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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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PDE6C
phosphodiesterase 6C
Chromosome 10 Β· 10q23.33
NCBI Gene: 5146Ensembl: ENSG00000095464.10HGNC: HGNC:8787UniProt: P51160
37PubMed Papers
22Diseases
2Drugs
104Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
visual perceptionnegative regulation of cAMP/PKA signal transduction3',5'-cyclic-GMP phosphodiesterase activity3',5'-cyclic-AMP phosphodiesterase activityachromatopsiaCone rod dystrophycoronary artery diseasestroke
✦AI Summary

PDE6C (phosphodiesterase 6C) is a cone-specific cGMP phosphodiesterase that plays an essential role in cone phototransduction by rapidly decreasing intracellular cGMP levels in response to light stimulation 1. This enzyme is part of the cone phototransduction cascade and works in coordination with other cGMP metabolism regulators; its stability and function are interdependent with other phototransduction proteins like guanylate cyclase 2. Pathogenic variants in PDE6C cause achromatopsia and cone dystrophy, disorders affecting color vision and cone photoreceptor function 34. PDE6C mutations account for a portion of achromatopsia cases, though CNGA3 and CNGB3 variants are more prevalent 1. PDE6C-related retinopathy presents as a severe cone dysfunction syndrome characterized by early-onset nystagmus, poor visual acuity, complete color vision loss, photophobia, and progressive maculopathy with outer retinal atrophy 56. Some patients develop cone-rod dystrophy with additional scotopic dysfunction and visual field constriction 6. High myopia frequently accompanies PDE6C-related disease 5. Clinically, affected individuals typically present at birth or early infancy with poor vision and color blindness 1. Currently, no FDA-approved treatments exist, though gene therapy approaches show preclinical promise with clinical trials underway 1.

Sources cited
1
PDE6C mutations cause achromatopsia; early presentation with poor visual acuity, nystagmus, photophobia, and color vision loss; gene therapy trials ongoing
PMID: 39273686
2
PDE6C is one of several genes associated with cone dysfunction syndromes and achromatopsia
PMID: 38278208
3
PDE6C encodes a phototransduction protein; pathogenic variants cause significant vision impairment in inherited retinal disease
PMID: 40013354
4
PDE6C achromatopsia presents with early-onset nystagmus, decreased visual acuity, light sensitivity, severe color vision loss, high myopia, and progressive outer retinal atrophy
PMID: 31826238
5
PDE6C variants cause cone and cone-rod dystrophy with early-onset nystagmus, poor color discrimination, visual field constriction, and night blindness
PMID: 33001157
6
Pde6c stability and function are interdependent with other cGMP metabolism regulators including Aipl1 and guanylate cyclase
PMID: 28378769
Disease Associationsβ“˜22
achromatopsiaOpen Targets
0.78Strong
Cone rod dystrophyOpen Targets
0.72Strong
coronary artery diseaseOpen Targets
0.54Moderate
strokeOpen Targets
0.54Moderate
Retinal dystrophyOpen Targets
0.54Moderate
cone dystrophyOpen Targets
0.46Moderate
autosomal recessive cone rod dystrophyOpen Targets
0.40Weak
cardiovascular diseaseOpen Targets
0.39Weak
Progressive cone dystrophyOpen Targets
0.37Weak
eye diseaseOpen Targets
0.37Weak
hypertensionOpen Targets
0.37Weak
intermittent vascular claudicationOpen Targets
0.37Weak
Recurrent thrombophlebitisOpen Targets
0.37Weak
chronic kidney diseaseOpen Targets
0.35Weak
isolated macular dystrophyOpen Targets
0.34Weak
Hepatitis, AlcoholicOpen Targets
0.33Weak
Neonatal sepsisOpen Targets
0.32Weak
non-alcoholic steatohepatitisOpen Targets
0.31Weak
COVID-19Open Targets
0.29Weak
osteonecrosisOpen Targets
0.28Weak
Achromatopsia 5UniProt
Cone dystrophy 4UniProt
Pathogenic Variants104
