AGL Gene: Glycogen Debranching Enzyme – Function, Mutations, and GSD III

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.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycogen degradation (Reactome: R-HSA-71387)

• Metabolism of carbohydrates (Reactome: R-HSA-71387)

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.