GALE

Chr 1AR

UDP-galactose-4-epimerase

NCBI Gene: 2582ENSG00000117308UniProt: Q14376

Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids

Primary Disease Associations & Inheritance

Galactose epimerase deficiencyMIM #230350
AR
Thrombocytopenia 13, syndromicMIM #620776
AR
UniProtGalactosemia 3
444
ClinVar variants
66
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GALE
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 119 VUS of 444 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.
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?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.
-0.32Z-score
OE missense 1.06 (0.95–1.19)
217 obs / 204.0 exp
Tolerant

Tolerant to missense variation

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.0.91 (0.62–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.95–1.19)
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.1.00
0≤1.21.6
LoF obs/exp: 16 / 17.5Missense obs/exp: 217 / 204.0Syn Z: 0.01

ClinVar Variant Classifications

444 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic35
VUS119
Likely Benign215
Benign8
Conflicting24
31
Pathogenic
35
Likely Pathogenic
119
VUS
215
Likely Benign
8
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
4
13
0
31
Likely Pathogenic
21
10
4
0
35
VUS
3
92
22
2
119
Likely Benign
0
1
111
103
215
Benign
0
0
8
0
8
Conflicting
—24
Total38107158105432

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

View in ClinVar →

Protein Context — Lollipop Plot

GALE · protein map & ClinVar variants

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

Gene2Phenotype Curations

GALE-related epimerase-deficiency galactosemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Galactose epimerase deficiency

MIM #230350

Molecular basis of disorder known

Autosomal recessive

Thrombocytopenia 13, syndromic

MIM #620776

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary galactosemia.
Demirbas D et al.·Metabolism
2018Review
Pelvic floor physical therapy and mindfulness: approaches for chronic pelvic pain in women-a systematic review and meta-analysis.
Bittelbrunn CC et al.·Arch Gynecol Obstet
2023Meta-analysis
Inappropriate use of statistical power.
Fraser RA·Bone Marrow Transplant
2023
Case-cohort design in hematopoietic cell transplant studies.
Cai J et al.·Bone Marrow Transplant
2022Cohort
[Main parasitic skin disorders].
Bernigaud C et al.·Rev Med Interne
2017Review
Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome.
Shi Y et al.·Adv Sci (Weinh)
2024
Precision medicine: Statistical methods for estimating adaptive treatment strategies.
Moodie EEM et al.·Bone Marrow Transplant
2020
Management of Cooley's anaemia.
Piomelli S·Baillieres Clin Haematol
1993Review
GALE variants associated with syndromic manifestations, macrothrombocytopenia, bleeding, and platelet dysfunction.
Marín-Quílez A et al.·Platelets
2023
Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells.
Lee-Sundlov MM et al.·J Thromb Haemost
2020Review
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