PDE6G: The Gamma Subunit of Retinal cGMP Phosphodiesterase
A critical component of the phototransduction cascade; mutations cause retinitis pigmentosa and congenital stationary night blindness.
Gene Information Card
| Symbol | PDE6G |
|---|---|
| Full Name | Phosphodiesterase 6G, cGMP-specific, rod, gamma |
| Gene Type | protein-coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 5148 ncbi.nlm.nih.gov/gene/5148 |
| Ensembl ID | ENSG00000185527 |
| UniProt ID | P18545 |
| OMIM ID | 180073 |
| HGNC ID | 8789 |
| Aliases | GMP-PDE gamma, PDE6 gamma, RP57, CSNB3 |
Description
PDE6G encodes the gamma subunit of the rod cGMP phosphodiesterase (PDE6) holoenzyme, a key effector enzyme in the phototransduction cascade. The gamma subunit acts as an inhibitory regulator of the catalytic alpha and beta subunits. In the dark, PDE6G binds to and inhibits PDE6A/PDE6B; upon light activation, transducin releases this inhibition, allowing cGMP hydrolysis and closure of ion channels. Mutations in PDE6G disrupt this regulation, leading to retinal degeneration and vision disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis pigmentosa 57 (RP57) | Loss-of-function mutations impair PDE6 inhibition, causing constitutive cGMP hydrolysis or misregulation, leading to rod photoreceptor death. | ClinVar, OMIM |
| Congenital stationary night blindness type 3 (CSNB3) | Specific missense variants alter the inhibitory interaction with PDE6 catalytic subunits, reducing light sensitivity without progressive degeneration. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | High (nTPM not available for retina in GTEx; RNA-seq data from specialized studies show high expression) | High |
| Testis | 0.2 | Low |
| Brain | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 0.0 | Not expressed |
| Y79 (retinoblastoma) | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1Thr) | Missense (start codon loss) | Rare | Loss of function; associated with RP57 |
| c.205C>T (p.Arg69Trp) | Missense | Rare | Dominant negative; associated with CSNB3 |
| c.1A>G (p.Met1Val) | Missense (start codon loss) | Rare | Loss of function; associated with RP57 |
Mutation functional classification
Loss of Function (LOF)
Start codon mutations (e.g., p.Met1Thr, p.Met1Val) abolish protein translation, leading to haploinsufficiency and retinitis pigmentosa.
Gain of Function (GOF)
Not reported for PDE6G.
Dominant Negative (DN)
p.Arg69Trp alters the inhibitory domain, causing constitutive activation of PDE6 catalytic subunits and congenital stationary night blindness.
View complete mutation data：
Gene Ontology (GO)
| • 3 (GO:0004114) | • zinc ion binding (GO:0008270) |
| • visual perception (GO:0007601) | • detection of visible light (GO:0009584) |
| • photoreceptor outer segment (GO:0001750) | • plasma membrane (GO:0005886) |
Pathways
• Phototransduction cascade (Reactome: R-HSA-2514856)
• cGMP-PKG signaling pathway (KEGG: hsa04022)
Protein Summary
The PDE6G protein (87 amino acids, ~9.7 kDa) is a small, soluble inhibitory subunit of the rod cGMP phosphodiesterase. It contains a polycationic region that binds to the catalytic subunits, blocking their active sites in the dark. Upon light activation, the alpha subunit of transducin (GNAT1) interacts with PDE6G, relieving inhibition and allowing rapid cGMP hydrolysis. This protein is essential for the fast kinetics of phototransduction and visual adaptation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE6G Knockout HEK293 Cell Line | EDJ-KQ5427 | Human | 5148 | Details Get a Quote |
| PDE6G Knockout A-549 Cell Line | EDJ-KQ28598 | Human | 5148 | Details Get a Quote |
| PDE6G Knockout HeLa Cell Line | EDJ-KQ54104 | Human | 5148 | Details Get a Quote |
| PDE6G Knockout HCT 116 Cell Line | EDJ-KQ71065 | Human | 5148 | Details Get a Quote |
