Glycogen storage disease due to muscle beta-enolase deficiency

Summary

Glycogen storage disease due to muscle beta-enolase deficiency (MONDO:0013046) is a disease caused by ENO3 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ENO3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 331

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to muscle beta-enolase deficiency
Mondo ID	MONDO:0013046
MeSH	C567861
OMIM	612932
Orphanet	99849
ICD-11	821809975
UMLS	C2752027
MedGen	442873
GARD	0002125
Is cancer (heuristic)	no

Also known as: glycogen storage disease 13 · glycogen storage disease due to muscle beta-enolase deficiency · glycogen storage disease type 13 · glycogen storage disease XIII · glycogenosis due to muscle beta-enolase deficiency · glycogenosis type 13 · GSD due to muscle beta-enolase deficiency · GSD13 · GSDXIII · muscle enolase deficiency · muscular enolase deficiency

Data availability: 331 ClinVar variants · 4 GenCC gene-disease records.

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 muscle beta-enolase deficiency

Related subtypes (23): glycogen storage disease I, glycogen storage disease due to GLUT2 deficiency, glycogen storage disease II, glycogen storage disease III, glycogen storage disease due to glycogen branching enzyme deficiency, glycogen storage disease V, glycogen storage disease VI, glycogen storage disease VII, glycogen storage disorder due to hepatic glycogen synthase deficiency, Lafora disease, glycogen storage disease due to phosphoglycerate mutase deficiency, lethal congenital glycogen storage disease of heart, Danon disease, glycogen storage disease IXd, glycogen storage disease due to phosphoglycerate kinase 1 deficiency, glycogen storage disease due to muscle and heart glycogen synthase deficiency, glycogen storage disease due to lactate dehydrogenase M-subunit deficiency, polyglucosan body myopathy 1 with or without immunodeficiency, glycogen storage disease due to lactate dehydrogenase deficiency, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, glycogen storage disease due to liver phosphorylase kinase deficiency, GYG1-related disorder of glycogen metabolism, glycogen storage disease IX

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

331 retrieved; paginated sample, class counts are floors:

151 likely benign, 145 uncertain significance, 13 benign, 9 conflicting classifications of pathogenicity, 9 benign/likely benign, 2 pathogenic, 1 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1285634	NM_053013.4(ENO3):c.1070G>A (p.Cys357Tyr)	ENO3	Pathogenic	no assertion criteria provided
916552	NM_053013.4(ENO3):c.1037_1041dup (p.Gly348fs)	ENO3	Pathogenic	criteria provided, single submitter
3068091	NM_053013.4(ENO3):c.1176+2T>C	ENO3	Likely pathogenic	criteria provided, single submitter
16617	NM_053013.4(ENO3):c.467G>A (p.Gly156Asp)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324139	NM_053013.4(ENO3):c.363G>A (p.Ala121=)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324140	NM_053013.4(ENO3):c.417G>A (p.Gly139=)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324150	NM_053013.4(ENO3):c.1047G>A (p.Ser349=)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
388654	NM_053013.4(ENO3):c.249C>T (p.Ser83=)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
422015	NM_053013.4(ENO3):c.710del (p.Pro237fs)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
508315	NM_053013.4(ENO3):c.865+3G>A	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
888830	NM_053013.4(ENO3):c.555C>T (p.Gly185=)	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891096	NM_053013.4(ENO3):c.1235+7C>T	ENO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004098	NM_053013.4(ENO3):c.166C>T (p.Arg56Cys)	ENO3	Uncertain significance	criteria provided, single submitter
1023135	NM_053013.4(ENO3):c.79G>A (p.Ala27Thr)	ENO3	Uncertain significance	criteria provided, single submitter
1040382	NM_053013.4(ENO3):c.772G>A (p.Asp258Asn)	ENO3	Uncertain significance	criteria provided, single submitter
1052640	NM_053013.4(ENO3):c.736G>A (p.Val246Met)	ENO3	Uncertain significance	criteria provided, single submitter
1053761	NM_053013.4(ENO3):c.340G>A (p.Val114Met)	ENO3	Uncertain significance	criteria provided, single submitter
1056492	NM_053013.4(ENO3):c.1093dup (p.Trp365fs)	ENO3	Uncertain significance	criteria provided, single submitter
1285633	NM_053013.4(ENO3):c.559G>A (p.Glu187Lys)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1361398	NM_053013.4(ENO3):c.159C>A (p.Asp53Glu)	ENO3	Uncertain significance	criteria provided, single submitter
1370967	NM_053013.4(ENO3):c.548G>A (p.Arg183His)	ENO3	Uncertain significance	criteria provided, single submitter
1371345	NM_053013.4(ENO3):c.832G>A (p.Glu278Lys)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1382025	NM_053013.4(ENO3):c.806G>A (p.Arg269Gln)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383337	NM_053013.4(ENO3):c.310+1G>C	ENO3	Uncertain significance	criteria provided, single submitter
1392570	NM_053013.4(ENO3):c.716A>G (p.Lys239Arg)	ENO3	Uncertain significance	criteria provided, single submitter
1408271	NM_053013.4(ENO3):c.908C>T (p.Thr303Ile)	ENO3	Uncertain significance	criteria provided, single submitter
1410891	NM_053013.4(ENO3):c.154G>A (p.Gly52Arg)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1436082	NM_053013.4(ENO3):c.737T>C (p.Val246Ala)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1438524	NM_053013.4(ENO3):c.639C>A (p.Phe213Leu)	ENO3	Uncertain significance	criteria provided, single submitter
1440146	NM_053013.4(ENO3):c.760A>C (p.Asn254His)	ENO3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ENO3	Strong	Autosomal recessive	glycogen storage disease due to muscle beta-enolase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ENO3	Orphanet:99849	Glycogen storage disease due to muscle beta-enolase deficiency

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
ENO3	HGNC:3354	ENSG00000108515	P13929	Beta-enolase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ENO3	Beta-enolase	Enolase that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis and the reverse reaction in gluconeogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ENO3	Other/Unknown	no		Enolase, Enolase_CS, Enolase_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
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ENO3	203	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ENO3	4,630

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ENO3	P13929	1

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
Gluconeogenesis	1	439.2×	0.004	ENO3
Glycolysis	1	285.5×	0.004	ENO3

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
canonical glycolysis	1	702.2×	0.003	ENO3
glycolytic process	1	383.0×	0.003	ENO3
gluconeogenesis	1	324.1×	0.003	ENO3

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
ENO3	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ENO3

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)
ENO3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.