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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PAK6
p21 (RAC1) activated kinase 6
Chromosome 15 · 15q15.1
NCBI Gene: 56924Ensembl: ENSG00000137843.13HGNC: HGNC:16061UniProt: Q9NQU5
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmcadherin bindingfibrillar centerprotein bindingmosaic variegated aneuploidy syndrome 1premature chromatid separation traitneuroinflammatory disordergenetic disorder
✦AI Summary

PAK6 is a serine-threonine kinase with brain-enriched physiological expression that functions as a multifaceted signaling regulator across neuronal and cancer contexts. Mechanistically, PAK6 operates through protein-protein interactions and phosphorylation of downstream substrates including 14-3-3 proteins, MAPK14, and DNA repair machinery. In neural tissue, PAK6 localizes to centrosomes and cilia where it positively regulates ciliogenesis 1. Notably, PAK6 rescues ciliogenesis defects caused by the G2019S LRRK2 Parkinson's disease mutation in a mutation-specific manner by binding the Roc-COR domain, making it the first identified LRRK2 modifier with PD mutation-specificity 1. In cancer pathogenesis, PAK6 is dysregulated through multiple mechanisms: androgen receptor-mediated activation promotes prostate cancer cell motility and invasion 2, METTL3-dependent m6A modification stabilizes PAK6 mRNA to drive cervical cancer progression via MAPK14 phosphorylation 3, and PAK6 enhances gastric cancer chemoresistance by promoting homologous recombination DNA repair through ATR/CHK1 signaling activation 4. Clinically, elevated PAK6 expression correlates with poor prognosis, including advanced cancer stages and chemotherapy resistance 4. Additionally, urinary exosomal PAK6 serves as a noninvasive diagnostic biomarker for diabetic nephropathy with area under curve of 0.903 5, and PAK6 expression associates with drug sensitivity in T-cell prolymphocytic leukemia 6.

Sources cited
1
PAK6 localizes at centrosome and cilium, positively regulates ciliogenesis in neurons and astrocytes, and rescues G2019S but not R1441C LRRK2 mutation-associated ciliogenesis and centrosomal cohesion defects
PMID: 39419978
2
METTL3-mediated m6A modification stabilizes PAK6 mRNA through IGF2BP1 recognition; PAK6 phosphorylates MAPK14 at Ser56 to drive cervical cancer proliferation, migration and invasion
PMID: 40194572
3
Androgen receptor directly interacts with and activates PAK6; androgen-stimulated PAK6 activation promotes prostate cancer cell motility and invasion
PMID: 24130878
4
PAK6 enhances gastric cancer chemoresistance to oxaliplatin by promoting homologous recombination through ATR/CHK1 signaling and RAD51 recruitment; high PAK6 correlates with poor prognosis and therapy resistance
PMID: 35902562
5
Urinary exosomal PAK6 levels negatively correlate with glomerular filtration rate and positively with serum creatinine; PAK6 achieves AUC of 0.903 for diabetic nephropathy diagnosis
PMID: 37789280
6
Elevated PAK6 expression is associated with sensitivity to STAT3/STAT5 degraders in T-prolymphocytic leukemia
PMID: 40234614
Disease Associationsⓘ20
mosaic variegated aneuploidy syndrome 1Open Targets
0.52Moderate
premature chromatid separation traitOpen Targets
0.27Weak
neuroinflammatory disorderOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
colorectal cancerOpen Targets
0.18Weak
intestinal obstructionOpen Targets
0.12Weak
keratoconusOpen Targets
0.11Weak
microcephalyOpen Targets
0.11Weak
hypertrophic cardiomyopathyOpen Targets
0.11Weak
prostate cancerOpen Targets
0.10Suggestive
Parkinson diseaseOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
colon carcinomaOpen Targets
0.07Suggestive
small cell lung carcinomaOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.06Suggestive
chronic myelogenous leukemiaOpen Targets
0.06Suggestive
cervical cancerOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IQGAP1Protein interaction98%ARProtein interaction96%RAC2Protein interaction94%ARHGEF6Protein interaction94%LIMK1Protein interaction94%LIMK2Protein interaction94%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
45%
Brain
10%
Lung
1%
Ovary
1%
Liver
0%
Gene Interaction Network
Click a node to explore
PAK6IQGAP1ARRAC2ARHGEF6LIMK1LIMK2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NQU5
View on AlphaFold ↗
RankingsWhere PAK6 stands among ~20K protein-coding genes
  • #6,492of 20,598
    Most Researched73
Genes detectedPAK6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner.
PMID: 39419978
Cell Death Dis · 2024
1.00
2
METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14.
PMID: 40194572
Int J Biol Macromol · 2025
0.90
3
Direct interaction between AR and PAK6 in androgen-stimulated PAK6 activation.
PMID: 24130878
PLoS One · 2013
0.80
4
Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells.
PMID: 35969127
Biochem J · 2022
0.70
5
[Cloning of human PAK6 cDNA, preparation of anti-PAK6 polyclonal antibody and PAK6 expression in prostate cancer].
PMID: 17584649
Nan Fang Yi Ke Da Xue Xue Bao · 2007
0.60