PDE8A
protein-codingphosphodiesterase 8A, the group of Phosphodiesterases|PAS domain containing
Gene summary
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~158.7 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 PDE8A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002605.3. 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 | 2 | 2 | ||||
| missense | 105 | 5 | 110 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 112 | 5 | 0 | 117 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002596.1 | 22 | MANE Select | |
| Ensembl | ENSP00000378056.1 | 22 | MANE Select | |
| RefSeq | NP_001230066.1 | 21 | Standard | |
| RefSeq | NP_775656.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cortisol synthesis and secretion - Homo sapiens (human)
- Cushing,s syndrome - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Morphine addiction - Homo sapiens (human)
- G Protein Signaling Pathways
Biological Process
- positive regulation of protein phosphorylation
- cAMP catabolic process
- regulation of transcription, DNA-templated
- G protein-coupled receptor signaling pathway
- negative regulation of cell death
Molecular Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- kinase binding
- metal ion binding
- 3',5'-cyclic-GMP phosphodiesterase activity
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310298
- Coding exons
- 22
- Length
- 158706
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 377 | 442 | 0.853 | 0.0000231 | 5447 |
| Missense (PolyPhen) | 129 | 178.25 | 0.72372 | 2275 | ||
| Synonymous | 1.60 | 132 | 158 | 0.838 | 0.00000829 | 1544 |
| Loss of Function | 4.00 | 15 | 43.4 | 0.345 | 0.00000228 | 532 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser- 259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF- activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299). {ECO:0000269|PubMed:18983167, ECO:0000269|PubMed:23509299}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.329
- RVIS EVS
- -0.2
- RVIS percentile EVS
- 39.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.748
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |