UGDH

Chr 4AR

UDP-glucose 6-dehydrogenase

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

NCBI Gene: 7358ENSG00000109814UniProt: O60701OMIM: 603370

The protein converts UDP-glucose to UDP-glucuronate, which is essential for biosynthesis of glycosaminoglycans including hyaluronan, chondroitin sulfate, and heparan sulfate that form critical components of the extracellular matrix. Mutations cause developmental and epileptic encephalopathy 84, inherited in an autosomal recessive pattern. The pathogenic mechanism likely involves loss of function given the autosomal recessive inheritance and the protein's essential role in extracellular matrix formation.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
DNmechanismARLOEUF 0.721 OMIM phenotype
Clinical Summary— UGDH
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 61 VUS of 148 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.001
Z-score 2.53
OE 0.41 (0.25–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
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
LoF OE0.41 (0.25–0.72)
0≤0.351.4
Missense OE0.61 (0.53–0.69)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 9 / 21.8Missense obs/exp: 164 / 270.7Syn Z: 1.00
DN
0.6937th %ile
GOF
0.5660th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic24
VUS61
Likely Benign12
Benign1
Conflicting2
17
Pathogenic
24
Likely Pathogenic
61
VUS
12
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
15
0
17
Likely Pathogenic
3
21
0
0
24
VUS
1
51
9
0
61
Likely Benign
0
2
1
9
12
Benign
0
0
1
0
1
Conflicting
—2
Total674269117

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients