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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PDE6G
phosphodiesterase 6G
Chromosome 17 Β· 17q25.3
NCBI Gene: 5148Ensembl: ENSG00000185527.13HGNC: HGNC:8789UniProt: P18545
30PubMed Papers
21Diseases
2Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
visual perceptionprotein bindingpositive regulation of G protein-coupled receptor signaling pathwayphotoreceptor outer segmentretinitis pigmentosacoronary artery diseasestrokePosterior column ataxia - retinitis pigmentosa
✦AI Summary

PDE6G encodes the gamma subunit of the cGMP-phosphodiesterase 6 complex, a critical effector in vertebrate photoreceptor phototransduction 1. The PDE6 complex, composed of alpha, beta, and two gamma subunits, plays a central role in rod and cone phototransduction by hydrolyzing cGMP in response to photons, thereby closing cGMP-gated ion channels and hyperpolarizing photoreceptor cells to transduce visual signals 2. PDE6G maintains intracellular cGMP levels essential for photoreceptor function and visual perception 2. Pathogenic variants in PDE6G cause autosomal recessive retinitis pigmentosa (AR-RP), accounting for 2-5% of all RP cases, with mutations in PDE6G associated with early-onset disease 32. Complex heterozygous mutations can result in severe early-onset RP presenting with high hyperopia, astigmatism, and characteristic bone spicule-type pigment deposits 4. Beyond inherited retinal disease, PDE6G has been identified as a hub gene correlated with diabetic retinopathy pathogenesis 5, and genome-wide association studies identified PDE6G-containing loci associated with strabismus risk 6. These findings establish PDE6G as a critical phototransduction protein with significant clinical relevance to multiple retinal disorders.

Sources cited
1
PDE6G is a gene encoding a phototransduction protein involved in inherited retinal disease including retinitis pigmentosa
PMID: 40013354
2
PDE6G is one of two gamma subunits in the PDE6 complex; mutations cause AR-RP by impairing cGMP hydrolysis and photoreceptor hyperpolarization; associated with early-onset RP
PMID: 40736827
3
PDE6 genes including PDE6G have higher prevalence (2-5% of RP cases) among genes causing autosomal recessive RP
PMID: 30578498
4
Complex heterozygous PDE6G mutations cause autosomal recessive RP with early-onset presentation and characteristic fundoscopic findings
PMID: 39160471
5
PDE6G is identified as a hub gene correlated with diabetic retinopathy
PMID: 37318461
6
PDE6G-containing locus (NPLOC4-TSPAN10-PDE6G-FAAP100) is associated with strabismus risk
PMID: 40849414
Disease Associationsβ“˜21
retinitis pigmentosaOpen Targets
0.73Strong
coronary artery diseaseOpen Targets
0.54Moderate
strokeOpen Targets
0.54Moderate
Posterior column ataxia - retinitis pigmentosaOpen Targets
0.40Weak
Retinal dystrophyOpen Targets
0.40Weak
cardiovascular diseaseOpen Targets
0.39Weak
eye diseaseOpen Targets
0.38Weak
hypertensionOpen Targets
0.37Weak
intermittent vascular claudicationOpen Targets
0.37Weak
Recurrent thrombophlebitisOpen Targets
0.37Weak
chronic kidney diseaseOpen Targets
0.35Weak
Hepatitis, AlcoholicOpen Targets
0.33Weak
Neonatal sepsisOpen Targets
0.32Weak
non-alcoholic steatohepatitisOpen Targets
0.31Weak
COVID-19Open Targets
0.29Weak
necrotizing enterocolitisOpen Targets
0.28Weak
osteonecrosisOpen Targets
0.28Weak
chronic renal failure syndromeOpen Targets
0.27Weak
cirrhosis of liverOpen Targets
0.26Weak
glomerulonephritisOpen Targets
0.26Weak
Retinitis pigmentosa 57UniProt
Pathogenic Variants4
NM_002602.4(PDE6G):c.97C>T (p.Arg33Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 33
NM_002602.4(PDE6G):c.69dup (p.Arg24fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 24
NM_002602.4(PDE6G):c.146+1G>TPathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2018
NM_002602.4(PDE6G):c.187+1G>TPathogenic
Retinitis pigmentosa 57|Retinitis pigmentosa
β˜†β˜†β˜†β˜†2019
View on ClinVar β†—
Drug Targets2
DIPYRIDAMOLEApproved
3',5'-cyclic phosphodiesterase inhibitor
coronary artery disease
PENTOXIFYLLINEApproved
Adenosine A2 receptor antagonist
cardiovascular disease
Related Genes
PDE6HShared pathway100%GMPRProtein interaction100%GUCY1A2Protein interaction100%GUCY1A1Protein interaction100%GUCY1B1Protein interaction100%GUCY2CProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
27%
Liver
18%
Heart
4%
Ovary
2%
Brain
0%
Gene Interaction Network
Click a node to explore
PDE6GPDE6HGMPRGUCY1A2GUCY1A1GUCY1B1GUCY2C
PROTEIN STRUCTURE
Preparing viewer…
PDB3JWR Β· 2.99 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.45LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.86 [0.53–1.45]
RankingsWhere PDE6G stands among ~20K protein-coding genes
  • #11,999of 20,598
    Most Researched30
  • #687of 1,025
    FDA-Approved Drug Targets2
  • #3,834of 5,498
    Most Pathogenic Variants4
  • #14,825of 17,882
    Most Constrained (LOEUF)1.45
Genes detectedPDE6G
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301590
1.00
2
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
PMID: 40013354
Clin Exp Ophthalmol Β· 2025
0.90
3
Retinitis Pigmentosa (Non-syndromic).
PMID: 30578498
Adv Exp Med Biol Β· 2018
0.80
4
Retinitis Pigmentosa (Non-syndromic).
PMID: 40736827
Adv Exp Med Biol Β· 2025
0.70
5
lncRNA MALAT1 promotes diabetic retinopathy by upregulating PDE6G via miR-378a-3p.
PMID: 34674599
Arch Physiol Biochem Β· 2024
0.60