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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PDE4DIP
phosphodiesterase 4D interacting protein
Chromosome 1 · 1q21.2
NCBI Gene: 9659Ensembl: ENSG00000178104.22HGNC: HGNC:15580UniProt: A0A075B749
90PubMed Papers
20Diseases
0Drugs
3Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmolecular adaptor activityregulation of Golgi organizationGolgi apparatusMastocytosisneurodegenerative diseaseCOVID-19macrovascular complications of diabetes
✦AI Summary

PDE4DIP (phosphodiesterase 4D interacting protein) is a Golgi/centrosome-associated scaffolding protein that regulates microtubule dynamics and intracellular signaling compartmentalization. As a component of the AKAP9 complex, PDE4DIP recruits CAMSAP2 to the Golgi apparatus to tether non-centrosomal microtubules, facilitating polarized cell movement 12. At the centrosome, PDE4DIP cooperates with AKAP9, EB1/MAPRE1, and CDK5RAP2 to nucleate and extend microtubules, supporting directed cell migration and mitotic spindle orientation 3. In cardiac tissue, PDE4DIP anchors phosphodiesterase enzymes to regulate cAMP signaling microdomains, controlling heart rate, conduction velocity, and excitation-contraction coupling 4. Inherited PDE4DIP mutations impair PKA compartmentalization and cause early-onset atrial fibrillation with conduction disease, particularly through epistatic interaction with desmin mutations 5. PDE4DIP dysfunction also contributes to left ventricular non-compaction cardiomyopathy via dysregulation of the Rho-ROCK pathway 6. PDE4DIP is oncogenic in lung and colorectal cancers. In non-small cell lung cancer, PDE4DIP overexpression promotes cell proliferation by stabilizing PKA RIIα at the Golgi, suppressing apoptosis 7. In colorectal cancer, PDE4DIP enhances RAS/ERK signaling by suppressing the RasGAP neurofibromin through PKCε-mediated degradation, conferring MEK inhibitor resistance 8. Genomic variants in PDE4DIP associate with atrial fibrillation, stroke, and heart failure 49.

Sources cited
1
At the centrosome, PDE4DIP cooperates with AKAP9, EB1/MAPRE1, and CDK5RAP2 to nucleate and extend microtubules, supporting directed cell migration and mitotic spindle orientation .
PMID: 29162697
2
In cardiac tissue, PDE4DIP anchors phosphodiesterase enzymes to regulate cAMP signaling microdomains, controlling heart rate, conduction velocity, and excitation-contraction coupling .
PMID: 35346821
3
Inherited PDE4DIP mutations impair PKA compartmentalization and cause early-onset atrial fibrillation with conduction disease, particularly through epistatic interaction with desmin mutations .
PMID: 34289528
4
PDE4DIP dysfunction also contributes to left ventricular non-compaction cardiomyopathy via dysregulation of the Rho-ROCK pathway .
PMID: 40612665
5
In non-small cell lung cancer, PDE4DIP overexpression promotes cell proliferation by stabilizing PKA RIIα at the Golgi, suppressing apoptosis .
PMID: 39905234
6
In colorectal cancer, PDE4DIP enhances RAS/ERK signaling by suppressing the RasGAP neurofibromin through PKCε-mediated degradation, conferring MEK inhibitor resistance .
PMID: 37355626
Disease Associationsⓘ20
MastocytosisOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.30Weak
COVID-19Open Targets
0.26Weak
macrovascular complications of diabetesOpen Targets
0.23Weak
non-small cell lung carcinomaOpen Targets
0.21Weak
acute myeloid leukemiaOpen Targets
0.19Weak
esophageal squamous cell carcinomaOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.19Weak
astrocytomaOpen Targets
0.19Weak
head and neck squamous cell carcinomaOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
soft tissue sarcomaOpen Targets
0.19Weak
melanomaOpen Targets
0.19Weak
urinary bladder carcinomaOpen Targets
0.19Weak
hepatocellular carcinomaOpen Targets
0.19Weak
adrenal cortex carcinomaOpen Targets
0.19Weak
cervical squamous cell carcinomaOpen Targets
0.19Weak
colon adenocarcinomaOpen Targets
0.19Weak
esophageal carcinomaOpen Targets
0.19Weak
gastrointestinal stromal tumorOpen Targets
0.19Weak
Pathogenic Variants3
NM_001395426.1(PDE4DIP):c.4630A>G (p.Ile1544Val)Likely pathogenic
See cases|not provided
★☆☆☆2021→ Residue 1544
NM_001395426.1(PDE4DIP):c.3874C>T (p.Arg1292Cys)Likely pathogenic
See cases
★☆☆☆2021→ Residue 1292
NM_001395426.1(PDE4DIP):c.835-7507G>APathogenic
See cases
★☆☆☆2021
View on ClinVar ↗
Related Genes
AKAP9Protein interaction99%MAPRE1Protein interaction99%PRKACBProtein interaction99%PDE4DProtein interaction83%MYBPC3Protein interaction77%MAPRE3Protein interaction73%
Tissue Expression6 tissues
Heart
100%
Brain
39%
Lung
22%
Liver
18%
Ovary
5%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
PDE4DIPAKAP9MAPRE1PRKACBPDE4DMYBPC3MAPRE3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5VU43
View on AlphaFold ↗
RankingsWhere PDE4DIP stands among ~20K protein-coding genes
  • #5,326of 20,598
    Most Researched90
  • #4,002of 5,498
    Most Pathogenic Variants3
Genes detectedPDE4DIP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PDE4DIP in health and diseases.
PMID: 35346821
Cell Signal · 2022
1.00
2
The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.
PMID: 39905234
Commun Biol · 2025
0.90
3
PDE4DIP contributes to colorectal cancer growth and chemoresistance through modulation of the NF1/RAS signaling axis.
PMID: 37355626
Cell Death Dis · 2023
0.80
4
Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes.
PMID: 36691064
J Neuroinflammation · 2023
0.70
5
Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction.
PMID: 34289528
Hum Mutat · 2021
0.60