GALC

Chr 14AR

galactosylceramidase

NCBI Gene: 2581 ENSG00000054983 UniProt: P54803 OMIM: 606890

The protein encoded by this gene is a lysosomal enzyme that hydrolyzes galactose ester bonds in galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations cause Krabbe disease (globoid cell leukodystrophy) through autosomal recessive inheritance. The pathogenic mechanism involves deficiency of this galactocerebrosidase enzyme leading to accumulation of toxic galactolipid substrates in the nervous system.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.941 OMIM phenotype

Clinical Summary— GALC

🧬

Gene-Disease Validity (ClinGen)

Krabbe disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

53 unique Pathogenic / Likely Pathogenic· 78 VUS of 293 total submissions

💊

Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — GALC

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.88

OE 0.69 (0.51–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.19Z-score

OE missense 0.97 (0.89–1.06)

365 obs / 375.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.51–0.94)

0≤0.351.4

Missense OE?0.97 (0.89–1.06)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 29 / 42.2Missense obs/exp: 365 / 375.1Syn Z: -0.07

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22

Likely Pathogenic31

VUS78

Likely Benign138

Benign2

Conflicting4

Pathogenic

Likely Pathogenic

VUS

138

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	1	7	0	22
Likely Pathogenic	23	6	2	0	31
VUS	1	72	4	1	78
Likely Benign	0	0	88	50	138
Benign	0	0	2	0	2
Conflicting	—				4
Total	38	79	103	51	275

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 6) ClinVar copy-number / structural variants overlap GALC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →