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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PAK2
p21 (RAC1) activated kinase 2
Chromosome 3 Β· 3q29
NCBI Gene: 5062Ensembl: ENSG00000180370.11HGNC: HGNC:8591UniProt: A8K5M4
276PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
bicellular tight junction assemblynucleusprotein localization to cell-cell junctionpositive regulation of extrinsic apoptotic signaling pathwayKnobloch syndromeKnobloch syndrome 1HIV infectionKnobloch syndrome 2
✦AI Summary

PAK2 is a serine/threonine protein kinase that serves as a downstream effector of small GTPases CDC42 and RAC1, playing crucial roles in multiple cellular processes including cytoskeleton regulation, cell motility, and survival signaling 1. Upon activation by GTP-bound CDC42 and RAC1, PAK2 undergoes conformational changes and autophosphorylation, enabling it to phosphorylate numerous substrates including MAPK4, MAPK6, JUN, and histone H4 1. In cancer contexts, PAK2 promotes cell proliferation and survival through the EGFR-PAK2-ERK5 signaling axis, as demonstrated in hepatocellular carcinoma where FGFR inhibition leads to feedback activation of this pathway 2. PAK2 also regulates RNA methylation by phosphorylating METTL3, promoting its acetylation and spatial control of m6A deposition on chr3-associated RNAs 3. In fibrotic diseases, PAK2 activation drives myofibroblast differentiation and collagen production in idiopathic pulmonary fibrosis, making it a potential therapeutic target 4. Additionally, PAK2 enhances CAR T cell survival by preventing activation-induced cell death 5 and promotes neuroprotection following stroke through the miR-130b-5p/PAK2 signaling pathway, inducing protective endoplasmic reticulum stress 6. These diverse functions position PAK2 as both a therapeutic target in cancer and fibrosis and a protective factor in cellular stress responses.

Sources cited
1
PAK2 is a serine/threonine kinase activated by CDC42 and RAC1 that regulates cancer metastasis
PMID: 39769207
2
PAK2 mediates EGFR-ERK5 signaling in hepatocellular carcinoma and affects lenvatinib response
PMID: 34290403
3
PAK2 phosphorylates METTL3 to promote its acetylation and control m6A RNA methylation
PMID: 40101711
4
PAK2 activation drives myofibroblast differentiation in idiopathic pulmonary fibrosis
PMID: 40675771
5
PAK2 prevents activation-induced cell death and promotes CAR T cell survival
PMID: 39884316
6
PAK2 promotes neuroprotection through miR-130b-5p signaling and endoplasmic reticulum stress
PMID: 39328024
Disease Associationsβ“˜21
Knobloch syndromeOpen Targets
0.45Moderate
Knobloch syndrome 1Open Targets
0.37Weak
HIV infectionOpen Targets
0.37Weak
Knobloch syndrome 2Open Targets
0.35Weak
ovarian carcinomaOpen Targets
0.16Weak
atrial fibrillationOpen Targets
0.14Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
gastric cancerOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
nasopharyngeal carcinomaOpen Targets
0.10Weak
osteosarcomaOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.10Suggestive
melanomaOpen Targets
0.10Suggestive
myocardial infarctionOpen Targets
0.09Suggestive
lymphomaOpen Targets
0.09Suggestive
head and neck squamous cell carcinomaOpen Targets
0.09Suggestive
Miyoshi myopathyOpen Targets
0.09Suggestive
chronic lymphocytic leukemiaOpen Targets
0.08Suggestive
Knobloch syndrome 2UniProt
Pathogenic Variants3
NM_002577.4(PAK2):c.836A>C (p.Gln279Pro)Likely pathogenic
Knobloch syndrome 2
β˜…β˜†β˜†β˜†2024β†’ Residue 279
NM_002577.4(PAK2):c.1273G>A (p.Asp425Asn)Likely pathogenic
Knobloch syndrome 2
β˜…β˜†β˜†β˜†2024β†’ Residue 425
NM_002577.4(PAK2):c.1303G>A (p.Glu435Lys)Pathogenic
Knobloch syndrome
β˜†β˜†β˜†β˜†2004β†’ Residue 435
View on ClinVar β†—
Related Genes
GIT2Protein interaction100%CDC42Protein interaction99%MAP3K1Protein interaction98%ARHGAP10Protein interaction98%VAV1Protein interaction98%NCK1Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
47%
Lung
44%
Liver
39%
Bone Marrow
32%
Ovary
28%
Gene Interaction Network
Click a node to explore
PAK2GIT2CDC42MAP3K1ARHGAP10VAV1NCK1
PROTEIN STRUCTURE
Preparing viewer…
PDB9D51 Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.66LoF Tolerant
pLIβ“˜
0.83Intermediate
Observed/Expected LoF0.14 [0.05–0.66]
RankingsWhere PAK2 stands among ~20K protein-coding genes
  • #1,321of 20,598
    Most Researched276 Β· top 10%
  • #3,915of 5,498
    Most Pathogenic Variants3
  • #4,849of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedPAK2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
EGFR activation limits the response of liver cancer to lenvatinib.
PMID: 34290403
Nature Β· 2021
1.00
2
HIV immune evasin Nef enhances allogeneic CAR T cell potency.
PMID: 39884316
Nature Β· 2025
0.90
3
Integrated spatial and single-cell transcriptomics reveal PAK kinase as a therapeutic target in fibroblastic foci and dense fibrosis of idiopathic pulmonary fibrosis.
PMID: 40675771
Eur Respir J Β· 2025
0.80
4
Cross-species analysis identifies mitochondrial dysregulation as a functional consequence of the schizophrenia-associated 3q29 deletion.
PMID: 37585521
Sci Adv Β· 2023
0.76
5
Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases.
PMID: 38785043
Histopathology Β· 2024
0.72