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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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UGDH
UDP-glucose 6-dehydrogenase
Chromosome 4 Β· 4p14
NCBI Gene: 7358Ensembl: ENSG00000109814.13HGNC: HGNC:12525UniProt: O60701
132PubMed Papers
21Diseases
0Drugs
27Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
UDP-glucose 6-dehydrogenase activityprotein hexamerizationidentical protein bindingneuron developmentdevelopmental and epileptic encephalopathy, 84Epileptic encephalopathygenetic disorderneurodegenerative disease
✦AI Summary

UGDH (UDP-glucose 6-dehydrogenase) is a cytosolic hexameric enzyme that catalyzes the conversion of UDP-glucose to UDP-glucuronic acid (UDP-GlcUA), a critical metabolic step with dual roles in normal physiology and disease 1. Primary function: UGDH is essential for biosynthesis of complex glycosaminoglycans including chondroitin sulfate and heparan sulfate, and is required for proper embryonic development and brain/neuronal development 2. Mechanism: The enzyme catalyzes two NAD+-dependent oxidation reactions converting the C6 hydroxyl of UDP-glucose to a carboxylate, generating UDP-GlcUA required for hyaluronan, proteoglycans, and glucuronide conjugate production 2. Disease relevance: Biallelic UGDH variants cause developmental and epileptic encephalopathy (DEE) with reported effects on cardiac valve and brain development, and dystroglycanopathy 2. Clinical significance: UGDH is upregulated in multiple cancer types and promotes tumor progression through multiple mechanisms: tyrosine phosphorylation enhances lung cancer metastasis 3, while post-translational modifications (lactylation, O-GlcNAcylation) regulate its activity and extracellular matrix remodeling to suppress anti-tumor immunity [PMID:40150862; 47]. UGDH expression correlates with chemotherapy resistance in colorectal and hepatocellular carcinoma [PMID:40311992; 54], positioning it as both a prognostication marker and therapeutic target in oncology.

Sources cited
1
UGDH catalyzes NAD+-dependent oxidation of UDP-glucose C6 hydroxyl to carboxylate, generating UDP-GlcUA required for hyaluronan, proteoglycans, and detoxification; biallelic variants cause developmental and epileptic encephalopathy
PMID: 40879729
2
UGDH is a cytosolic hexameric enzyme converting UDP-glucose to UDP-GlcUA; classified as molecular indicator of tumor progression in multiple cancer types
PMID: 37769033
3
UGDH phosphorylation at tyrosine 473 promotes lung cancer metastasis by enhancing SNAI1 mRNA stability and epithelial-mesenchymal transition
PMID: 31243371
4
UGDH lactylation at K6 suppresses glycosaminoglycan synthesis and activates MAPK signaling, exacerbating osteoarthritis progression
PMID: 40150862
5
UGDH O-GlcNAcylation at serine 350 enhances enzymatic activity and hyaluronic acid synthesis while suppressing CD8+ T cell infiltration through STAT1 pathway inhibition
PMID: 41053177
6
UGDH promotes 5-fluorouracil resistance in colorectal cancer via PI3K/AKT-EEF1A2-PRDX1 pathway by clearing ROS and inhibiting apoptosis
PMID: 40311992
7
UDP-GlcUA produced by UGDH activates PKR kinase post-radiation, promoting TOP2A phase separation and enhancing radioimmunotherapy resistance in hepatocellular carcinoma
PMID: 41202804
Disease Associationsβ“˜21
developmental and epileptic encephalopathy, 84Open Targets
0.78Strong
Epileptic encephalopathyOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.41Moderate
neurodegenerative diseaseOpen Targets
0.35Weak
infantile spasmsOpen Targets
0.27Weak
hemorrhoidOpen Targets
0.26Weak
neuroinflammatory disorderOpen Targets
0.25Weak
color vision disorderOpen Targets
0.25Weak
neoplasmOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
non-alcoholic steatohepatitisOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
gliomaOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
microphthalmia with limb anomaliesOpen Targets
0.04Suggestive
