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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CNGA3
cyclic nucleotide gated channel subunit alpha 3
Chromosome 2 Β· 2q11.2
NCBI Gene: 1261Ensembl: ENSG00000144191.13HGNC: HGNC:2150UniProt: Q16281
79PubMed Papers
21Diseases
0Drugs
224Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
intracellularly cGMP-activated cation channel activityprotein bindingplasma membranemonoatomic cation transportachromatopsiaachromatopsia 2Retinal dystrophyCone rod dystrophy
✦AI Summary

CNGA3 encodes the pore-forming alpha subunit of the cone cyclic nucleotide-gated (CNG) channel, essential for phototransduction in bright light conditions 1. In darkness, high cGMP levels keep the channel open, allowing inward current from Na+ and Ca2+ ions that depolarizes cone photoreceptor membranes and enables neurotransmitter release 1. Upon photon absorption, cGMP levels decline, closing the channel and hyperpolarizing the membrane, thereby signaling light detection 1. CNGA3 also functions in gustatory CNG channels where it may sense oral pH and modulate taste cell excitability 1. Pathogenic CNGA3 variants cause achromatopsia, an autosomal recessive cone dysfunction syndrome affecting 1 in 30,000 individuals 2. Up to 90% of achromatopsia patients carry CNGA3 or CNGB3 mutations 1. Disease manifests at birth or early infancy with poor visual acuity, nystagmus, photophobia, and complete color vision loss due to cone photoreceptor dysfunction and slow progressive degeneration 1. No FDA-approved therapy currently exists 2. However, preclinical studies demonstrate that intravitreal adeno-associated virus (AAV) gene therapy delivering CNGA3 achieves cone-specific protein expression and rescues photopic cone responses in animal models 3. Multiple phase I/II clinical trials for CNGA3-linked achromatopsia are registered, offering potential therapeutic hope for affected patients 2.

Sources cited
1
CNGA3 encodes the alpha subunit of cone CNG channel; phototransduction mechanism in darkness and light; disease manifestation and cone degeneration
PMID: 34860352
2
Achromatopsia prevalence, inheritance pattern, CNGA3 mutation frequency, clinical presentation, and current status of clinical trials
PMID: 39273686
3
AAV2.GL-mediated intravitreal CNGA3 gene therapy achieves cone-specific expression and rescues photopic responses in Cnga3-/- mouse model
PMID: 33616280
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
achromatopsiaOpen Targets
0.83Strong
achromatopsia 2Open Targets
0.71Strong
Retinal dystrophyOpen Targets
0.57Moderate
Cone rod dystrophyOpen Targets
0.54Moderate
cone-rod dystrophyOpen Targets
0.54Moderate
CNGA3-related retinopathyOpen Targets
0.49Moderate
cone dystrophyOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.47Moderate
Abnormality of the eyeOpen Targets
0.43Moderate
Rod-cone dystrophyOpen Targets
0.38Weak
eye diseaseOpen Targets
0.37Weak
optic atrophyOpen Targets
0.34Weak
MonochromacyOpen Targets
0.33Weak
achromatopsia 3Open Targets
0.33Weak
ovarian dysfunctionOpen Targets
0.33Weak
retinopathyOpen Targets
0.30Weak
Precordial painOpen Targets
0.29Weak
device complicationOpen Targets
0.28Weak
PhotophobiaOpen Targets
0.27Weak
Color vision defectOpen Targets
0.27Weak
Achromatopsia 2UniProt
Pathogenic Variants224
NM_001298.3(CNGA3):c.1279C>T (p.Arg427Cys)Pathogenic
Achromatopsia|not provided|Macular dystrophy|Retinal dystrophy|Achromatopsia 2|Abnormality of the eye
β˜…β˜…β˜†β˜†2026β†’ Residue 427
NM_001298.3(CNGA3):c.1021T>C (p.Ser341Pro)Pathogenic
Retinal dystrophy|not provided|Achromatopsia 2
β˜…β˜…β˜†β˜†2026β†’ Residue 341
NM_001298.3(CNGA3):c.848G>A (p.Arg283Gln)Pathogenic
Achromatopsia 2|not provided|Retinal dystrophy|Achromatopsia
β˜…β˜…β˜†β˜†2026β†’ Residue 283
NM_001298.3(CNGA3):c.1315C>T (p.Arg439Trp)Pathogenic
