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AGL

amylo-alpha-1,6-glucosidase and 4-alpha-glucanotransferase

The AGL gene provides instructions for producing the glycogen debranching enzyme, which is crucial for breaking down glycogen, the body's stored form of glucose. The AGL gene encodes the glycogen debranching enzyme, an essential component of carbohydrate metabolism.

Chromosome 1p21.2 Autosomal recessive HGNC:321 Tier C
AGL 1p21.2 p arm q arm 1

AGL is located on the short (p) arm of chromosome 1, at band 1p21.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

Carrier Screening panel
AGL is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
AGL is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The AGL gene, also known as amylo-alpha-1,6-glucosidase and 4-alpha-glucanotransferase, is integral to the body's energy regulation system. It provides the genetic blueprint for the glycogen debranching enzyme, which plays a pivotal role in the breakdown of glycogen.

Glycogen serves as the primary storage form of glucose, a simple sugar essential for cellular energy. The proper functioning of the AGL gene is therefore vital for maintaining normal metabolic processes and ensuring a steady supply of energy throughout the body.

What the gene does

The glycogen debranching enzyme, encoded by the AGL gene, is responsible for processing glycogen, a complex carbohydrate made up of numerous glucose units. Glycogen has a branched structure, allowing for efficient storage and rapid mobilisation of glucose when needed for fuel. The AGL enzyme specifically targets the side chains of glycogen molecules.

Without this enzyme, these branches cannot be effectively broken down, leading to an accumulation of abnormal glycogen structures within cells. The AGL gene produces various forms, or isoforms, of this enzyme, which differ in size and are active in distinct tissues, highlighting its broad importance in energy metabolism.

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Chromosome location

The AGL gene is situated on chromosome 1, specifically at band 1p21.2. This genomic location is where the gene's DNA sequence resides, providing the instructions for synthesising the glycogen debranching enzyme.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants within the AGL gene can impact the production or function of the glycogen debranching enzyme. These genetic changes can range from single nucleotide alterations to larger structural variations, potentially affecting the enzyme's ability to break down glycogen effectively. Such variants are typically inherited in an autosomal recessive manner.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for AGL.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1107del
Deletion
 p.Glu369fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease type III
c.1177C>T
single nucleotide variant
 p.Gln393Ter Pathogenic ★★☆☆ AGL-related disorder
c.1183C>T
single nucleotide variant
 p.Gln395Ter Pathogenic ★★☆☆ Glycogen storage disease type III
c.1735+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease type III
c.1777del
Deletion
 p.Val593fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease type III
c.1999C>T
single nucleotide variant
 p.Gln667Ter Pathogenic ★★☆☆ Glycogen storage disease type III
c.2125del
Deletion
 p.His709fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease type III
c.2214del
Deletion
 p.Ser738fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease type III
c.34del
Deletion
 p.Leu11_Leu12insTer Pathogenic ★★☆☆ Glycogen storage disease type III
c.3625C>T
single nucleotide variant
 p.Gln1209Ter Pathogenic ★★☆☆ Glycogen storage disease type III

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the AGL gene are primarily associated with inherited metabolic disorders, including Glycogen Storage Disease Type III and Debrancher deficiency (GSD IIIa). These conditions arise when the glycogen debranching enzyme is deficient or non-functional, leading to the abnormal accumulation of glycogen in various tissues, such as the liver and muscles.

Inheritance pattern

Conditions caused by pathogenic AGL variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous AGL carrier status across ancestry groups?

UK clinical status

The AGL gene is recognised within the UK's NHS Genomic Medicine Service, featuring on several NHS England national genomic test directories. It is listed as 'green' for conditions such as Acute rhabdomyolysis, DDG2P, Foetal anomalies, Glycogen storage disease (R274), Ketotic hypoglycaemia, Likely inborn error of metabolism (R98), Rhabdomyolysis and metabolic muscle disorders, and Undiagnosed metabolic disorders, indicating its clinical utility for these panels.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Acute rhabdomyolysis · R419 NHS GMS → Fetal anomalies · R21 NHS GMS → Glycogen storage disease · R274 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → DDG2P NHS GMS → Rhabdomyolysis and metabolic muscle disorders NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the AGL gene?

The AGL gene provides instructions for creating the glycogen debranching enzyme, which is crucial for breaking down glycogen, the body's main stored form of glucose. This process is essential for maintaining energy levels.

How are conditions associated with the AGL gene inherited?

Conditions linked to the AGL gene, such as Glycogen Storage Disease Type III, are typically inherited in an autosomal recessive manner. This means an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.

What happens if the glycogen debranching enzyme doesn't work correctly?

If the glycogen debranching enzyme, encoded by the AGL gene, is non-functional, the branched structure of glycogen cannot be properly broken down. This leads to an accumulation of abnormal glycogen in tissues, causing conditions like Glycogen Storage Disease Type III.

References

  1. Cheng A, Zhang M, Okubo M. Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions. Human molecular genetics. 2009. PMID: 19299494
  2. Lucchiari S, Pagliarani S, Salani S. Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. Human mutation. 2006. PMID: 16705713
  3. Endo Y, Horinishi A, Vorgerd M. Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey. Journal of human genetics. 2006. PMID: 17047887
  4. Frisbie JH, O'Connell DJ, Tow DE. Autologous radioiodinated fibrinogen, simplified. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1975. PMID: 1194993
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .