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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NAGK
N-acetylglucosamine kinase
Chromosome 2 · 2p13.3
NCBI Gene: 55577Ensembl: ENSG00000124357.13HGNC: HGNC:17174UniProt: A0A384N6G7
88PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to muramyl dipeptidedefense response to bacteriumpositive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathwaymuramyl dipeptide kinase activityneurodegenerative diseaseresponse to xenobiotic stimulusneoplasmMODY
✦AI Summary

NAGK (N-acetylglucosamine kinase) is a multifunctional enzyme with both metabolic and regulatory roles. Its primary function involves converting N-acetylglucosamine (GlcNAc) to GlcNAc 6-phosphate, contributing to hexosamine salvage pathways that support tumor growth 1. NAGK plays a crucial role in maintaining UDP-GlcNAc pools when glutamine is limited, with elevated expression observed in pancreatic ductal adenocarcinoma where its deletion impairs tumor growth 1. The enzyme is subject to complex post-translational regulation through phosphorylation and pyrophosphorylation at serine 76, which significantly reduces its kinase activity and alters protein-protein interactions 2. Beyond its canonical metabolic function, NAGK exhibits non-canonical structural roles in neuronal development, promoting dendritic complexity and branching through interactions with proteins like SNRPN and dynein-mediated microtubule transport 34. NAGK has therapeutic relevance in neurodevelopmental disorders, as it can rescue impaired axodendritic development in Prader-Willi syndrome patient-derived neurons 4. Clinically, NAGK serves as a reference gene for detecting MYCN amplification in neuroblastoma patients through plasma-based qPCR assays 5.

Sources cited
1
NAGK converts GlcNAc to GlcNAc 6-phosphate in hexosamine salvage pathways and supports tumor growth in pancreatic cancer
PMID: 34844667
2
NAGK activity is regulated by phosphorylation and pyrophosphorylation at serine 76, which reduces kinase activity and alters protein interactions
PMID: 38733353
3
NAGK has non-canonical functions in promoting neuronal dendritic complexity and branching
PMID: 24625575
4
NAGK interacts with SNRPN and dynein proteins to promote axodendritic development and can rescue neurodevelopmental defects in Prader-Willi syndrome
PMID: 37511433
5
NAGK serves as a reference gene for detecting MYCN amplification in neuroblastoma patients through plasma-based qPCR assays
PMID: 32896084
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.20Weak
response to xenobiotic stimulusOpen Targets
0.12Weak
neoplasmOpen Targets
0.08Suggestive
MODYOpen Targets
0.06Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
diabetes mellitus, permanent neonatal 4Open Targets
0.05Suggestive
Patent ductus arteriosusOpen Targets
0.05Suggestive
diabetes mellitus, transient neonatal, 3Open Targets
0.04Suggestive
male reproductive organ cancerOpen Targets
0.04Suggestive
maturity-onset diabetes of the young type 13Open Targets
0.04Suggestive
permanent neonatal diabetes mellitus 1Open Targets
0.04Suggestive
Nijmegen breakage syndromeOpen Targets
0.03Suggestive
congenital enteropathy due to enteropeptidase deficiencyOpen Targets
0.03Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.03Suggestive
amegakaryocytic thrombocytopenia, congenital, 2Open Targets
0.03Suggestive
Recurrent infection due to specific granule deficiencyOpen Targets
0.03Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.03Suggestive
diarrhea 13Open Targets
0.03Suggestive
congenital lethal erythrodermaOpen Targets
0.03Suggestive
Aplasia cutis congenita - intestinal lymphangiectasiaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GFPT1Protein interaction98%PGM3Protein interaction98%CHIT1Protein interaction91%HEXAProtein interaction91%HEXBProtein interaction91%RENBPProtein interaction91%
Tissue Expression6 tissues
Ovary
100%
Lung
91%
Bone Marrow
71%
Liver
54%
Heart
47%
Brain
32%
Gene Interaction Network
Click a node to explore
NAGKGFPT1PGM3CHIT1HEXAHEXBRENBP
PROTEIN STRUCTURE
Preparing viewer…
PDB2CH5 · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.81 [0.62–1.07]
RankingsWhere NAGK stands among ~20K protein-coding genes
  • #5,426of 20,598
    Most Researched88
  • #10,838of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedNAGK
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth.
PMID: 40249802
Sci Adv · 2025
1.00
2
Glutamine deprivation triggers NAGK-dependent hexosamine salvage.
PMID: 34844667
Elife · 2021
0.90
3
Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma.
PMID: 32896084
Mol Oncol · 2020
0.80
4
The P
PMID: 30483512
Front Mol Biosci · 2018
0.70
5
An Uncommon Phosphorylation Mode Regulates the Activity and Protein Interactions of
PMID: 38733353
J Am Chem Soc · 2024
0.60