PDE4B
protein-codingphosphodiesterase 4B, the group of Phosphodiesterases
Gene summary
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. The encoded protein regulates the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]
- DPDE4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~582.1 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 PDE4B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002600.4. 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 | 1 | 1 | 3 | 5 | ||
| missense | 41 | 1 | 42 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 1 | 4 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002591.2 | 16 | MANE Select | |
| Ensembl | ENSP00000342637.4 | 16 | MANE Select | |
| RefSeq | NP_001032416.1 | 10 | Standard | |
| RefSeq | NP_001032417.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cAMP signaling pathway - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Morphine addiction - Homo sapiens (human)
- Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
- Glucocorticoid Receptor Pathway
Biological Process
- neutrophil homeostasis
- cAMP catabolic process
- G protein-coupled receptor signaling pathway
- neutrophil chemotaxis
- positive regulation of interferon-gamma production
Molecular Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- protein binding
- cAMP binding
- gamma-tubulin binding
- ion channel binding
Cellular Component
- gamma-tubulin complex
- centrosome
- cytosol
- voltage-gated calcium channel complex
- synaptic vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329654
- Coding exons
- 16
- Length
- 582063
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.77 | 249 | 406 | 0.613 | 0.0000210 | 4916 |
| Missense (PolyPhen) | 76 | 170.54 | 0.44565 | 2095 | ||
| Synonymous | 0.654 | 141 | 151 | 0.932 | 0.00000841 | 1363 |
| Loss of Function | 4.38 | 8 | 36.6 | 0.219 | 0.00000181 | 448 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| 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. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. {ECO:0000269|PubMed:10846163, ECO:0000269|PubMed:15003452}.;
Recessive Scores
- pRec
- 0.407
Intolerance Scores
- LoFtool
- 0.404
- RVIS EVS
- -0.69
- RVIS percentile EVS
- 15.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.644
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |