This report describes a potential model of glycogen storage disease III (GSD3); GSD3 exhibits autosomal recessive inheritance. The gene implicated in this disease is AGL, which is involved in the degradation of glycogen. There is a single orthologous gene in Drosophila, CG9485 for which an amorphic allele created by targeted recombination, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human AGL gene has not been introduced into flies.
A human disease model report has been created for this potential model because variants analogous to disease-implicated mutations in the human AGL gene have been introduced into Dmel\CG9485 by homologous recombination; however, they have not yet been characterized. Variant(s) implicated in human disease introduced (as analogous mutation in fly gene): C1604R in the fly CG9485 gene (corresponds to C1515R in the human AGL gene); W1195stop in the fly CG9485 gene (corresponds to W1099stop in the human AGL gene).
[updated Nov. 2019 by FlyBase; FBrf0222196]
[GLYCOGEN STORAGE DISEASE III; GSD3](https://omim.org/entry/232400)
[AMYLO-1,6-GLUCOSIDASE, 4-ALPHA-GLUCANOTRANSFERASE; AGL](https://omim.org/entry/610860)
Clinically, patients with GSD III present in infancy or early childhood with hepatomegaly, hypoglycemia, and growth retardation. Muscle weakness in those with IIIa is minimal in childhood but can become more severe in adults; some patients develop cardiomyopathy (Shen et al., 1996, pubmed:8755644). [from MIM:232400; 2019.11.02]
Glycogen storage disease type III is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa is the most common subtype, present in about 85% of affected individuals; it manifests with liver and muscle involvement. GSD IIIb, with liver involvement only, comprises about 15% of all GSD III. [Gene Reviews, Glycogen Storage Disease Type III; 2019.11.02]
Glycogen storage disease III (GSD3) is caused by homozygous or compound heterozygous mutation in the AGL gene, which encodes the glycogen debrancher enzyme. [from MIM:232400; 2019.11.02]
AGL encodes the multifunctional glycogen debrancher enzyme which is involved in glycogen degradation. Alternatively spliced transcripts encoding different isoforms have been described; tissue-specific alternative splicing may occur. [Gene Cards, AGL; 2019.11.02]
The AGL gene encodes the glycogen debrancher enzyme, a large monomeric protein with a molecular mass of approximately 160 kD. The enzyme has 2 catalytic activities: amylo-1,6-glucosidase (EC 3.2.1.33) and 4-alpha-glucanotransferase (EC 2.4.1.25). The 2 activities are determined at separate catalytic sites on the polypeptide chain and can function independently of each other. Both activities and glycogen binding are required for complete function (Shen et al., 1996, pubmed:8755644; Endo et al., 2006, pubmed:17047887). [from MIM:232400; 2019.11.02]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human AGL gene (1 Drosophila to 1 human). Dmel\CG9485 shares 47% identity and 63% similarity with the human gene.
