PDE4D: Phosphodiesterase 4D – Key Regulator of cAMP Signaling
Comprehensive gene card for PDE4D, including genomic data, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | PDE4D |
|---|---|
| Full Name | Phosphodiesterase 4D |
| Gene Type | protein-coding |
| Chromosomal Location | 5q11.2-q12.1 |
| NCBI Gene ID | 5144 ncbi.nlm.nih.gov/gene/5144 |
| Ensembl ID | ENSG00000113448 |
| UniProt ID | Q08499 |
| OMIM ID | 600129 |
| HGNC ID | 8783 |
| Aliases | DPDE3, PDE4DN, PDE4D5, PDE4D6, PDE4D7, PDE4D8, PDE4D9, PDE4D10 |
Description
PDE4D encodes a member of the type IV cyclic nucleotide phosphodiesterase family, which specifically hydrolyzes cyclic AMP (cAMP) to AMP. This enzyme plays a critical role in regulating intracellular cAMP levels and is involved in signal transduction pathways controlling inflammation, cognition, and vascular smooth muscle contraction. Alternative splicing generates multiple isoforms with distinct N-termini and regulatory properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acrodysostosis 2 (ACRDYS2) | Loss-of-function mutations in PDE4D impair cAMP degradation, leading to skeletal abnormalities and intellectual disability. | OMIM #614613 |
| Stroke (ischemic) | Genetic variants in PDE4D have been associated with increased risk of ischemic stroke, possibly through altered cAMP signaling in vascular endothelium. | PMID: 12511656, ClinVar |
| Major depressive disorder | PDE4D is a target for antidepressant drugs; altered expression may contribute to mood regulation. | PMID: 23042169 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Skeletal Muscle | 3.8 | Low |
| Kidney | 7.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression in embryonic kidney cells |
| SH-SY5Y | 8.7 | Neuroblastoma cell line; moderate expression |
| A549 | 5.4 | Lung carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130G>A (p.Glu44Lys) | Missense | <0.01% | Reduced catalytic activity; associated with acrodysostosis |
| c.688C>T (p.Arg230Cys) | Missense | <0.01% | Impaired cAMP hydrolysis; linked to ACRDYS2 |
| rs12153798 (intronic) | SNP | 0.15 (allele frequency) | Associated with increased stroke risk in some populations |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Glu44Lys, p.Arg230Cys) reduce PDE4D enzymatic activity, leading to elevated cAMP levels and acrodysostosis.
Gain of Function (GOF)
Not well documented; some variants may increase activity but are not clinically validated.
Dominant Negative (DN)
Not reported for PDE4D.
View complete mutation data：
Gene Ontology (GO)
| • 3' | • 5'-cyclic-AMP phosphodiesterase activity |
| • cAMP binding | • signal transduction |
| • negative regulation of cAMP-mediated signaling | • inflammatory response |
| • nervous system development |
Pathways
• cAMP signaling pathway (Reactome: R-HSA-418555)
• G alpha (s) signalling events (Reactome: R-HSA-388396)
• PDE4D in regulation of smooth muscle contraction (KEGG: hsa04024)
Protein Summary
PDE4D is a 736-amino acid protein (isoform 1) that belongs to the PDE4 family. It contains a catalytic domain and two upstream conserved regions (UCR1 and UCR2) that regulate dimerization and activity. The enzyme is inhibited by rolipram and other selective PDE4 inhibitors, which are used therapeutically for inflammatory and psychiatric disorders. PDE4D is expressed in multiple tissues, with highest levels in brain and heart.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE4D Knockout HEK293 Cell Line | EDJ-KQ1831 | Human | 5144 | Details Get a Quote |
| PDE4D Knockout A-549 Cell Line | EDJ-KQ21686 | Human | 5144 | Details Get a Quote |
| PDE4D Knockout HeLa Cell Line | EDJ-KQ21687 | Human | 5144 | Details Get a Quote |
| PDE4D Knockout HCT 116 Cell Line | EDJ-KQ71061 | Human | 5144 | Details Get a Quote |
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