Summary of GALC
The gene codes for a protein, galactosylceramidase. Mutations are linked to Krabbe disease [R].
The Function of GALC
Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon.
Protein names
Recommended name:
GalactocerebrosidaseAlternative name(s):
GALCERaseGalactocerebroside beta-galactosidase
Galactosylceramidase
Galactosylceramide beta-galactosidase
- RS421262 (GALC) ??
- RS4322600 (GALC) ??
- RS55808324 (GALC) ??
- RS7140285 (GALC) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
Substances That Increase GALC
Substances | Interaction | Organism | Category |
Substances That Decrease GALC
Substances | Interaction | Organism | Category |
Advanced Summary
Krabbe disease More than 70 GALC gene mutations that cause Krabbe disease have been identified. The most common mutation in affected individuals of European ancestry deletes a large segment of the GALC gene (written as 30-kb del). Other mutations insert additional DNA building blocks (base pairs) into the GALC gene, delete a small number of base pairs from the gene, or replace a single base pair with an incorrect base pair. These mutations severely reduce the activity of the galactosylceramidase enzyme. As a result, certain galactolipids such as galactosylceramide and psychosine cannot be broken down and accumulate in cells that make myelin. Research suggests that psychosine accumulation is toxic and damages myelin-producing cells, causing the loss of myelin. Without myelin, nerves in the brain and other parts of the body cannot function properly, leading to the signs and symptoms of Krabbe disease. Some individuals with late-onset Krabbe disease have a particular mutation in one of the two copies of the GALC gene in each cell. This mutation replaces one of the building blocks (amino acids) used to make the galactosylceramidase enzyme. Specifically, the amino acid glycine is replaced with the amino acid aspartic acid at position 270 in the enzyme (written as Gly270Asp or G270D). The second copy of the GALC gene usually has a different mutation, such as the large 30-kb deletion. The Gly270Asp mutation probably allows some activity of the galactosylceramidase enzyme, which delays onset of the disease.
The GALC gene provides instructions for making an enzyme called galactosylceramidase. Through a process called hydrolysis, this enzyme uses water molecules to break down certain fats called galactolipids, which are found primarily in the brain and kidneys. Within cells, galactosylceramidase is found in enzyme-filled sacs called lysosomes where it hydrolyzes specific galactolipids, including galactosylceramide and psychosine. Galactosylceramide is an important component of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Psychosine forms during the production of myelin, and then it breaks down with help of galactosylceramidase. Under normal conditions, tissues contain very little psychosine.
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
---|
Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Detected in urine. Detected in testis, brain and placenta (at protein level). Detected in kidney and liver.
Gene Pathways:
Caution:
It is uncertain whether Met-1 or Met-17 is the initiator.
Molecular Function:
Biological Processes:
- Carbohydrate Metabolic Process
- Galactosylceramide Catabolic Process
- Glycosphingolipid Metabolic Process