not provided|Retinal dystrophy|Achromatopsia 2|Achromatopsia 3
β˜…β˜…β˜†β˜†2026β†’ Residue 439
NM_001298.3(CNGA3):c.822G>T (p.Arg274Ser)Pathogenic
Achromatopsia 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 274
NM_001298.3(CNGA3):c.1706G>A (p.Arg569His)Pathogenic
not provided|Retinal dystrophy|Achromatopsia 2
β˜…β˜…β˜†β˜†2026β†’ Residue 569
NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln)Pathogenic
Retinal dystrophy|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 223
NM_001298.3(CNGA3):c.488C>T (p.Pro163Leu)Pathogenic
Achromatopsia 2|Retinal dystrophy|Achromatopsia
β˜…β˜…β˜†β˜†2026β†’ Residue 163
NM_001298.3(CNGA3):c.450-1G>APathogenic
not provided|Achromatopsia 2|CNGA3-related disorder
β˜…β˜…β˜†β˜†2026
NM_001298.3(CNGA3):c.829C>T (p.Arg277Cys)Pathogenic
Achromatopsia 2|Achromatopsia|Color vision defect;Macular degeneration;Photophobia|not provided|Retinal dystrophy|Optic atrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 277
NM_001298.3(CNGA3):c.934ATC[2] (p.Ile314del)Pathogenic
Achromatopsia|not provided|Retinal dystrophy|Achromatopsia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 314
NM_001298.3(CNGA3):c.1688G>A (p.Arg563His)Pathogenic
not provided|Abnormality of the eye|Retinal dystrophy|Achromatopsia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 563
NM_001298.3(CNGA3):c.830G>A (p.Arg277His)Pathogenic
Achromatopsia 2|not provided|Retinal dystrophy|Achromatopsia
β˜…β˜…β˜†β˜†2025β†’ Residue 277
NM_001298.3(CNGA3):c.396-11C>GPathogenic
not provided|Achromatopsia 2
β˜…β˜…β˜†β˜†2025
NM_001298.3(CNGA3):c.661C>T (p.Arg221Ter)Pathogenic
not provided|Achromatopsia 2|Retinal disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 221
NM_001298.3(CNGA3):c.1585G>A (p.Val529Met)Pathogenic
Achromatopsia 2|not provided|Achromatopsia|CNGA3-related retinopathy|CNGA3-related disorder|Retinal dystrophy|Achromatopsia 3
β˜…β˜…β˜†β˜†2025β†’ Residue 529
NM_001298.3(CNGA3):c.955T>C (p.Cys319Arg)Pathogenic
not provided|Achromatopsia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 319
NM_001298.3(CNGA3):c.1641C>A (p.Phe547Leu)Pathogenic
Achromatopsia 2|Monochromacy|not provided|Achromatopsia|Retinal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 547
NM_001298.3(CNGA3):c.1565T>C (p.Ile522Thr)Pathogenic
not provided|Achromatopsia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 522
NM_001298.3(CNGA3):c.1114C>T (p.Pro372Ser)Pathogenic
Achromatopsia|not provided|Achromatopsia 2|CNGA3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 372
View on ClinVar β†—
Related Genes
RHOProtein interaction100%CNGA4Protein interaction100%PDE6AProtein interaction98%OPN4Protein interaction91%RPE65Protein interaction88%GNAT1Protein interaction88%
Tissue Expression6 tissues
Brain
100%
Lung
1%
Bone Marrow
1%
Ovary
0%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CNGA3RHOCNGA4PDE6AOPN4RPE65GNAT1
PROTEIN STRUCTURE
Preparing viewer…
PDB3SWY Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.13LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.88 [0.69–1.13]
RankingsWhere CNGA3 stands among ~20K protein-coding genes
  • #5,985of 20,598
    Most Researched79
  • #293of 5,498
    Most Pathogenic Variants224 Β· top 10%
  • #11,632of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedCNGA3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Achromatopsia: Genetics and Gene Therapy.
PMID: 34860352
Mol Diagn Ther Β· 2022
1.00
2
Gene Therapy for Achromatopsia.
PMID: 39273686
Int J Mol Sci Β· 2024
0.90
3
Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders.
PMID: 33616280
EMBO Mol Med Β· 2021
0.80
4
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
PMID: 38278208
Prog Retin Eye Res Β· 2024
0.70
5
A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).
PMID: 31456290
Hum Mutat Β· 2020
0.60