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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
AGL
amylo-alpha-1,6-glucosidase and 4-alpha-glucanotransferase
Chromosome 1 Β· 1p21.2
NCBI Gene: 178Ensembl: ENSG00000162688.18HGNC: HGNC:321UniProt: A0A0S2A4E4
111PubMed Papers
21Diseases
0Drugs
627Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
4-alpha-glucanotransferase activityamylo-alpha-1,6-glucosidase activityprotein bindingcytosolglycogen storage disease IIIdisorder of glycogen metabolismGlycogen storage disease due to glycogenin deficiencygenetic disorder
✦AI Summary

AGL (amylo-alpha-1,6-glucosidase and 4-alpha-glucanotransferase) is a multifunctional enzyme that acts as both a 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation 1. The gene spans 85 kb on chromosome 1, containing 35 exons that encode a 7.0-kb mRNA producing 1532 amino acids 1. AGL exhibits tissue-specific expression through at least two promoter regions: the major isoform is widely expressed in liver and muscle, while muscle-specific isoforms are driven by an alternative promoter 1. Genetic deficiency of AGL causes glycogen storage disease type III (GSD-III), a disorder of glycogen metabolism characterized by impaired glycogen breakdown 1. Loss of AGL function in bladder cancer cells impairs normal glycogen metabolism, decreasing cellular glycogen storage and increasing lactate production, while simultaneously elevating serine-to-glycine conversion through SHMT2 upregulation, which promotes nucleotide synthesis and cell proliferation 2. This metabolic reprogramming represents a key mechanism in bladder tumorigenesis. Understanding AGL's critical role in glycogen homeostasis and its dysregulation in disease provides important insights for developing targeted therapeutic strategies for both genetic glycogen storage disorders and metabolic complications in cancer.

Sources cited
1
AGL is a multifunctional enzyme with glycosyltransferase and glucosidase activities in glycogen degradation; gene structure, tissue-specific expression patterns, and GSD-III association
PMID: 8954797
2
Loss of AGL in bladder cancer impairs glycogen metabolism, decreases glycogen storage, and increases lactate production; AGL loss increases SHMT2 activity promoting nucleotide synthesis
PMID: 26975021
⚠Limited data available β€” This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
glycogen storage disease IIIOpen Targets
0.83Strong
disorder of glycogen metabolismOpen Targets
0.77Strong
Glycogen storage disease due to glycogenin deficiencyOpen Targets
0.61Moderate
genetic disorderOpen Targets
0.51Moderate
Acute rhabdomyolysisOpen Targets
0.46Moderate
Abnormality of metabolism/homeostasisOpen Targets
0.34Weak
response to xenobiotic stimulusOpen Targets
0.31Weak
exfoliative dermatitisOpen Targets
0.29Weak
ileostomyOpen Targets
0.27Weak
hypertrophic cardiomyopathyOpen Targets
0.19Weak
Meniere diseaseOpen Targets
0.16Weak
essential tremorOpen Targets
0.09Suggestive
urinary bladder carcinomaOpen Targets
0.08Suggestive
Young adult-onset ParkinsonismOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
movement disorderOpen Targets
0.07Suggestive
Hereditary late-onset Parkinson diseaseOpen Targets
0.07Suggestive
dystonia 27Open Targets
0.07Suggestive
Cranio-cervical dystonia with laryngeal and upper-limb involvementOpen Targets
0.06Suggestive
X-linked dystonia-parkinsonismOpen Targets
0.06Suggestive
Glycogen storage disease 3UniProt
Pathogenic Variants627
NM_000642.3(AGL):c.2590C>T (p.Arg864Ter)Pathogenic
Glycogen storage disease type III|not provided|Acute rhabdomyolysis
β˜…β˜…β˜†β˜†2026β†’ Residue 864
NM_000642.3(AGL):c.4459C>T (p.Arg1487Ter)Pathogenic
Glycogen storage disease type III|Glycogen storage disease
