AGL Gene (Amylo-Alpha-1,6-Glucosidase, 4-Alpha-Glucanotransferase)
Glycogen Debranching Enzyme: Genetic Variants, Function, and Clinical Significance in Glycogen Storage Disease Type III
Gene Information Card
| Symbol | AGL |
|---|---|
| Full Name | Amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p21.2 |
| NCBI Gene ID | 178 ncbi.nlm.nih.gov/gene/178 |
| Ensembl ID | ENSG00000162688 |
| UniProt ID | P35573 |
| OMIM ID | 610860 |
| HGNC ID | 341 |
| Aliases | GDE, glycogen debranching enzyme |
Description
The AGL gene encodes the glycogen debranching enzyme (GDE), a bifunctional enzyme with amylo-1,6-glucosidase and 4-alpha-glucanotransferase activities. This enzyme is essential for glycogen degradation, cleaving alpha-1,6-glycosidic bonds at branch points. Mutations in AGL cause glycogen storage disease type III (GSD III, Cori disease), characterized by accumulation of abnormal glycogen (limit dextrin) in liver and muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease type III (Cori disease) | Loss-of-function mutations in AGL impair glycogen debranching, leading to accumulation of phosphorylase-limit dextrin in liver, muscle, and heart. Results in hypoglycemia, hepatomegaly, myopathy, and cardiomyopathy. | ClinVar, OMIM |
| Glycogen storage disease type IIIa | Mutations affecting both liver and muscle isoforms (most common form). | ClinVar, OMIM |
| Glycogen storage disease type IIIb | Mutations primarily affecting the liver isoform, sparing muscle. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Skeletal muscle | 8.3 | Medium |
| Heart | 6.1 | Low |
| Kidney | 4.2 | Low |
| Brain | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| RH-30 (muscle) | 9.7 | Medium expression |
| K-562 (bone marrow) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2681+1G>A | Splice donor | Common in GSD IIIa | Loss of function |
| c.4456delT | Frameshift | Reported in GSD IIIb | Loss of function |
| p.Arg864* | Nonsense | Found in multiple populations | Loss of function |
| c.1735+1G>T | Splice donor | Associated with severe phenotype | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most AGL mutations are loss-of-function, leading to deficient glycogen debranching enzyme activity and accumulation of limit dextrin.
Gain of Function (GOF)
No gain-of-function mutations reported for AGL.
Dominant Negative (DN)
No dominant-negative mutations reported; GSD III is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • 6-glucosidase activity (GO:0004133) | • 4-alpha-glucanotransferase activity (GO:0004134) |
| • Glycogen debranching enzyme activity (GO:0004135) | • Glycogen catabolic process (GO:0005981) |
| • Cytoplasm (GO:0005737) |
Pathways
• Glycogen degradation (Reactome: R-HSA-71387)
• Metabolism of carbohydrates (Reactome: R-HSA-71387)
Protein Summary
The AGL protein (UniProt P35573) is a 1532-amino acid bifunctional enzyme that catalyzes two sequential reactions in glycogen degradation: (1) 4-alpha-glucanotransferase activity transfers a maltotriosyl unit from a branch to a nearby chain, and (2) amylo-1,6-glucosidase activity hydrolyzes the alpha-1,6-glycosidic bond at the branch point. The enzyme is expressed as multiple isoforms due to alternative splicing, with tissue-specific variants in liver and muscle. Deficiency leads to glycogen storage disease type III.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AGL Knockout HEK293 Cell Line | EDJ-KQ3362 | Human | 178 | Details Get a Quote |
| AGL Knockout A-549 Cell Line | EDJ-KQ26367 | Human | 178 | Details Get a Quote |
| AGL Knockout HCT 116 Cell Line | EDJ-KQ26369 | Human | 178 | Details Get a Quote |
| AGL Knockout HeLa Cell Line | EDJ-KQ26370 | Human | 178 | Details Get a Quote |
