PDE9A
protein-codingphosphodiesterase 9A, the group of Phosphodiesterases
Gene summary
The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~121.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PDE9A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002606.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 8 | ||||
| missense | 92 | 3 | 1 | 96 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 95 | 11 | 1 | 107 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002597.1 | 20 | MANE Select | |
| Ensembl | ENSP00000291539.6 | 20 | MANE Select | |
| RefSeq | NP_001001567.1 | 19 | Standard | |
| RefSeq | NP_001001568.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Purine metabolism - Homo sapiens (human)
- Phosphodiesterases in neuronal function
- Purine nucleotides nucleosides metabolism
- Hemostasis
- cGMP effects
Biological Process
- signal transduction
- positive regulation of cardiac muscle hypertrophy
- cGMP-mediated signaling
- cGMP metabolic process
- cGMP catabolic process
Molecular Function
- 3',5'-cyclic-nucleotide phosphodiesterase activity
- protein binding
- metal ion binding
- 3',5'-cyclic-GMP phosphodiesterase activity
Cellular Component
- endoplasmic reticulum
- Golgi apparatus
- cytosol
- ruffle membrane
- sarcolemma
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000291539
- Coding exons
- 20
- Length
- 121874
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125748
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.09 | 307 | 365 | 0.840 | 0.0000221 | 3945 |
| Missense (PolyPhen) | 81 | 114.1 | 0.70988 | 1230 | ||
| Synonymous | 0.482 | 133 | 140 | 0.948 | 0.00000962 | 1044 |
| Loss of Function | 4.11 | 12 | 40.1 | 0.300 | 0.00000213 | 440 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP (PubMed:9624146, PubMed:18757755, PubMed:21483814). Specifically regulates natriuretic-peptide- dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (By similarity). {ECO:0000250|UniProtKB:Q8QZV1, ECO:0000269|PubMed:18757755, ECO:0000269|PubMed:21483814, ECO:0000269|PubMed:25799991, ECO:0000269|PubMed:9624146, ECO:0000305}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.262
- RVIS EVS
- -0.46
- RVIS percentile EVS
- 23.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |