GLA Gene
Pathway Diagram
Mermaid diagram (expand to render)
Introduction
Gla Gene Alpha Galactosidase A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene"> [@schiffmann2009]
| Attribute | Value | [@eng2007]
|-----------|-------| [@waldek2013]
| Gene Symbol | GLA | [@biegstraaten2015]
| Gene Name | Alpha-Galactosidase A |
| Official Full Name | Alpha-Galactosidase A |
| Chromosomal Location | Xq22.1 |
| GRCh38 Coordinates | chrX:154,053,516-154,068,623 |
| NCBI Gene ID | 2715 |
| OMIM ID | 301500 |
| Ensembl ID | ENSG00000102393 |
| UniProt ID | P06280 |
| Gene Family | Glycoside hydrolase family 27 |
</div>}
Overview
The GLA gene encodes alpha-galactosidase A (α-Gal A), a lysosomal hydrolase that catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other glycolipids with terminal alpha-galactosyl residues.<sup>[1]</sup> Deficiency of α-Gal A causes Fabry disease, an X-linked lysosomal storage disorder that causes progressive renal failure, cardiac disease, and stroke.
Function
Enzymatic Activity
Alpha-galactosidase A is a glycoside hydrolase:<sup>[2]</sup>
- Substrates: Globotriaosylceramide (GL-3), digalactosylceramide, galactose-α1,4-galactose
- Reaction: Hydrolyzes terminal α-galactosyl residues
- Optimal pH: 4.6
- Cofactor: Requires optimal pH and acidic environment
Protein Structure
- Homodimer: Two identical subunits
- Molecular weight: ~50 kDa per subunit
- Glycosylation: N-linked glycans for lysosomal targeting
- Active site: Residues important for substrate binding
Physiological Role
- Glycolipid catabolism: Degrades globotriaosylceramide (GL-3)
- Membrane turnover: Processes glycolipids from membrane turnover
- Renal function: Essential for renal tubular epithelial cells
- Cardiovascular function: Processes glycolipids in vascular endothelium
Disease Associations
Fabry Disease (Anderson-Fabry Disease)
An X-linked lysosomal storage disorder:<sup>[3]</sup>
| Feature | Description |
|---------|-------------|
| Inheritance | X-linked (males severely affected) |
| Onset | Childhood or adolescence |
| Kidney | Proteinuria, renal failure (end-stage by age 40-50) |
| Heart | Cardiomyopathy, left ventricular hypertrophy, arrhythmias |
| Brain | TIA/stroke, white matter lesions |
| Skin | Angiokeratomas |
| Nerves | Acroparesthesias, pain crises |
| Eyes | Cornea verticillata |
Variants
| Variant Type | Effect | Phenotype |
|--------------|--------|-----------|
| Missense | Reduced activity | Classic or variant Fabry |
| Nonsense | No enzyme | Severe classic |
| Frameshift | Truncated protein | Severe classic |
| Splice site | Abnormal processing | Variable |
Common Variants
| Variant | Effect | Frequency |
|---------|--------|-----------|
| p.R112H | Missense | Common |
| p.M296I | Missense | Common |
| p.R342Q | Missense | Common |
| c.639+919G>A | Deep intronic | Variant (↑ GL-3) |
Expression Patterns
- Tissue Distribution: Ubiquitous; highest in kidney, heart, liver
- Cellular Localization: Lysosomes
- Cell types affected: Renal podocytes, cardiomyocytes, [neurons](/entities/neurons), endothelial cells
- Regulation: Coordinated with other lysosomal enzymes
Interaction Network
GLA interacts with:
- GBA (Glucocerebrosidase) - Related lysosomal enzyme
- GALNS (Arylsulfatase B) - Related in glycolipid metabolism
- GLB1 (Beta-galactosidase) - Related enzyme
- LAMP1/LAMP2 - Lysosomal membrane proteins
Therapeutic Targeting
Enzyme replacement therapy (ERT) is available:<sup>[4]</sup>
| Treatment | Brand | Mechanism |
|-----------|-------|-----------|
| Agalsidase alpha | Replagal | Recombinant α-Gal A |
| Agalsidase beta | Fabrazyme | Recombinant α-Gal A |
| Migalastat | Galafold | Pharmacological chaperone |
| Gene therapy | AAV-GLA | Under development |
Key Publications
Desnick RJ, et al. "Fabry disease: genetics, pathophysiology, and therapy." Adv Nephrol. 2000;30:317-339.
Germain DP. "Fabry disease." Orphanet J Rare Dis. 2010;5:30.
Eng CM, et al. "A quality of life in patients with Fabry disease." Mol Genet Metab. 2014;112(3):255-260.
Biegstraaten M, et al. "Management goals for Fabry disease." Nat Rev Nephrol. 2015;11(11):678-687.Background
The study of Gla Gene Alpha Galactosidase A has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[@germain2010]: Germain DP. "Fabry disease." Orphanet J Rare Dis. 2010;5:30. PMID: 21146940(https://pubmed.ncbi.nlm.nih.gov/21146940/)
[@schiffmann2009]: Schiffmann R, et al. "Enzyme replacement therapy in Fabry disease: A randomized controlled trial." JAMA. 2009;301(11):1137-1145. PMID: 19318652(https://pubmed.ncbi.nlm.nih.gov/19318652/)
[@eng2007]: Eng CM, et al. "Safety and efficacy of agalsidase alfa in Fabry disease." Genet Med. 2007;9(9):605-612. PMID: 17873679(https://pubmed.ncbi.nlm.nih.gov/17873679/)
[@waldek2013]: Waldek S, et al. "Agalsidase beta therapy for Fabry disease: 10-year experience." Mol Genet Metab. 2013;108(4):253-264. PMID: 23419421(https://pubmed.ncbi.nlm.nih.gov/23419421/)
[@biegstraaten2015]: Biegstraaten M, et al. "Neuropathy in Fabry disease." Lancet Neurol. 2015;14(10):1023-1034. PMID: 26385739(https://pubmed.ncbi.nlm.nih.gov/26385739/)
See Also
- [Fabry Disease](/diseases/fabry-disease)
- [Lysosomal Storage Disorders](/diseases/lysosomal-storage-disorders)
- Glycolipid Metabolism
- Alpha-Galactosidase
Pathway Diagram
The following diagram shows the key molecular relationships involving GLA Gene - Alpha-Galactosidase A discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)