PDE4A: Phosphodiesterase 4A, cAMP-Specific
A key regulator of cAMP signaling in inflammation, cognition, and cancer
Gene Information Card
| Symbol | PDE4A |
|---|---|
| Full Name | Phosphodiesterase 4A, cAMP-Specific |
| Gene Type | Protein-coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 5141 ncbi.nlm.nih.gov/gene/5141 |
| Ensembl ID | ENSG00000165949 |
| UniProt ID | P27815 |
| OMIM ID | 600126 |
| HGNC ID | 8780 |
| Aliases | DPDE2, PDE4, PDE4A1, PDE4A4, PDE4A5, PDE4A6, PDE4A7, PDE4A8, PDE4A10, PDE4A11 |
Description
PDE4A encodes a member of the type IV cyclic nucleotide phosphodiesterase family that specifically hydrolyzes cyclic AMP (cAMP) to AMP, thereby regulating intracellular cAMP levels. This enzyme plays a critical role in signal transduction pathways involved in inflammation, cognition, and cell proliferation. Alternative splicing generates multiple isoforms with distinct N-terminal domains that influence subcellular localization and regulatory properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Major depressive disorder | Altered cAMP signaling in brain regions; PDE4A overexpression linked to reduced cAMP response | PMID: 20663977 |
| Schizophrenia | Genetic association studies implicate PDE4A variants in susceptibility; cAMP dysregulation in prefrontal cortex | PMID: 17903296 |
| Asthma | PDE4A expression in airway smooth muscle and inflammatory cells; inhibition reduces bronchoconstriction and inflammation | PMID: 15994372 |
| Chronic obstructive pulmonary disease (COPD) | Increased PDE4A activity in lung tissue; contributes to inflammation and airway remodeling | PMID: 21532038 |
| Cancer (various) | Dysregulated cAMP signaling promotes proliferation; PDE4A overexpression in melanoma, breast, and lung cancers | PMID: 23543789 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Heart | 6.1 | Low |
| Spleen | 15.2 | Medium |
| Testis | 22.8 | High |
| Adrenal gland | 18.4 | Medium |
| Thyroid | 9.7 | Low |
| Prostate | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | Embryonic kidney; high expression |
| A549 | 9.8 | Lung carcinoma; moderate expression |
| MCF7 | 6.2 | Breast cancer; low expression |
| SH-SY5Y | 18.1 | Neuroblastoma; high expression |
| Jurkat | 11.5 | T-cell leukemia; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Reduced catalytic activity; associated with altered cAMP response |
| c.457G>A (p.Gly153Ser) | Missense | <0.01% | Decreased enzyme stability; potential loss-of-function |
| c.1234A>G (p.Thr412Ala) | Missense | 0.02% | No significant effect on activity; benign polymorphism |
| c.1789C>T (p.Arg597Cys) | Missense | <0.01% | Impaired interaction with regulatory proteins |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.Arg34Trp and p.Gly153Ser reduce catalytic activity or protein stability, leading to decreased cAMP hydrolysis and altered signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PDE4A.
Dominant Negative (DN)
No dominant-negative mutations described for PDE4A.
View complete mutation data：
Gene Ontology (GO)
Pathways
• cAMP signaling pathway (Reactome: R-HSA-163615)
• G alpha (s) signalling events (Reactome: R-HSA-388396)
• PKA-mediated phosphorylation of CREB (Reactome: R-HSA-111931)
• Regulation of insulin secretion (KEGG: hsa04911)
Protein Summary
PDE4A is a 686-amino acid protein (isoform 1) that belongs to the PDE4 family of cAMP-specific phosphodiesterases. It contains a catalytic domain and two upstream conserved regions (UCR1 and UCR2) that regulate dimerization and activity. The enzyme is expressed in multiple tissues, with highest levels in brain and testis. PDE4A is involved in diverse physiological processes including inflammation, cognition, and cell growth. Its activity is modulated by phosphorylation and interaction with scaffold proteins such as AKAPs. Dysregulation of PDE4A is implicated in psychiatric disorders, respiratory diseases, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE4A Knockout HEK293 Cell Line | EDJ-KQ1828 | Human | 5141 | Details Get a Quote |
| PDE4A Knockout A-549 Cell Line | EDJ-KQ21680 | Human | 5141 | Details Get a Quote |
| PDE4A Knockout HCT 116 Cell Line | EDJ-KQ21681 | Human | 5141 | Details Get a Quote |
| PDE4A Knockout HeLa Cell Line | EDJ-KQ21682 | Human | 5141 | Details Get a Quote |
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