PDE6H: Phosphodiesterase 6H, cGMP-Specific, Cone, Gamma Subunit
Key regulator of phototransduction in cone photoreceptors; mutations linked to retinal dystrophies
Gene Information Card
| Symbol | PDE6H |
|---|---|
| Full Name | Phosphodiesterase 6H, cGMP-Specific, Cone, Gamma Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.1 |
| NCBI Gene ID | 5149 ncbi.nlm.nih.gov/gene/5149 |
| Ensembl ID | ENSG00000111247 |
| UniProt ID | Q13956 |
| OMIM ID | 601190 |
| HGNC ID | 8791 |
| Aliases | PDE6G, GMP-PDE6, PDE6gamma |
Description
PDE6H encodes the gamma subunit of the cone-specific cGMP phosphodiesterase (PDE6) holoenzyme, a key effector enzyme in the phototransduction cascade of cone photoreceptors. The gamma subunit inhibits the catalytic alpha and beta subunits in the dark; upon light activation, transducin relieves this inhibition, allowing cGMP hydrolysis and closure of cGMP-gated ion channels. Mutations in PDE6H are associated with autosomal recessive achromatopsia and cone dystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Achromatopsia 5 (ACHM5) | Loss-of-function mutations in PDE6H impair cone PDE6 activity, disrupting phototransduction and causing severe color vision deficiency, nystagmus, and photophobia. | OMIM #614600; ClinVar |
| Cone dystrophy | Defects in PDE6H lead to progressive degeneration of cone photoreceptors, resulting in reduced visual acuity and color vision loss. | OMIM; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 27.8 | High |
| Testis | 0.6 | Low |
| Brain | 0.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 | 0.0 | Not expressed |
| Y79 | 15.2 | Retinoblastoma cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1Thr) | Missense | Rare | Loss of start codon; no functional protein |
| c.121C>T (p.Arg41*) | Nonsense | Rare | Premature stop; truncated protein |
| c.217G>A (p.Gly73Arg) | Missense | Rare | Impaired gamma subunit binding to catalytic subunits |
Mutation functional classification
Loss of Function (LOF)
Most reported PDE6H mutations are loss-of-function, leading to reduced or absent PDE6 activity in cones, causing achromatopsia.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • 3' | • 5'-cyclic-GMP phosphodiesterase activity |
| • cGMP binding | • phototransduction |
| • visual perception | • response to light stimulus |
| • signal transduction |
Pathways
• Phototransduction cascade (KEGG: hsa04744)
• cGMP-PKG signaling pathway
Protein Summary
The PDE6H protein (gamma subunit of cone PDE6) is a small inhibitory subunit (approx. 10 kDa) that regulates the catalytic activity of the PDE6 holoenzyme. In the dark, it binds to and inhibits the alpha and beta catalytic subunits. Light-activated transducin interacts with the gamma subunit, relieving inhibition and allowing rapid cGMP hydrolysis. This protein is essential for proper cone phototransduction and color vision.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE6H Knockout HEK293 Cell Line | EDJ-KQ5428 | Human | 5149 | Details Get a Quote |
| PDE6H Knockout HeLa Cell Line | EDJ-KQ54105 | Human | 5149 | Details Get a Quote |
| PDE6H Knockout A-549 Cell Line | EDJ-KQ62593 | Human | 5149 | Details Get a Quote |
| PDE6H Knockout HCT 116 Cell Line | EDJ-KQ71066 | Human | 5149 | Details Get a Quote |
