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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NUAK1
NUAK family kinase 1
Chromosome 12 · 12q23.3
NCBI Gene: 9891Ensembl: ENSG00000074590.14HGNC: HGNC:14311UniProt: O60285
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of cellular senescencefibrillar centerprotein serine/threonine kinase activityprotein bindingneurodegenerative diseasetooth diseaseTendinopathysynovium disorder
✦AI Summary

NUAK1 (NUAK family kinase 1) is a serine/threonine protein kinase that plays diverse roles in cellular processes and disease pathogenesis. As a kinase, NUAK1 promotes organ fibrosis through activation of YAP and TGF-β/SMAD signaling pathways, creating a profibrotic feedback loop that drives persistent tissue scarring in kidney, lung, and liver 1. In cancer biology, NUAK1 functions as an oncogenic factor, promoting tumor progression through multiple mechanisms. It enhances cancer cell expansion by activating STAT5/GLI1/SOX2 signaling and contributes to chemotherapy resistance in gastric cancer 2. NUAK1 also mediates drug resistance in non-small cell lung carcinoma by phosphorylating NADK at serine 64, which reduces reactive oxygen species (ROS) accumulation and promotes osimertinib resistance 3. Additionally, NUAK1 can induce immunogenic cell death through ROS production via downregulation of NRF2-mediated antioxidant pathways 4. In diabetic kidney disease, NUAK1 accelerates renal tubular senescence through the ROS/P53 axis, contributing to disease progression 5. Clinical studies demonstrate that elevated NUAK1 expression correlates with poor prognosis in nasopharyngeal carcinoma and other cancers 6, establishing it as both a prognostic biomarker and potential therapeutic target.

Sources cited
1
NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling pathways
PMID: 35320001
2
NUAK1 activates STAT5/GLI1/SOX2 signaling to enhance cancer cell expansion and chemoresistance in gastric cancer
PMID: 38996065
3
NUAK1 phosphorylates NADK at serine 64 to mitigate ROS accumulation and promote osimertinib resistance in NSCLC
PMID: 39159134
4
NUAK1 inhibition induces immunogenic cell death through ROS production via NRF2 downregulation
PMID: 39824180
5
NUAK1 promotes diabetic kidney disease by accelerating renal tubular senescence via the ROS/P53 axis
PMID: 41264843
6
Elevated NUAK1 expression correlates with poor prognosis in nasopharyngeal carcinoma
PMID: 30121842
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.47Moderate
tooth diseaseOpen Targets
0.32Weak
TendinopathyOpen Targets
0.31Weak
synovium disorderOpen Targets
0.31Weak
viral eye infectionOpen Targets
0.30Weak
Dupuytren ContractureOpen Targets
0.28Weak
kidney diseaseOpen Targets
0.26Weak
adolescent idiopathic scoliosisOpen Targets
0.21Weak
vertebral column disorderOpen Targets
0.20Weak
PainOpen Targets
0.19Weak
Abnormality of the skeletal systemOpen Targets
0.19Weak
ovarian dysfunctionOpen Targets
0.19Weak
keratoconusOpen Targets
0.15Weak
ventral herniaOpen Targets
0.15Weak
spinal cord injuryOpen Targets
0.13Weak
gastrointestinal diseaseOpen Targets
0.12Weak
invasive mechanical ventilationOpen Targets
0.12Weak
KeloidOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
STK11Protein interaction93%USP9XProtein interaction89%TP53Protein interaction72%TP53RKShared pathway33%BIRC6Shared pathway20%TFAP2EShared pathway20%
Tissue Expression6 tissues
Heart
100%
Brain
86%
Lung
30%
Ovary
22%
Liver
14%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
NUAK1STK11USP9XTP53TP53RKBIRC6TFAP2E
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O60285
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.64LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.46 [0.34–0.64]
RankingsWhere NUAK1 stands among ~20K protein-coding genes
  • #6,491of 20,598
    Most Researched73
  • #4,538of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedNUAK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling.
PMID: 35320001
Sci Transl Med · 2022
1.00
2
Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity.
PMID: 39824180
Cell Rep Med · 2025
0.90
3
NUAK1-Mediated Phosphorylation of NADK Mitigates ROS Accumulation to Promote Osimertinib Resistance in Non-Small Cell Lung Carcinoma.
PMID: 39159134
Cancer Res · 2024
0.80
4
NUAK: never underestimate a kinase.
PMID: 38939918
Essays Biochem · 2024
0.70
5
NUAK1 activates STAT5/GLI1/SOX2 signaling to enhance cancer cell expansion and drives chemoresistance in gastric cancer.
PMID: 38996065
Cell Rep · 2024
0.60