PDE4B Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the PDE4B gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PDE4B |
|---|---|
| Full Name | Phosphodiesterase 4B |
| Gene Type | protein-coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 5142 ncbi.nlm.nih.gov/gene/5142 |
| Ensembl ID | ENSG00000184588 |
| UniProt ID | Q07343 |
| OMIM ID | 600127 |
| HGNC ID | 8781 |
| Aliases | DPDE4, PDEIVB |
Description
PDE4B encodes a member of the cyclic nucleotide phosphodiesterase family, specifically the cAMP-specific 3',5'-cyclic phosphodiesterase 4B. This enzyme plays a critical role in regulating intracellular cAMP levels, thereby influencing various cellular processes including inflammation, neuronal signaling, and cell proliferation. The gene is located on chromosome 1p31.3 and is expressed in multiple tissues, with highest levels in the brain and immune cells. PDE4B has been implicated in several diseases, including psychiatric disorders, inflammatory conditions, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Genetic variants and altered expression of PDE4B may disrupt cAMP signaling, affecting neuronal function and contributing to schizophrenia susceptibility. | Association studies and GWAS have linked PDE4B variants to schizophrenia risk (e.g., PMID: 21376230). |
| Chronic Obstructive Pulmonary Disease (COPD) | PDE4B is a key enzyme in inflammatory cells; its inhibition reduces inflammation, making it a therapeutic target for COPD. | Clinical trials of PDE4 inhibitors (e.g., roflumilast) show efficacy in COPD, and PDE4B is a major target (PMID: 20592963). |
| Major Depressive Disorder | PDE4B modulates cAMP signaling in the brain, and its inhibition has antidepressant effects in animal models. | Preclinical studies show PDE4 inhibitors produce antidepressant-like effects; PDE4B knockout mice exhibit reduced depressive behavior (PMID: 19197004). |
| Cancer | PDE4B is overexpressed in some cancers, promoting tumor cell proliferation and survival via cAMP regulation. | Expression data from COSMIC and literature indicate PDE4B upregulation in certain tumors (e.g., PMID: 24336713). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in cerebral cortex, hippocampus, and cerebellum. |
| Lung | Moderate | Moderate expression in lung tissue. |
| Spleen | Moderate | Moderate expression in spleen. |
| Blood | Moderate | Expression in leukocytes. |
| Liver | Low | Low expression in liver. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Moderate | Embryonic kidney cells; used for functional studies. |
| HeLa | Low | Cervical cancer cell line. |
| A549 | Moderate | Lung carcinoma cell line; relevant for COPD studies. |
| Jurkat | High | T-cell leukemia line; high expression in immune cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1040716 | SNP (intronic) | Allele frequency varies by population (e.g., ~0.3 in Europeans) | Associated with schizophrenia risk in some studies. |
| c.1234C>T (p.Arg412Cys) | Missense | Rare (MAF <0.01) | Potential functional impact on enzyme activity; not well characterized. |
| c.1567G>A (p.Val523Met) | Missense | Rare | Reported in COSMIC; possible role in cancer. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PDE4B are rare but may lead to increased cAMP levels, potentially affecting immune and neuronal signaling. No specific pathogenic variants are well-documented in ClinVar.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported; however, overexpression of PDE4B in certain cancers may mimic a gain-of-function effect, reducing cAMP and promoting proliferation.
Dominant Negative (DN)
No dominant-negative mutations have been described for PDE4B.
View complete mutation data：
Gene Ontology (GO)
| • 3' | • 5'-cyclic-AMP phosphodiesterase activity |
| • cAMP binding | • metal ion binding |
| • signal transduction | • inflammatory response |
| • negative regulation of cAMP-mediated signaling |
Pathways
• cAMP signaling pathway
• G protein-coupled receptor signaling pathway
• Inflammatory mediator regulation of TRP channels
• Dopamine receptor signaling pathway
Protein Summary
The PDE4B protein is a 736-amino acid enzyme that specifically hydrolyzes cAMP to AMP, thereby regulating intracellular cAMP levels. It contains an N-terminal regulatory domain, a catalytic domain, and a C-terminal region. PDE4B is expressed in various tissues, with high levels in the brain and immune cells. It plays a role in inflammatory responses, neuronal plasticity, and cell proliferation. Alternative splicing generates multiple isoforms with distinct regulatory properties. PDE4B is a target for anti-inflammatory drugs like roflumilast.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE4B Knockout HEK293 Cell Line | EDJ-KQ1829 | Human | 5142 | Details Get a Quote |
| PDE4B Knockout A-549 Cell Line | EDJ-KQ20367 | Human | 5142 | Details Get a Quote |
| PDE4B Knockout HCT 116 Cell Line | EDJ-KQ21684 | Human | 5142 | Details Get a Quote |
| PDE4B Knockout HeLa Cell Line | EDJ-KQ21685 | Human | 5142 | Details Get a Quote |
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