UGDH

Chr 4

UDP-glucose 6-dehydrogenase

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

NCBI Gene: 7358 ENSG00000109814 UniProt: O60701

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.

ResearchSummary from RefSeq, OMIM, Mechanism

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.72

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

26 unique Pathogenic / Likely Pathogenic· 55 VUS of 127 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.41 (0.25–0.72)

0≤0.351.4

Missense OE?0.61 (0.53–0.69)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 9 / 21.8Missense obs/exp: 164 / 270.7Syn Z: 1.00

This gene — mechanism propensity

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

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic24

VUS55

Likely Benign12

Benign1

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	3	21	0	0	24
VUS	1	51	3	0	55
Likely Benign	0	2	1	9	12
Benign	0	0	1	0	1
Conflicting	—				2
Total	6	74	5	9	96

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap UGDH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →