PDE2A: Phosphodiesterase 2A – cGMP and cAMP Signaling Regulator
A dual-substrate cyclic nucleotide phosphodiesterase implicated in neurological, cardiovascular, and cancer biology
Gene Information Card
| Symbol | PDE2A |
|---|---|
| Full Name | Phosphodiesterase 2A |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 5138 ncbi.nlm.nih.gov/gene/5138 |
| Ensembl ID | ENSG00000137767 |
| UniProt ID | O00408 |
| OMIM ID | 602658 |
| HGNC ID | 8777 |
| Aliases | PDE2, cGMP-stimulated phosphodiesterase, PDE2A1, PDE2A2, PDE2A3 |
Description
PDE2A encodes a cyclic nucleotide phosphodiesterase that hydrolyzes both cAMP and cGMP, with a higher affinity for cGMP. It is allosterically activated by cGMP binding to its GAF-B domain. PDE2A plays critical roles in cellular signaling, particularly in the brain, heart, and adrenal cortex, and is implicated in cognitive function, cardiac contractility, and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Altered PDE2A expression affects cAMP/cGMP signaling, contributing to cognitive decline and amyloid pathology. | ClinVar; PMID: 25664854 |
| Schizophrenia | PDE2A variants and expression changes linked to disrupted cyclic nucleotide signaling in prefrontal cortex. | ClinVar; PMID: 23894747 |
| Cardiac hypertrophy | PDE2A upregulation reduces cGMP levels, promoting pathological hypertrophy. | PMID: 25664854 |
| Colorectal cancer | PDE2A overexpression correlates with poor prognosis; modulates cAMP signaling to promote proliferation. | COSMIC; PMID: 25664854 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Heart (left ventricle) | 8.3 | Medium |
| Adrenal gland | 15.2 | High |
| Lung | 4.1 | Low |
| Liver | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.8 | High expression |
| HEK293 (embryonic kidney) | 6.2 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 1.5 | Low expression |
| A549 (lung carcinoma) | 3.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.001% (gnomAD) | Reduced catalytic activity; associated with neuropsychiatric disorders |
| c.1582G>A (p.Glu528Lys) | Missense | 0.0005% (gnomAD) | Altered cGMP binding affinity; potential gain-of-function |
| c.1972_1973insA (p.Thr658Asnfs*2) | Frameshift | <0.0001% (COSMIC) | Loss of function; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the catalytic domain reduce or abolish cAMP/cGMP hydrolysis.
Gain of Function (GOF)
Missense mutations that enhance catalytic activity or cGMP sensitivity may increase cyclic nucleotide turnover.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with dimerization or GAF domain function.
View complete mutation data：
Gene Ontology (GO)
| • 3' | • 5'-cyclic-nucleotide phosphodiesterase activity |
| • cGMP binding | • cAMP binding |
| • cGMP-stimulated cyclic-nucleotide phosphodiesterase activity | • signal transduction |
| • regulation of cardiac muscle contraction | • learning and memory |
Pathways
• cGMP-PKG signaling pathway
• cAMP-PKA signaling pathway
• Alzheimer disease – presenilin pathway
• Cardiac hypertrophy signaling
Protein Summary
PDE2A is a 941-amino acid protein containing two N-terminal GAF domains (GAF-A and GAF-B) and a C-terminal catalytic domain. GAF-B binds cGMP with high affinity, allosterically activating the enzyme. PDE2A exists as a homodimer and is localized to the cytosol and membrane fractions. It is highly expressed in brain, heart, and adrenal cortex, where it regulates cyclic nucleotide levels and downstream signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE2A Knockout HEK293 Cell Line | EDJ-KQ1851 | Human | 5138 | Details Get a Quote |
| PDE2A Knockout A-549 Cell Line | EDJ-KQ21715 | Human | 5138 | Details Get a Quote |
| PDE2A Knockout HCT 116 Cell Line | EDJ-KQ21716 | Human | 5138 | Details Get a Quote |
| PDE2A Knockout HeLa Cell Line | EDJ-KQ21717 | Human | 5138 | Details Get a Quote |
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