PDE4B

Chr 1

phosphodiesterase 4B

Also known as: DPDE4, PDEIVB

NCBI Gene: 5142ENSG00000184588UniProt: Q07343

The protein hydrolyzes cyclic AMP (cAMP), a critical second messenger that regulates numerous physiological processes, and mediates central nervous system effects of various therapeutic agents including antidepressants and anti-inflammatory drugs. Mutations cause autosomal dominant acrodysostosis with hormone resistance, characterized by skeletal dysplasia and resistance to parathyroid hormone and TSH. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.395), indicating intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
91
Pubs (1 yr)
24
P/LP submissions
0%
P/LP missense
0.40
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PDE4B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 48 VUS of 88 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.475
Z-score 4.38
OE 0.22 (0.13–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.77Z-score
OE missense 0.61 (0.55–0.68)
249 obs / 406.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.13–0.40)
0≤0.351.4
Missense OE0.61 (0.55–0.68)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 8 / 36.6Missense obs/exp: 249 / 406.0Syn Z: 0.65
DN
0.6648th %ile
GOF
0.6737th %ile
LOF
0.49top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS48
Likely Benign1
Benign4
22
Pathogenic
2
Likely Pathogenic
48
VUS
1
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
39
9
0
48
Likely Benign
0
0
0
1
1
Benign
0
1
0
3
4
Total04033477

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PDE4B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Berberine Ameliorates Angiotensin II-Induced Endothelial Dysfunction by Blocking AT1R, Inhibiting PDE4b and Activating AKT/eNOS Pathway.
Zhang TY et al.·Chin J Integr Med
2026
Integrated Biochemical and Cellular Validation of SIP0401 as an Isoform-preferential PDE4B Inhibitor.
Alghamdi UM et al.·Mol Biol Rep
2026
PDE4B deficiency aids macrophage differentiation and contributes to Cryptococcus neoformans brain infection.
Gong Y et al.·PLoS Pathog
2026Open Access
Combining Experimental Assays and Molecular Modeling to Evaluate Monosubstituted Cinnamic Acid Derivatives as PDE4B Inhibitors.
Zhao D et al.·ACS Omega
2025Open AccessFunctional
Nerandomilast, a PDE4B inhibitor, alleviates silica-induced lung inflammation and fibrosis by inhibition of NLRP3 inflammasome and TGF-β/Smad signalling.
Wang Y et al.·Br J Pharmacol
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients