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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PAK4
p21 (RAC1) activated kinase 4
Chromosome 19 · 19q13.2
NCBI Gene: 10298Ensembl: ENSG00000130669.18HGNC: HGNC:16059UniProt: O96013
222PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Trending
CLINICAL
Early Pipeline
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of angiogenesisprotein stabilizationplasma membranepositive regulation of focal adhesion disassemblyneurodegenerative diseaseneuroinflammatory disorderneoplasmHereditary breast and ovarian cancer syndrome
✦AI Summary

PAK4 is a serine/threonine kinase that regulates multiple cellular processes including cell migration, survival, and metabolism. PAK4 promotes cancer progression by enhancing tumor cell migration, invasion, and epithelial-mesenchymal transition 1. In colorectal cancer, PAK4 is part of an immune exclusion signature associated with reduced cytotoxic cell infiltration and poor prognosis 2. The kinase also plays a critical role in metabolic regulation by phosphorylating NCoR1, which suppresses fatty acid β-oxidation and ketogenesis through enhanced PPARα repression 3. In glioblastoma, PAK4 is released from migrasomes to promote cell migration and invasion 4. PAK4 contributes to kidney injury by phosphorylating and inactivating glutathione peroxidase 3, leading to increased oxidative stress and impaired fatty acid metabolism 5. The kinase functions through a PAK4-CREB transcriptional axis that regulates diverse cellular programs 6. PAK4 is frequently overexpressed in various cancers, making it an attractive therapeutic target 7. Its dysregulation contributes to pathological conditions by altering cell adhesion, proliferation, and survival pathways.

Sources cited
1
PAK4 promotes tumor cell migration, invasion, and epithelial-mesenchymal transition in cancer
PMID: 40301999
2
PAK4 is part of an immune exclusion signature in colorectal cancer associated with reduced cytotoxic cell infiltration
PMID: 38065082
3
PAK4 phosphorylates NCoR1 to suppress fatty acid β-oxidation and ketogenesis
PMID: 37591884
4
PAK4 is released from migrasomes to promote glioblastoma cell migration and invasion
PMID: 39833606
5
PAK4 phosphorylates and inactivates glutathione peroxidase 3, contributing to kidney ischemia-reperfusion injury
PMID: 40019790
6
PAK4 functions through a PAK4-CREB transcriptional axis regulating diverse cellular programs
PMID: 30755582
7
PAK4 is frequently overexpressed in cancers and represents an attractive therapeutic target
PMID: 34274498
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
neuroinflammatory disorderOpen Targets
0.35Weak
neoplasmOpen Targets
0.12Weak
Hereditary breast and ovarian cancer syndromeOpen Targets
0.12Weak
hereditary breast ovarian cancer syndromeOpen Targets
0.12Weak
prostate cancerOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Weak
osteosarcomaOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.10Suggestive
gliomaOpen Targets
0.10Suggestive
cervical cancerOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.09Suggestive
pachyonychia congenitaOpen Targets
0.09Suggestive
esophageal squamous cell carcinomaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
endometrial cancerOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
PF-03758309Phase I
Serine/threonine-protein kinase PAK 4 inhibitor
Related Genes
CFL1Protein interaction100%ARHGEF6Protein interaction95%PIK3R1Protein interaction93%RHOUProtein interaction93%MAP2K1Protein interaction93%RAF1Protein interaction93%
Tissue Expression6 tissues
Lung
100%
Liver
87%
Ovary
79%
Brain
72%
Bone Marrow
33%
Heart
32%
Gene Interaction Network
Click a node to explore
PAK4CFL1ARHGEF6PIK3R1RHOUMAP2K1RAF1
PROTEIN STRUCTURE
Preparing viewer…
PDB2J0I · 1.60 Å · X-ray
View on RCSB ↗
RankingsWhere PAK4 stands among ~20K protein-coding genes
  • #1,845of 20,598
    Most Researched222 · top 10%
Genes detectedPAK4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors.
PMID: 38065082
Cell · 2023
1.00
2
p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1.
PMID: 37591884
Nat Commun · 2023
0.90
3
Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage.
PMID: 33724154
Virulence · 2021
0.80
4
A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness.
PMID: 33958784
Nat Immunol · 2021
0.72
5
PAK4 signaling in health and disease: defining the PAK4-CREB axis.
PMID: 30755582
Exp Mol Med · 2019
0.70