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…

LOFmechanismARLOEUF 0.972 OMIM phenotypes

Clinical Summary— GBE1

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Gene-Disease Validity (ClinGen)

glycogen storage disease due to glycogen branching enzyme deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

235 unique Pathogenic / Likely Pathogenic· 303 VUS of 1156 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GBE1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.69

OE 0.69 (0.50–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.09Z-score

OE missense 0.99 (0.90–1.08)

352 obs / 356.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.50–0.97)

0≤0.351.4

Missense OE?0.99 (0.90–1.08)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 24 / 34.7Missense obs/exp: 352 / 356.9Syn Z: 0.73

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGBE1-related glycogen storage disease IVLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6843th %ile

GOF

0.5562th %ile

LOF

0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84

Likely Pathogenic151

VUS303

Likely Benign513

Benign36

Conflicting55

Pathogenic

151

Likely Pathogenic

303

VUS

513

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	52	1	31	0	84
Likely Pathogenic	109	30	11	1	151
VUS	1	254	36	12	303
Likely Benign	0	8	216	289	513
Benign	0	4	29	3	36
Conflicting	—				55
Total	162	297	323	305	1,142

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap GBE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →