PDE8B Gene: Phosphodiesterase 8B
A key regulator of cAMP signaling in adrenal and neuroendocrine tissues
Gene Information Card
| Symbol | PDE8B |
|---|---|
| Full Name | Phosphodiesterase 8B |
| Gene Type | Protein-coding |
| Chromosomal Location | 5q13.3 |
| NCBI Gene ID | 8622 ncbi.nlm.nih.gov/gene/8622 |
| Ensembl ID | ENSG00000113231 |
| UniProt ID | O95263 |
| OMIM ID | 603390 |
| HGNC ID | 8784 |
| Aliases | HSPDE8B, PDE8B1, PDE8B2 |
Description
PDE8B encodes a cAMP-specific 3',5'-cyclic nucleotide phosphodiesterase that hydrolyzes cAMP to AMP, playing a critical role in regulating intracellular cAMP levels. The enzyme is highly expressed in the adrenal cortex, thyroid, and brain, and is involved in steroidogenesis, neuroendocrine signaling, and cell proliferation. Mutations in PDE8B are associated with adrenal hyperplasia and Cushing syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cushing syndrome (adrenal) | Loss-of-function mutations reduce cAMP degradation, leading to increased cAMP signaling and cortisol overproduction. | ClinVar, OMIM |
| Adrenocortical adenoma | Somatic mutations in PDE8B may contribute to cAMP pathway activation and tumorigenesis. | COSMIC, literature |
| Primary pigmented nodular adrenocortical disease (PPNAD) | Rare PDE8B variants linked to altered cAMP homeostasis in adrenal nodules. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 58.2 | High |
| Thyroid | 32.1 | Medium |
| Brain (cerebellum) | 25.4 | Medium |
| Testis | 18.7 | Medium |
| Heart | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H295R (adrenocortical) | 45.0 | High expression; model for steroidogenesis |
| SH-SY5Y (neuroblastoma) | 22.5 | Moderate expression; neuronal cAMP regulation |
| HEK293 (embryonic kidney) | 12.3 | Low baseline expression; used for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.914C>T (p.Pro305Leu) | Missense | Rare | Reduced catalytic activity; associated with Cushing syndrome |
| c.1465G>A (p.Glu489Lys) | Missense | Rare | Impaired cAMP hydrolysis; linked to adrenal hyperplasia |
| c.1972C>T (p.Arg658Trp) | Missense | Rare | Loss of function; reported in PPNAD |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro305Leu, p.Glu489Lys) reduce PDE8B enzymatic activity, leading to elevated cAMP and increased cortisol production.
Gain of Function (GOF)
Not reported in PDE8B; gain-of-function would theoretically decrease cAMP and reduce steroidogenesis.
Dominant Negative (DN)
Not documented; PDE8B mutations are typically heterozygous with incomplete penetrance.
View complete mutation data：
Gene Ontology (GO)
| • 3' | • 5'-cyclic-AMP phosphodiesterase activity |
| • cAMP binding | • metal ion binding |
| • signal transduction | • negative regulation of cAMP-mediated signaling |
| • steroid biosynthetic process |
Pathways
• cAMP signaling pathway (Reactome: R-HSA-163615)
• Regulation of cortisol secretion (KEGG: hsa04934)
• G alpha(s) signaling events (Reactome: R-HSA-418555)
Protein Summary
PDE8B is a 733-amino acid protein containing a catalytic domain characteristic of class I phosphodiesterases. It specifically hydrolyzes cAMP with high affinity (Km ~0.15 µM) and is insensitive to the PDE4 inhibitor rolipram. The enzyme is expressed as multiple splice variants (PDE8B1, PDE8B2) with distinct N-terminal regions. PDE8B localizes to the cytoplasm and is involved in feedback regulation of cAMP levels in response to hormonal stimuli, particularly in the adrenal cortex where it modulates ACTH signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDE8B Knockout HEK293 Cell Line | EDJ-KQ6303 | Human | 8622 | Details Get a Quote |
| PDE8B Knockout A-549 Cell Line | EDJ-KQ30209 | Human | 8622 | Details Get a Quote |
| PDE8B Knockout HeLa Cell Line | EDJ-KQ30210 | Human | 8622 | Details Get a Quote |
| PDE8B Knockout HCT 116 Cell Line | EDJ-KQ71909 | Human | 8622 | Details Get a Quote |
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