NM_006204.4(PDE6C):c.801_804del (p.Val268fs)Pathogenic
not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2026β†’ Residue 268
NM_006204.4(PDE6C):c.775C>T (p.Arg259Ter)Pathogenic
Achromatopsia|Cone dystrophy 4|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 259
NM_006204.4(PDE6C):c.1579C>T (p.Arg527Ter)Pathogenic
Achromatopsia|not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2026β†’ Residue 527
NM_006204.4(PDE6C):c.939+5G>APathogenic
not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2025
NM_006204.4(PDE6C):c.85C>T (p.Arg29Trp)Pathogenic
Cone dystrophy 4|Achromatopsia 5|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 29
NM_006204.4(PDE6C):c.939+2T>GPathogenic
not provided|PDE6C-related disorder
β˜…β˜…β˜†β˜†2025
NM_006204.4(PDE6C):c.1004+1G>APathogenic
not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2025
NM_006204.4(PDE6C):c.2053del (p.Gln685fs)Pathogenic
Cone dystrophy 4
β˜…β˜…β˜†β˜†2025β†’ Residue 685
NM_006204.4(PDE6C):c.1669C>T (p.Arg557Ter)Pathogenic
not provided|PDE6C-related disorder|Cone dystrophy 4|Retinal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 557
NM_006204.4(PDE6C):c.2192G>A (p.Trp731Ter)Pathogenic
Cone dystrophy 4|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 731
NM_006204.4(PDE6C):c.2367+1_2367+5delPathogenic
Achromatopsia 5|not provided|Cone dystrophy 4|Retinal dystrophy
β˜…β˜…β˜†β˜†2024
NM_006204.4(PDE6C):c.2283+1G>TPathogenic
Cone dystrophy 4|not provided
β˜…β˜…β˜†β˜†2024
NM_006204.4(PDE6C):c.2304_2305del (p.Arg769_Asp770insTer)Pathogenic
Retinal dystrophy|not provided|PDE6C-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 769
NM_006204.4(PDE6C):c.1336G>T (p.Glu446Ter)Pathogenic
Cone dystrophy 4
β˜…β˜…β˜†β˜†2023β†’ Residue 446
NM_006204.4(PDE6C):c.481-1G>ALikely pathogenic
Retinal dystrophy|not provided
β˜…β˜…β˜†β˜†2022
NM_006204.4(PDE6C):c.1958T>C (p.Leu653Pro)Likely pathogenic
Cone dystrophy 4|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 653
NM_006204.4(PDE6C):c.2126_2129del (p.Thr709fs)Pathogenic
not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2022β†’ Residue 709
NM_006204.4(PDE6C):c.712C>T (p.Arg238Ter)Pathogenic
not provided|Cone dystrophy 4
β˜…β˜…β˜†β˜†2022β†’ Residue 238
NM_006204.4(PDE6C):c.1269+1G>APathogenic
Achromatopsia|not provided
β˜…β˜…β˜†β˜†2019
NM_006204.4(PDE6C):c.1921_1922del (p.Leu641fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 641
View on ClinVar β†—
Drug Targets2
DIPYRIDAMOLEApproved
3',5'-cyclic phosphodiesterase inhibitor
coronary artery disease
PENTOXIFYLLINEApproved
Adenosine A2 receptor antagonist
cardiovascular disease
Related Genes
APRTProtein interaction95%ADCY4Protein interaction95%GMPSProtein interaction93%ADCY1Protein interaction92%ADCY6Protein interaction91%ITPAProtein interaction90%
Tissue Expression6 tissues
Ovary
100%
Liver
79%
Bone Marrow
65%
Lung
64%
Brain
29%
Heart
26%
Gene Interaction Network
Click a node to explore
PDE6CAPRTADCY4GMPSADCY1ADCY6ITPA
PROTEIN STRUCTURE
Preparing viewer…
PDB5E8F Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.98LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.62–0.98]
RankingsWhere PDE6C stands among ~20K protein-coding genes
  • #10,665of 20,598
    Most Researched37
  • #678of 1,025
    FDA-Approved Drug Targets2
  • #747of 5,498
    Most Pathogenic Variants104 Β· top quartile
  • #9,292of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedPDE6C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Gene Therapy for Achromatopsia.
PMID: 39273686
Int J Mol Sci Β· 2024
1.00
2
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
0.90
3
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
PMID: 40013354
Clin Exp Ophthalmol Β· 2025
0.80
4
An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas.
PMID: 35644251
Dev Biol Β· 2022
0.70
5
PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.
PMID: 33001157
Invest Ophthalmol Vis Sci Β· 2020
0.60