Developmental and epileptic encephalopathy 84UniProt
Pathogenic Variants27
NM_003359.4(UGDH):c.193C>T (p.Arg65Ter)Pathogenic
Developmental and epileptic encephalopathy, 84|Epileptic encephalopathy|UGDH-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NM_003359.4(UGDH):c.131C>T (p.Ala44Val)Pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84|West syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 44
NM_003359.4(UGDH):c.950G>A (p.Arg317Gln)Pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84
β˜…β˜…β˜†β˜†2022β†’ Residue 317
NM_003359.4(UGDH):c.742G>C (p.Val248Leu)Likely pathogenic
Developmental and epileptic encephalopathy, 84
β˜…β˜†β˜†β˜†2025β†’ Residue 248
NM_003359.4(UGDH):c.1084G>A (p.Ala362Thr)Likely pathogenic
Developmental and epileptic encephalopathy, 84
β˜…β˜†β˜†β˜†2025β†’ Residue 362
NM_003359.4(UGDH):c.1038-2A>GPathogenic
Developmental and epileptic encephalopathy, 84
β˜…β˜†β˜†β˜†2024
NM_003359.4(UGDH):c.1270del (p.Asp424fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 424
NM_003359.4(UGDH):c.1177C>T (p.Arg393Trp)Likely pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84
β˜…β˜†β˜†β˜†2023β†’ Residue 393
NM_003359.4(UGDH):c.528_531del (p.Asp176fs)Likely pathogenic
Developmental and epileptic encephalopathy, 84
β˜…β˜†β˜†β˜†2022β†’ Residue 176
NM_003359.4(UGDH):c.214T>G (p.Ser72Ala)Pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84
β˜†β˜†β˜†β˜†2020β†’ Residue 72
NM_003359.4(UGDH):c.244G>A (p.Ala82Thr)Pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84
β˜†β˜†β˜†β˜†2020β†’ Residue 82
NM_003359.4(UGDH):c.1100A>G (p.Tyr367Cys)Pathogenic
Epileptic encephalopathy|Developmental and epileptic encephalopathy, 84
β˜†β˜†β˜†β˜†2020β†’ Residue 367
NM_003359.4(UGDH):c.1346A>G (p.His449Arg)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 449
NM_003359.4(UGDH):c.125T>C (p.Ile42Thr)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 42
NM_003359.4(UGDH):c.70G>A (p.Ala24Thr)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 24
NM_003359.4(UGDH):c.374T>C (p.Ile125Thr)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 125
NM_003359.4(UGDH):c.1328G>A (p.Arg443His)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 443
NM_003359.4(UGDH):c.1324C>T (p.Arg442Trp)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 442
NM_003359.4(UGDH):c.1228G>T (p.Ala410Ser)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 410
NM_003359.4(UGDH):c.1068T>G (p.Tyr356Ter)Likely pathogenic
Epileptic encephalopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 356
View on ClinVar β†—
Related Genes
UGT1A9Protein interaction100%UGT1A3Protein interaction100%UGT1A1Protein interaction100%UGT1A8Protein interaction100%UGT1A4Protein interaction100%UGT1A10Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Ovary
21%
Lung
17%
Heart
12%
Brain
6%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
UGDHUGT1A9UGT1A3UGT1A1UGT1A8UGT1A4UGT1A10
PROTEIN STRUCTURE
Preparing viewer…
PDB2Q3E Β· 2.00 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.90LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.67 [0.50–0.90]
RankingsWhere UGDH stands among ~20K protein-coding genes
  • #3,543of 20,598
    Most Researched132 Β· top quartile
  • #1,890of 5,498
    Most Pathogenic Variants27
  • #8,161of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedUGDH
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis.
PMID: 31243371
Nature Β· 2019
1.00
2
UGDH Lactylation Aggravates Osteoarthritis by Suppressing Glycosaminoglycan Synthesis and Orchestrating Nucleocytoplasmic Transport to Activate MAPK Signaling.
PMID: 40150862
Adv Sci (Weinh) Β· 2025
0.90
3
Disruption of sugar nucleotide clearance is a therapeutic vulnerability of cancer cells.
PMID: 37880368
Nature Β· 2023
0.80
4
UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology.
PMID: 37769033
Oncotarget Β· 2023
0.70
5
Recent insights into the implications of UGDH mutations for human developmental disease.
PMID: 40879729
Biochem Soc Trans Β· 2025
0.60