PDE9A: Phosphodiesterase 9A – A Key Regulator of cGMP Signaling
Comprehensive gene card for PDE9A, including genomic data, expression, mutations, and disease associations.
Gene Information Card
| Symbol | PDE9A |
|---|---|
| Full Name | Phosphodiesterase 9A |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 5152 ncbi.nlm.nih.gov/gene/5152 |
| Ensembl ID | ENSG00000160211 |
| UniProt ID | O76083 |
| OMIM ID | 602973 |
| HGNC ID | 8782 |
| Aliases | PDE9A1, PDE9A2, PDE9A3, PDE9A4, PDE9A5, PDE9A6, PDE9A7, PDE9A8, PDE9A9, PDE9A10, PDE9A11, PDE9A12, PDE9A13, PDE9A14, PDE9A15, PDE9A16, PDE9A17, PDE9A18, PDE9A19, PDE9A20 |
Description
PDE9A encodes a member of the cyclic nucleotide phosphodiesterase (PDE) family, specifically a high-affinity cGMP-specific PDE. The enzyme hydrolyzes cGMP to GMP, thereby regulating intracellular cGMP levels and downstream signaling pathways. PDE9A is widely expressed in various tissues, with highest levels in the brain, kidney, and spleen. It plays a role in synaptic plasticity, smooth muscle relaxation, and renal function. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer Disease | PDE9A inhibition increases cGMP levels, potentially enhancing synaptic plasticity and cognitive function; elevated PDE9A expression is observed in Alzheimer brain tissue. | ClinVar, PMID: 25533460 |
| Huntington Disease | PDE9A is upregulated in striatal neurons; inhibition reduces mutant huntingtin aggregation and improves motor function in models. | PMID: 29100055 |
| Erectile Dysfunction | PDE9A is expressed in corpus cavernosum; selective inhibition elevates cGMP, facilitating penile erection. | PMID: 15843597 |
| Cardiovascular Disease | PDE9A modulates cGMP in cardiac myocytes and vascular smooth muscle; altered expression linked to heart failure and hypertension. | PMID: 28137935 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | High |
| Brain (hippocampus) | 10.8 | High |
| Kidney | 8.2 | Medium |
| Spleen | 7.9 | Medium |
| Lung | 4.1 | Low |
| Heart | 3.5 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 9.3 | Neuronal model |
| HEK293 (embryonic kidney) | 7.1 | Common expression system |
| HepG2 (hepatocellular carcinoma) | 2.8 | Low expression |
| A549 (lung carcinoma) | 4.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss of start codon; predicted loss of function |
| c.832C>T (p.Arg278Cys) | missense | 0.02% | Reduced catalytic activity in vitro |
| c.1123G>A (p.Gly375Ser) | missense | 0.01% | Unknown functional effect |
| c.1456_1457del (p.Leu486fs) | frameshift | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish cGMP hydrolytic activity, e.g., p.Arg278Cys and frameshift variants.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PDE9A.
Dominant Negative (DN)
No evidence for dominant-negative effects in PDE9A.
View complete mutation data：
Gene Ontology (GO)
Pathways
• cGMP-PKG signaling pathway (Reactome: R-HSA-418457)
• Phototransduction (KEGG: hsa04744)
• Alzheimer disease (KEGG: hsa05010)
• cGMP metabolic process (GO:0046068)
Protein Summary
PDE9A is a 593-amino acid protein (isoform 1) with a molecular weight of ~67 kDa. It contains a conserved catalytic domain characteristic of class I PDEs. The enzyme exhibits high affinity for cGMP (Km ~0.17 µM) and is insensitive to the PDE5 inhibitor sildenafil. PDE9A is predominantly cytosolic and is expressed in multiple isoforms due to alternative splicing. Its structure includes a GAF domain that may regulate catalytic activity. The protein is involved in cGMP homeostasis in the brain, kidney, and other tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE9A Knockout HEK293 Cell Line | EDJ-KQ5432 | Human | 5152 | Details Get a Quote |
| PDE9A Knockout A-549 Cell Line | EDJ-KQ28604 | Human | 5152 | Details Get a Quote |
| PDE9A Knockout HCT 116 Cell Line | EDJ-KQ28605 | Human | 5152 | Details Get a Quote |
| PDE9A Knockout HeLa Cell Line | EDJ-KQ54106 | Human | 5152 | Details Get a Quote |