β˜…β˜…β˜†β˜†2026β†’ Residue 1487
NM_000642.3(AGL):c.3444C>A (p.Tyr1148Ter)Pathogenic
Glycogen storage disease type III|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1148
NM_000642.3(AGL):c.808G>T (p.Gly270Ter)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 270
NM_000642.3(AGL):c.3216_3217del (p.Glu1072fs)Pathogenic
not provided|Glycogen storage disease type III|Glycogen storage disease IIIa
β˜…β˜…β˜†β˜†2026β†’ Residue 1072
NM_000642.3(AGL):c.2960G>A (p.Trp987Ter)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 987
NM_000642.3(AGL):c.4260-12A>GPathogenic
Glycogen storage disease IIIb|Glycogen storage disease IIIa|Glycogen storage disease type III|not provided|Glycogen storage disease|AGL-related disorder
β˜…β˜…β˜†β˜†2026
NM_000642.3(AGL):c.2309-1G>APathogenic
Glycogen storage disease type III|Glycogen storage disease IIIa
β˜…β˜…β˜†β˜†2026
NM_000642.3(AGL):c.2949+2T>ALikely pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026
NM_000642.3(AGL):c.2670del (p.Pro891fs)Pathogenic
not provided|Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 891
NM_000642.3(AGL):c.118C>T (p.Gln40Ter)Pathogenic
Glycogen storage disease type III|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 40
NM_000642.3(AGL):c.18_19del (p.Gln6fs)Pathogenic
Glycogen storage disease IIIb|Glycogen storage disease type III|not provided|Glycogen storage disease|AGL-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 6
NM_000642.3(AGL):c.22C>T (p.Arg8Ter)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 8
NM_000642.3(AGL):c.256C>T (p.Gln86Ter)Pathogenic
Glycogen storage disease type III|Glycogen storage disease IIIa|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 86
NM_000642.3(AGL):c.3362+1G>APathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026
NM_000642.3(AGL):c.4525del (p.Gln1509fs)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 1509
NM_000642.3(AGL):c.22del (p.Arg8fs)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2026β†’ Residue 8
NM_000642.3(AGL):c.3554del (p.Thr1185fs)Pathogenic
Glycogen storage disease type III|Glycogen storage disease
β˜…β˜…β˜†β˜†2025β†’ Residue 1185
NM_000642.3(AGL):c.1078C>T (p.His360Tyr)Pathogenic
Glycogen storage disease type III|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 360
NM_000642.3(AGL):c.1002_1005dup (p.Ile336fs)Pathogenic
Glycogen storage disease type III
β˜…β˜…β˜†β˜†2025β†’ Residue 336
View on ClinVar β†—
Related Genes
G6PC1Protein interaction100%UGP2Protein interaction99%NOP53Protein interaction98%AMY2BProtein interaction97%AMY1BProtein interaction97%AMY2AProtein interaction97%
Tissue Expression6 tissues
Heart
100%
Liver
69%
Brain
34%
Bone Marrow
20%
Lung
17%
Ovary
15%
Gene Interaction Network
Click a node to explore
AGLG6PC1UGP2NOP53AMY2BAMY1BAMY2A
PROTEIN STRUCTURE
Preparing viewer…
PDB8ZEQ Β· 3.36 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.72LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.53–0.72]
RankingsWhere AGL stands among ~20K protein-coding genes
  • #4,258of 20,598
    Most Researched111 Β· top quartile
  • #79of 5,498
    Most Pathogenic Variants627 Β· top 5%
  • #5,554of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedAGL
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Metabolic phenotype of bladder cancer.
PMID: 26975021
Cancer Treat Rev Β· 2016
1.00
2
Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects.
PMID: 31527435
Nutrients Β· 2019
0.90
3
Generalized lipoatrophy syndromes.
PMID: 34562560
Presse Med Β· 2021
0.80
4
Non-Antibiotic Antimony-Based Antimicrobials.
PMID: 36363997
Molecules Β· 2022
0.70
5
Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis.
PMID: 38145659
J Control Release Β· 2024
0.60