GALC (Galactosylceramidase) Gene: Function, Mutations, and Associated Diseases
Comprehensive resource on the GALC gene, its role in sphingolipid metabolism, related disorders like Krabbe disease, and clinical implications.
Gene Information Card
| Symbol | GALC |
|---|---|
| Full Name | galactosylceramidase |
| Gene Type | protein coding |
| Chromosomal Location | 14q31.3 |
| NCBI Gene ID | 2581 ncbi.nlm.nih.gov/gene/2581 |
| Ensembl ID | ENSG00000054983 |
| UniProt ID | P54803 |
| OMIM ID | 606890 |
| HGNC ID | 4115 |
| Aliases | GALCER; GLD; Krabbe disease; galactocerebrosidase |
Description
The GALC gene encodes galactosylceramidase, a lysosomal enzyme that catalyzes the hydrolysis of galactosylceramide and other galactolipids, including psychosine. This enzyme is essential for normal myelin metabolism in the nervous system. Mutations in GALC lead to deficiency of galactosylceramidase, causing accumulation of galactolipids and psychosine, which is toxic to oligodendrocytes and Schwann cells, resulting in demyelination and neurodegeneration. This is the underlying cause of Krabbe disease (globoid cell leukodystrophy), a severe autosomal recessive lysosomal storage disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Krabbe Disease (Globoid Cell Leukodystrophy) | Loss-of-function mutations in GALC lead to deficiency of galactosylceramidase, causing accumulation of psychosine and galactosylceramide, leading to oligodendrocyte death and demyelination. | OMIM #606890; ClinVar |
| Infantile Krabbe Disease | Severe early-onset form due to complete or near-complete loss of GALC enzyme activity, presenting in infancy with irritability, spasticity, and developmental regression. | ClinVar; OMIM |
| Late-Onset Krabbe Disease | Milder form with residual enzyme activity, presenting later in childhood or adulthood with gait disturbances, vision loss, and cognitive decline. | ClinVar; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Liver | 7.1 | Low |
| Lung | 6.3 | Low |
| Spleen | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.5 | High expression |
| HeLa | 9.8 | Medium |
| A549 | 7.2 | Low |
| MCF7 | 6.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.857G>A (p.Gly286Asp) | Missense | Common in infantile Krabbe disease (European) | Loss of enzyme activity |
| c.1905T>C (p.Tyr635Cys) | Missense | Associated with late-onset forms | Partial loss of activity |
| 30-kb deletion (exons 1-10) | Deletion | Found in some populations | Complete loss of function |
| c.1472G>A (p.Trp491Ter) | Nonsense | Rare | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GALC mutations are loss-of-function, leading to reduced or absent galactosylceramidase activity. This results in substrate accumulation and disease.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GALC.
Dominant Negative (DN)
No dominant-negative effects are known; GALC mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • galactosylceramidase activity | • hydrolase activity |
| • lysosome | • sphingolipid metabolic process |
| • galactolipid catabolic process | • myelin maintenance |
Pathways
• Sphingolipid metabolism
• Galactosylceramide degradation
• Lysosomal degradation
Protein Summary
Galactosylceramidase is a lysosomal enzyme composed of 685 amino acids, with a molecular weight of approximately 80 kDa. It is synthesized as a precursor and processed to a mature form. The enzyme requires saposin C as a cofactor for optimal activity. It hydrolyzes galactosylceramide, psychosine, and other galactolipids. Deficiency leads to Krabbe disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GALC Knockout HEK293 Cell Line | EDJ-KQ17876 | Human | 2581 | Details Get a Quote |
| GALC Knockout A-549 Cell Line | EDJ-KQ24083 | Human | 2581 | Details Get a Quote |
| GALC Knockout HeLa Cell Line | EDJ-KQ24084 | Human | 2581 | Details Get a Quote |
| GALC Knockout HCT 116 Cell Line | EDJ-KQ70266 | Human | 2581 | Details Get a Quote |
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