GALC

Chr 14AR

galactosylceramidase

NCBI Gene: 2581ENSG00000054983UniProt: P54803

This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Krabbe diseaseMIM #245200
AR
1650
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— GALC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1650 total variants — no pathogenic classifications of 1650 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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.
0.94LOEUF
pLI 0.000
Z-score 1.88
OE 0.69 (0.51–0.94)
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.
0.19Z-score
OE missense 0.97 (0.89–1.06)
365 obs / 375.1 exp
Tolerant

Mild missense constraint

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.0.69 (0.51–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.06)
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.1.01
0≤1.21.6
LoF obs/exp: 29 / 42.2Missense obs/exp: 365 / 375.1Syn Z: -0.07

ClinVar Variant Classifications

1650 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

GALC · protein map & ClinVar variants

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

Gene2Phenotype Curations

GALC-related Krabbe disease

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

Krabbe disease

MIM #245200

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Newborn screening for Krabbe disease in New York State: the first eight years' experience.
Orsini JJ et al.·Genet Med
2016
Multifocal motor neuropathy.
Beadon K et al.·Curr Opin Neurol
2018Review
GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.
Senkevich K et al.·Brain
2023Meta-analysis
Neuroglial Pathophysiology of Leukodystrophies.
Verkhratsky A et al.·Adv Neurobiol
2025Review
Expression of individual mutations and haplotypes in the galactocerebrosidase gene identified by the newborn screening program in New York State and in confirmed cases of Krabbe's disease.
Saavedra-Matiz CA et al.·J Neurosci Res
2016Cohort
Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.
Hwang N et al.·Clin Genet
2024Cohort
High Prevalence of GALC Gene Variants in Adults With Neurodegenerative Conditions.
Feo F et al.·Eur J Neurol
2025
Krabbe disease--clinical profile.
Tullu MS et al.·Indian Pediatr
2000
Neuroimmune mechanisms in Krabbe's disease.
Potter GB et al.·J Neurosci Res
2016Review
Quantification profiles of enzyme activity, secretion, and psychosine levels of Krabbe disease galactosylceramidase missense variants.
Peng H et al.·J Biol Chem
2025
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
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08
Krabbe Disease

Gene Transfer Clinical Trial for Krabbe Disease

ACTIVE NOT RECRUITING
NCT04693598Phase PHASE1, PHASE2Forge Biologics, IncStarted 2021-11-05
FBX-101
Krabbe Disease

Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously With HSCT

ACTIVE NOT RECRUITING
NCT05739643Phase PHASE1, PHASE2Forge Biologics, IncStarted 2023-02-03
FBX-101

External Resources

Links to major genomics databases and tools