more frequent with GNAT2 and no BCVA deterioration was reported in that cohort subset (pqac-00000001, pqac-00000014, pqac-00000032) | Baxter & Borchert 2024, https://doi.org/10.3390/ijms25179739 (2024); Yang et al. 2024, https://doi.org/10.3389/fnins.2024.1265630 (2024); Asensio-Sánchez 2020 (pqac-00000003, pqac-00000032, pqac-00000005) |
| **PDE6C** | Cone phosphodiesterase catalytic subunit; hydrolyzes cGMP in response to transducin activation (pqac-00000003, pqac-00000031, pqac-00000033) | **Phototransduction / cGMP metabolism** | Autosomal recessive (disease-level ACHM inheritance) (pqac-00000003, pqac-00000004) | Rare; older review states **<2%** (pqac-00000005) | Missense PDE6C variants can be associated with **incomplete ACHM** in review evidence, but PDE6C is also linked to more progressive cone disease in some reports; Danish cohort found progression attributable to ACHM in PDE6C and more frequent myopia/severe myopia (pqac-00000001, pqac-00000002, pqac-00000014, pqac-00000032) | Baxter & Borchert 2024, https://doi.org/10.3390/ijms25179739 (2024); Yang et al. 2024, https://doi.org/10.3389/fnins.2024.1265630 (2024); Nouri et al. 2024, https://doi.org/10.1186/s12920-024-01942-3 (2024) (pqac-00000003, pqac-00000031) |
| **PDE6H** | Cone phosphodiesterase gamma/inhibitory subunit; regulates cone PDE activity and therefore cGMP levels (pqac-00000003, pqac-00000031, pqac-00000032) | **Phototransduction / cGMP metabolism** | Autosomal recessive (disease-level ACHM inheritance) (pqac-00000003, pqac-00000004) | Very rare; older review states **<1%** (pqac-00000005) | Missense PDE6H variants have been associated with **incomplete achromatopsia** in review evidence; Danish cohort found no BCVA deterioration in PDE6H subset but a high proportion with myopia/severe myopia (pqac-00000001, pqac-00000014, pqac-00000031) | Baxter & Borchert 2024, https://doi.org/10.3390/ijms25179739 (2024); Yang et al. 2024, https://doi.org/10.3389/fnins.2024.1265630 (2024); Asensio-Sánchez 2020 (pqac-00000003, pqac-00000031, pqac-00000005) |
| **ATF6** | Activating transcription factor 6; ER membrane transcription factor regulating unfolded protein response and essential for human cone photoreceptor development (pqac-00000030, pqac-00000031) | **UPR / ER homeostasis / cone development** | Autosomal recessive (disease-level ACHM inheritance) (pqac-00000003, pqac-00000004) | Rare; older review states **~1–2%** (pqac-00000005) | Mechanistically distinct from phototransduction genes; associated with developmental cone defects and foveal hypoplasia/absence of cone structures rather than only signaling failure; may provide fewer residual cone targets for classic gene replacement; pharmacologic ATF6 activation has shown rescue of cone growth/gene expression in patient organoids (pqac-00000031, pqac-00000032) | Kroeger et al. 2021, https://doi.org/10.1073/pnas.2103196118 (2021); Michalakis et al. 2022, https://doi.org/10.1007/s40291-021-00565-z (2022); Yang et al. 2024, https://doi.org/10.3389/fnins.2024.1265630 (2024) (pqac-00000030, pqac-00000031) |


*Table: This table summarizes the established achromatopsia genes, their functional roles in cone biology, and evidence-based phenotype notes. It is useful for linking genotype to mechanism, inheritance, and expected clinical presentation.*