GBE1

Chr 3AR

1,4-alpha-glucan branching enzyme 1

Also known as: APBD, GBE, GSD4

NCBI Gene: 2632 ENSG00000114480 UniProt: Q04446 OMIM: 607839

The encoded glycogen branching enzyme catalyzes the transfer of alpha-1,4-linked glucosyl units to alpha-1,6 positions on glycogen chains, creating branches that increase glycogen solubility and reduce osmotic pressure in cells. Mutations cause glycogen storage disease IV (Andersen disease) and adult-onset polyglucosan body disease through autosomal recessive inheritance. The pathogenic mechanism involves dominant-negative effects of mutant protein.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, Mechanism

The protein encoded by this gene is a glycogen branching enzyme that catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, in reducing the osmotic pressure within cells. Highest level of this enzyme are found in liver and muscle. Mutations in this gene are associated with glycogen storage disease IV (also known as Andersen's disease). [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glycogen storage disease IVMIM #232500

Polyglucosan body disease, adult formMIM #263570

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · glycogen storage disease due to glycogen branching enzyme deficiency · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — GBE1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GBE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

933 rare PASS variants

Rare truncating (LoF)

1 in 970

157 rare PASS variants

Rare synonymous (reference)

1 in 220

308 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GBE1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 84	1 in 950
South Asian	~43k	1 in 53	1 in 960
Remaining (unassigned)	~30k	1 in 52	1 in 590
European (Finnish)	~27k	1 in 170	1 in 500
Admixed American	~22k	1 in 70	1 in 290
African / African American	~21k	1 in 60	1 in 1,000
East Asian	~20k	1 in 110	1 in 1,100
Ashkenazi Jewish	~13k	1 in 250	1 in 1,500
Middle Eastern	~2,883	1 in 42	≈ 1 in 2,500

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 16 coding exons well covered in gnomAD exomes; exons 3, 5, 6, 8, 10 and 3 more marginal. Genomes: all 16.? see exons ↓