PDE6D (Phosphodiesterase 6D): A Prenyl-Binding Protein with Emerging Roles in Retinal and Cancer Biology
Comprehensive gene card, expression, mutations, and clinical relevance of PDE6D, a key regulator of prenylated protein trafficking and Hedgehog signaling.
Gene Information Card
| Symbol | PDE6D |
|---|---|
| Full Name | Phosphodiesterase 6D, cGMP-specific, rod, delta |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 5147 ncbi.nlm.nih.gov/gene/5147 |
| Ensembl ID | ENSG00000163110 |
| UniProt ID | O43924 |
| OMIM ID | 602676 |
| HGNC ID | 8788 |
| Aliases | JBTS22; PDED; PDE6D; RP55 |
Description
PDE6D encodes the delta subunit of rod cGMP phosphodiesterase, but its primary function is as a prenyl-binding protein that solubilizes and traffics prenylated small GTPases (e.g., Rheb, Rab13, and the Hedgehog pathway regulator GNAI1). It is essential for ciliary transport and Hedgehog signaling, and mutations cause Joubert syndrome and retinitis pigmentosa. PDE6D is also implicated in cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Joubert syndrome 22 (JBTS22) | Biallelic loss-of-function mutations impair ciliary trafficking, leading to cerebellar and retinal defects. | OMIM #602676; PMID: 28130473 |
| Retinitis pigmentosa 55 (RP55) | Mutations disrupt prenyl-binding, causing photoreceptor degeneration. | OMIM #602676; PMID: 28130473 |
| Cancer (multiple types) | Overexpression or altered localization promotes oncogenic signaling (e.g., Hedgehog, KRAS) in various tumors. | COSMIC; PMID: 28130473 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 32.2 | High |
| Brain (cerebellum) | 25.1 | High |
| Retina | 20.5 | High |
| Lung | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer; moderate expression |
| A549 | 12.8 | Lung cancer; moderate |
| MCF7 | 10.1 | Breast cancer; moderate |
| HepG2 | 8.5 | Liver cancer; low-moderate |
| K562 | 6.3 | Leukemia; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Ter) | Nonsense | Rare (found in JBTS22) | Loss of function; truncates protein, abolishing prenyl-binding |
| c.274G>A (p.Gly92Arg) | Missense | Rare (found in RP55) | Loss of function; disrupts binding to prenylated cargo |
| c.337C>T (p.Arg113Trp) | Missense | Rare (found in JBTS22) | Loss of function; impairs ciliary localization |
| c.412A>G (p.Thr138Ala) | Missense | Somatic (COSMIC) | Unknown; may affect protein stability |
Mutation functional classification
Loss of Function (LOF)
Most PDE6D mutations are loss-of-function, leading to impaired prenyl-binding and defective ciliary trafficking, causing retinal and cerebellar phenotypes.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression in cancer may act as a dominant effect.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by sequestering cargo, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• cGMP-PDE signaling (Reactome: R-HSA-418457)
• Cargo trafficking to the primary cilium (Reactome: R-HSA-5620912)
Protein Summary
PDE6D is a small (17 kDa) protein that binds to prenylated proteins via its hydrophobic pocket, facilitating their membrane extraction and transport. It is critical for the proper localization of ciliary proteins and Hedgehog signaling. Mutations cause ciliopathies, and its dysregulation is linked to cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE6D Knockout HEK293 Cell Line | EDJ-KQ50506 | Human | 5147 | Details Get a Quote |
| PDE6D Knockout HeLa Cell Line | EDJ-KQ54103 | Human | 5147 | Details Get a Quote |
| PDE6D Knockout A-549 Cell Line | EDJ-KQ62592 | Human | 5147 | Details Get a Quote |
| PDE6D Knockout HCT 116 Cell Line | EDJ-KQ71064 | Human | 5147 | Details Get a Quote |
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