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GeneE
50 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.
PAK1
p21 (RAC1) activated kinase 1
Chromosome 11 Β· 11q13.5-q14.1
NCBI Gene: 5058Ensembl: ENSG00000149269.10HGNC: HGNC:8590UniProt: B3KNX7
573PubMed Papers
21Diseases
0Drugs
25Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein kinase activitynegative regulation of cell proliferation involved in contact inhibitionpositive regulation of stress fiber assemblyhepatocyte growth factor receptor signaling pathwayintellectual developmental disorder with macrocephaly, seizures, and speech delayNeurodevelopmental disordergenetic disorderMyoclonus
✦AI Summary

PAK1 (p21-activated kinase 1) is a serine/threonine protein kinase that functions as a critical hub in intracellular signaling downstream of integrins and receptor tyrosine kinases 12. Activated by CDC42 and RAC1 GTPases 34, PAK1 regulates cytoskeleton dynamics, cell adhesion, migration, and proliferation through phosphorylation of substrates including MAP2K1, RAF1, and cofilin 56. PAK1 also promotes autophagy by phosphorylating ATG5, a process enhanced by hypoxia-induced acetylation 7. PAK1 dysregulation is implicated in multiple cancers and neurological disorders. In glioblastoma, elevated PAK1 promotes autophagy and tumor growth; PAK1 inhibition with FRAX597 blocks these processes 7. PAK1 overexpression in bladder cancer correlates with tumor size, histological grade, and metastasis; PAK1 knockdown reduces proliferation and invasion 8. In prostate cancer, PAK1 drives androgen receptor signaling inhibitor cross-resistance through the PAK1/RELA/hnRNPA1/AR-V7 axis 9. Melanoma therapy resistance involves PAK1-mediated evasion of cell death and immunosuppression 10. In Down syndrome, elevated DSCAM/PAK1 pathway activity impairs neurogenesis; pathway suppression rescues cortical organoid development 11. PAK1 represents a tractable therapeutic target across multiple disease contexts 1213.

Sources cited
1
PAK1 also promotes autophagy by phosphorylating ATG5, a process enhanced by hypoxia-induced acetylation .
PMID: 32186433
2
PAK1 overexpression in bladder cancer correlates with tumor size, histological grade, and metastasis; PAK1 knockdown reduces proliferation and invasion .
PMID: 25412958
3
In prostate cancer, PAK1 drives androgen receptor signaling inhibitor cross-resistance through the PAK1/RELA/hnRNPA1/AR-V7 axis .
PMID: 38364963
4
Melanoma therapy resistance involves PAK1-mediated evasion of cell death and immunosuppression .
PMID: 37830586
5
In Down syndrome, elevated DSCAM/PAK1 pathway activity impairs neurogenesis; pathway suppression rescues cortical organoid development .
PMID: 33945512
Disease Associationsβ“˜21
intellectual developmental disorder with macrocephaly, seizures, and speech delayOpen Targets
0.71Strong
Neurodevelopmental disorderOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.34Weak
MyoclonusOpen Targets
0.25Weak
drug allergyOpen Targets
0.25Weak
multinodular goiterOpen Targets
0.22Weak
joint diseaseOpen Targets
0.22Weak
cutaneous melanomaOpen Targets
0.19Weak
neurodegenerative diseaseOpen Targets
0.17Weak
schizophreniaOpen Targets
0.13Weak
neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotoniaOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
glioblastoma multiformeOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Suggestive
cancerOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.09Suggestive
Intellectual developmental disorder with macrocephaly, seizures, and speech delayUniProt
Pathogenic Variants25
NM_002576.5(PAK1):c.362C>T (p.Pro121Leu)Pathogenic
PAK1-related neurodevelopmental disorders|not provided|PAK1-related disorder|Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜…β˜†β˜†2024β†’ Residue 121
NM_002576.5(PAK1):c.1409T>G (p.Leu470Arg)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜…β˜†β˜†2023β†’ Residue 470
NM_002576.5(PAK1):c.1427T>C (p.Ile476Thr)Pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay|See cases|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 476
NM_002576.5(PAK1):c.361C>T (p.Pro121Ser)Pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 121
NM_002576.5(PAK1):c.428T>C (p.Met143Thr)Likely pathogenic
not provided|Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜…β˜†β˜†2021β†’ Residue 143
NM_002576.5(PAK1):c.1115A>C (p.Glu372Ala)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2025β†’ Residue 372
NM_002576.5(PAK1):c.209_212del (p.Lys70fs)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2024β†’ Residue 70
NM_002576.5(PAK1):c.427A>G (p.Met143Val)Likely pathogenic
PAK1-related disorder|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 143
NM_002576.5(PAK1):c.1261C>T (p.Arg421Trp)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 421
NM_002576.5(PAK1):c.391T>A (p.Tyr131Asn)Pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2022β†’ Residue 131
NM_002576.5(PAK1):c.424T>C (p.Tyr142His)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2022β†’ Residue 142
NM_002576.5(PAK1):c.1409T>A (p.Leu470Gln)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2022β†’ Residue 470
NM_002576.5(PAK1):c.1420T>C (p.Tyr474His)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2021β†’ Residue 474
NM_002576.5(PAK1):c.428T>A (p.Met143Lys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 143
NM_002576.5(PAK1):c.328T>A (p.Ser110Thr)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2019β†’ Residue 110
NM_002576.5(PAK1):c.397T>C (p.Ser133Pro)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay|not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 133
NM_002576.5(PAK1):c.392A>G (p.Tyr131Cys)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†2019β†’ Residue 131
NM_002576.5(PAK1):c.1286A>G (p.Tyr429Cys)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay|not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 429
NM_002576.5(PAK1):c.850G>A (p.Val284Met)Likely pathogenic
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
β˜…β˜†β˜†β˜†β†’ Residue 284
NM_002576.5(PAK1):c.262G>A (p.Gly88Ser)Likely pathogenic
PAK1-related disorder
β˜†β˜†β˜†β˜†2023β†’ Residue 88
View on ClinVar β†—
Related Genes
GRB2Protein interaction100%GIT2Protein interaction100%RAF1Protein interaction100%CDC42Protein interaction100%NCK1Protein interaction99%MAP2K1Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
42%
Ovary
22%
Lung
15%
Liver
9%
Heart
9%
Gene Interaction Network
Click a node to explore
PAK1GRB2GIT2RAF1CDC42NCK1MAP2K1
PROTEIN STRUCTURE
Preparing viewer…
PDB3FXZ Β· 1.64 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.70LoF Tolerant
pLIβ“˜
0.06Tolerant
Observed/Expected LoF0.46 [0.31–0.70]
RankingsWhere PAK1 stands among ~20K protein-coding genes
  • #418of 20,598
    Most Researched573 Β· top 5%
  • #1,961of 5,498
    Most Pathogenic Variants25
  • #5,380of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedPAK1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome.
PMID: 33945512
J Clin Invest Β· 2021
1.00
2
Targeting PAK1.
PMID: 28202661
Biochem Soc Trans Β· 2017
0.90
3
PRMT5-PAK1 Signaling Participates in Metastasis and Is Associated With Poor Prognosis in Human Esophageal Carcinoma.
PMID: 38307587
Anticancer Res Β· 2024
0.88
4
Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases.
PMID: 38785043
Histopathology Β· 2024
0.84
5
Pak1 gene functioned differentially in different BCR-ABL subtypes in leukemiagenesis and treatment response through STAT5 pathway.
PMID: 30784762
Leuk Res Β· 2019
0.82