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GBE1

1,4-alpha-glucan branching enzyme 1

The GBE1 gene encodes the glycogen branching enzyme, which is essential for creating the branched structure of glycogen, a primary form of stored energy in the body. The GBE1 gene provides instructions for producing the glycogen branching enzyme.

Chromosome 3p12.2 Autosomal recessive HGNC:4180 Tier C
GBE1 3p12.2 p arm q arm 3

GBE1 is located on the short (p) arm of chromosome 3, at band 3p12.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 3 in the library →

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Clinical tests that include this

Carrier Screening panel
GBE1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The GBE1 gene is responsible for directing the production of the 1,4-alpha-glucan branching enzyme 1, commonly known as glycogen branching enzyme. This enzyme is critical for the final stages of glycogen synthesis, ensuring the formation of its characteristic branched structure. Glycogen acts as the body's principal stored form of glucose, providing readily available energy.

What the gene does

The glycogen branching enzyme, encoded by the GBE1 gene, catalyses the formation of alpha-1,6-glycosidic bonds during glycogen synthesis. This process creates branches in the glycogen molecule by transferring a segment of an alpha-1,4-linked glucan chain to a C6 hydroxyl group on a glucose residue within another glucan chain. These branches are crucial because they increase the number of non-reducing ends, which in turn allows for more rapid synthesis and breakdown of glycogen when energy is required. A properly branched glycogen structure ensures both compact storage and efficient glucose release, vital for maintaining cellular energy homeostasis.

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Chromosome location

The GBE1 gene is located on chromosome 3, specifically at position 3p12.2. This genomic location indicates its precise address within the human genome, aiding in genetic studies and understanding its role in inherited conditions.

Protein structure

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

Key variants

Variants within the GBE1 gene can lead to alterations in the glycogen branching enzyme's function. These genetic changes can range from single amino acid substitutions to larger deletions or insertions, potentially affecting the enzyme's ability to properly form branched glycogen molecules. The specific impact of a variant often depends on its location and the nature of the change.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for GBE1.
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.1053del
Deletion
 p.Phe351fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.1098_1099insGTGA
Insertion
 p.His367fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.136C>T
single nucleotide variant
 p.Gln46Ter Pathogenic ★★☆☆ Glycogen storage disease, type IV
c.144-1G>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.167del
Deletion
 p.Ile55_Leu56insTer Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease IV, classic hepatic
c.1680C>G
single nucleotide variant
 p.Tyr560Ter Pathogenic ★★☆☆ Glycogen storage disease IV, classic hepatic
c.1823_1824del
Deletion
 p.His608fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.26del
Deletion
 p.Ala9fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.302_303del
Deletion
 p.Thr101fs Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease, type IV
c.691+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Glycogen storage disease IV, classic hepatic

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 GBE1 gene are associated with inherited conditions primarily affecting glycogen metabolism. These include Adult polyglucosan body disease and Glycogen Storage Disease Type IV. These disorders typically arise when the glycogen branching enzyme is deficient or non-functional, leading to the accumulation of abnormal glycogen structures in various tissues.

Inheritance pattern

Conditions caused by pathogenic GBE1 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 GBE1 carrier status across ancestry groups?

UK clinical status

GBE1 is recognised within the UK's NHS Genomic Medicine Service, with its involvement in several clinical panels. It is listed as 'green' for conditions such as Acute rhabdomyolysis, Arthrogryposis, Congenital myopathy, Glycogen storage disease, and Inherited white matter disorders, indicating that genes on these panels are considered to be of high clinical validity.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Acute rhabdomyolysis · R419 NHS GMS → Arthrogryposis · R83 NHS GMS → Congenital myopathy · R81 NHS GMS → Fetal anomalies · R21 NHS GMS → Glycogen storage disease · R274 NHS GMS → Leukodystrophy, adult onset · R62 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → DDG2P 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 glycogen and why is branching important?

Glycogen is a complex carbohydrate that serves as the body's main form of glucose storage, particularly in the liver and muscles. Branching is crucial because it increases the molecule's surface area, allowing for quicker synthesis and breakdown, which is vital for efficient energy release.

What does 'autosomal recessive inheritance' mean for GBE1-related conditions?

Autosomal recessive inheritance means that an individual must inherit two copies of a pathogenic GBE1 variant - one from each parent - to develop the associated condition. Carriers, who have one pathogenic variant and one working copy, typically do not show symptoms but can pass the variant to their children.

What are the main conditions linked to GBE1 variants?

Variants in the GBE1 gene are primarily associated with Glycogen Storage Disease Type IV and Adult polyglucosan body disease. These conditions result from the improper formation or accumulation of glycogen due to a dysfunctional glycogen branching enzyme.

References

  1. Mochel F, Schiffmann R, Steenweg ME. Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings. Annals of neurology. 2012. PMID: 23034915
  2. Massa R, Bruno C, Martorana A. Adult polyglucosan body disease: proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene. Muscle & nerve. 2008. PMID: 17994551
  3. Nolte KW, Janecke AR, Vorgerd M. Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. Acta neuropathologica. 2008. PMID: 18661138
  4. Klein CJ, Boes CJ, Chapin JE. Adult polyglucosan body disease: case description of an expanding genetic and clinical syndrome. Muscle & nerve. 2004. PMID: 14755501
  5. Bruno C, van Diggelen OP, Cassandrini D. Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV). Neurology. 2004. PMID: 15452297
  6. Moses SW, Parvari R. The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies. Current molecular medicine. 2002. PMID: 11949934
  7. Lossos A, Meiner Z, Barash V. Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene. Annals of neurology. 1998. PMID: 9851430
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 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .