GALE

Chr 1AR

UDP-galactose-4-epimerase

Also known as: SDR1E1, THC13

NCBI Gene: 2582 ENSG00000117308 UniProt: Q14376 OMIM: 606953

The encoded UDP-galactose-4-epimerase catalyzes the epimerization of UDP-glucose to UDP-galactose and UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine, making cells dependent on both exogenous galactose and N-acetylgalactosamine for glycoprotein and glycolipid synthesis. Mutations cause autosomal recessive epimerase-deficiency galactosemia (galactosemia type 3), characterized by liver damage, early-onset cataracts, deafness, and cognitive disability with variable severity from mild peripheral to severe generalized forms. Mutations also cause thrombocytopenia 13, syndromic.

OMIM ResearchSummary from RefSeq, OMIM, Mechanism

This gene encodes UDP-galactose-4-epimerase which catalyzes two distinct but analogous reactions: the epimerization of UDP-glucose to UDP-galactose, and the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The bifunctional nature of the enzyme has the important metabolic consequence that mutant cells (or individuals) are dependent not only on exogenous galactose, but also on exogenous N-acetylgalactosamine as a necessary precursor for the synthesis of glycoproteins and glycolipids. Mutations in this gene result in epimerase-deficiency galactosemia, also referred to as galactosemia type 3, a disease characterized by liver damage, early-onset cataracts, deafness and cognitive disability, with symptoms ranging from mild ('peripheral' form) to severe ('generalized' form). Multiple alternatively spliced transcripts encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.392 OMIM phenotypes

Clinical Summary— GALE

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Gene-Disease Validity (ClinGen)

galactose epimerase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

61 unique Pathogenic / Likely Pathogenic· 115 VUS of 435 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.39LOEUF

pLI 0.000

Z-score 0.33

OE 0.91 (0.62–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.06 (0.95–1.19)

217 obs / 204.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.62–1.39)

0≤0.351.4

Missense OE?1.06 (0.95–1.19)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 16 / 17.5Missense obs/exp: 217 / 204.0Syn Z: 0.01

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGALE-related epimerase-deficiency galactosemiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6936th %ile

GOF

0.4677th %ile

LOF

0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

435 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic35

VUS115

Likely Benign215

Benign8

Conflicting24

Pathogenic

Likely Pathogenic

115

VUS

215

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	19	4	3	0	26
Likely Pathogenic	25	10	0	0	35
VUS	3	96	13	3	115
Likely Benign	0	1	111	103	215
Benign	0	0	8	0	8
Conflicting	—				24
Total	47	111	135	106	423

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap GALE — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →