Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form

Summary

Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form (MONDO:0017700) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form
Mondo ID	MONDO:0017700
Orphanet	308698
UMLS	C1856305
MedGen	343524
GARD	0017399
Is cancer (heuristic)	no

Also known as: GBE deficiency, childhood neuromuscular form · glycogen storage disease type 4, childhood neuromuscular form · glycogen storage disease type IV, childhood neuromuscular form · glycogenosis due to glycogen branching enzyme deficiency, childhood neuromuscular form · glycogenosis type 4, childhood neuromuscular form · glycogenosis type IV, childhood neuromuscular form · GSD due to glycogen branching enzyme deficiency, childhood neuromuscular form · GSD type 4, childhood neuromuscular form · GSDIV, childhood neuromuscular form

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease due to glycogen branching enzyme deficiency › glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form

Related subtypes (7): adult polyglucosan body disease, glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form, glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form, glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form, glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form, glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form, glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2781	NM_000158.4(GBE1):c.1570C>T (p.Arg524Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2788	NM_000158.4(GBE1):c.1883A>G (p.His628Arg)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GBE1	Orphanet:206583	Adult polyglucosan body disease
GBE1	Orphanet:308621	Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form
GBE1	Orphanet:308638	Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form
GBE1	Orphanet:308655	Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form
GBE1	Orphanet:308670	Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form
GBE1	Orphanet:308684	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form
GBE1	Orphanet:308698	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form
GBE1	Orphanet:308712	Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GBE1	HGNC:4180	ENSG00000114480	Q04446	1,4-alpha-glucan-branching enzyme	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GBE1	1,4-alpha-glucan-branching enzyme	Glycogen-branching enzyme participates in the glycogen biosynthetic process along with glycogenin and glycogen synthase.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GBE1	Antibody/Immunoglobulin	yes		Glyco_hydro_13_N, GH13_cat_dom, A-amylase/branching_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
gluteal muscle	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GBE1	293	ubiquitous	marker	gluteal muscle, tibialis anterior, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GBE1	3,402

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GBE1	Q04446	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycogen storage disease type IV (GBE1)	1	3806.7×	5e-04	GBE1
Glycogen synthesis	1	815.7×	0.001	GBE1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycogen biosynthetic process	1	936.2×	0.004	GBE1
glycogen metabolic process	1	526.6×	0.004	GBE1
generation of precursor metabolites and energy	1	343.9×	0.004	GBE1
negative regulation of neuron apoptotic process	1	110.9×	0.009	GBE1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GBE1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GBE1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GBE1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.