UGDH

Chr 4AR

UDP-glucose 6-dehydrogenase

Also known as: DEE84, EIEE84, GDH, UDP-GlcDH, UDPGDH, UGD

NCBI Gene: 7358ENSG00000109814UniProt: O60701

The protein encoded by this gene converts UDP-glucose to UDP-glucuronate and thereby participates in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, and cancer growth and metastasis. The expression of this gene is up-regulated by transforming growth factor beta and down-regulated by hypoxia. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 84MIM #618792
AR
117
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UGDH
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 62 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.001
Z-score 2.53
OE 0.41 (0.25–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.30Z-score
OE missense 0.61 (0.53–0.69)
164 obs / 270.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.25–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.53–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 9 / 21.8Missense obs/exp: 164 / 270.7Syn Z: 1.00

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic24
VUS62
Likely Benign11
Benign1
Conflicting1
18
Pathogenic
24
Likely Pathogenic
62
VUS
11
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
16
0
18
Likely Pathogenic
1
21
2
0
24
VUS
0
52
10
0
62
Likely Benign
0
2
1
8
11
Benign
0
0
1
0
1
Conflicting
—1
Total375308117

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UGDH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 84

MIM #618792

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology.
Price MJ et al.·Oncotarget
2023Review
UDP-GlcUA triggers PKR kinase activity to promote liquid-liquid phase separation of TOP2A and enhances radioimmunotherapy resistance.
Yu H et al.·Mol Cell
2025
UDP-glucose dehydrogenase variants cause dystroglycanopathy.
Reelfs AM et al.·Ann Clin Transl Neurol
2025Case report
Hyaluronan in the Tumor Microenvironment.
Spinelli FM et al.·Adv Exp Med Biol
2020Review
Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina.
Martín ME et al.·Seizure
2025Cohort
Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.
Gebru MT et al.·Cancer Res
2025
m6A related metabolic genes in breast cancer and their relationship with prognosis.
Tao Y et al.·Int Immunopharmacol
2025
Phenotypic and genetic characteristics of 24 cases of early infantile epileptic encephalopathy in East China, including a rare case of biallelic UGDH mutations.
Jiang L et al.·Mol Genet Genomic Med
2023Cohort
The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification.
Avendaño-Ortiz J et al.·Infect Immun
2023
Downregulation of UDP-glucose 6-dehydrogenase predicts adverse outcomes in patients with colorectal cancer and promotes tumorigenesis.
Wang M et al.·Sci Rep
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools