Metabolic myopathy

Summary

Metabolic myopathy (MONDO:0020123) is a disease with 1 cohort gene and 5 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	metabolic myopathy
Mondo ID	MONDO:0020123
Orphanet	98486
NCIT	C98985
SNOMED CT	26111005
UMLS	C0270984
MedGen	452364
GARD	0019472
MedDRA	10068836
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › metabolic myopathy

Related subtypes (31): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, myopathy due to myoadenylate deaminase deficiency, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, myositis disease, collagen 6-related myopathy, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in POMT2, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Subtypes (4): metabolic myopathy due to lactate transporter defect, hereditary myopathy with lactic acidosis due to ISCU deficiency, autosomal dominant mitochondrial myopathy with exercise intolerance, endocrine myopathy

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

1 retrieved; paginated sample, class counts are floors:

1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
92489	NM_000152.5(GAA):c.858+7_858+8insAGCGGGC	GAA	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GAA	Orphanet:308552	Glycogen storage disease due to acid maltase deficiency, infantile onset
GAA	Orphanet:420429	Glycogen storage disease due to acid maltase deficiency, late-onset

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
GAA	HGNC:4065	ENSG00000171298	P10253	Lysosomal alpha-glucosidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GAA	Lysosomal alpha-glucosidase	Essential for the degradation of glycogen in lysosomes.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GAA	Enzyme (other)	yes	3.2.1.20	Glyco_hydro_31_TIM, P_trefoil_dom, Gal_mutarotase_sf_dom

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
granulocyte	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GAA	261	ubiquitous	marker	granulocyte, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GAA	2,116

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GAA	P10253	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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 diseases	1	5710.0×	0.001	GAA
Glycogen storage disease type II (GAA)	1	5710.0×	0.001	GAA
Glycogen metabolism	1	1903.3×	0.002	GAA
Diseases of carbohydrate metabolism	1	815.7×	0.003	GAA
Glycogen breakdown (glycogenolysis)	1	761.3×	0.003	GAA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.017	GAA
Diseases of metabolism	1	80.4×	0.021	GAA
Innate Immune System	1	25.5×	0.058	GAA
Neutrophil degranulation	1	23.1×	0.058	GAA
Disease	1	13.1×	0.084	GAA
Immune System	1	13.0×	0.084	GAA
Metabolism	1	11.6×	0.086	GAA

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
maltose metabolic process	1	16852.0×	3e-04	GAA
sucrose metabolic process	1	16852.0×	3e-04	GAA
obsolete vacuolar sequestering	1	16852.0×	3e-04	GAA
diaphragm contraction	1	4213.0×	0.001	GAA
tissue development	1	1872.4×	0.002	GAA
glycophagy	1	1404.3×	0.002	GAA
glycogen catabolic process	1	1203.7×	0.002	GAA
neuromuscular process controlling posture	1	1053.2×	0.002	GAA
regulation of the force of heart contraction	1	991.3×	0.002	GAA
muscle cell cellular homeostasis	1	648.1×	0.003	GAA
aorta development	1	561.7×	0.003	GAA
cardiac muscle contraction	1	401.2×	0.003	GAA
heart morphogenesis	1	374.5×	0.003	GAA
neuromuscular process controlling balance	1	330.4×	0.004	GAA
lysosome organization	1	306.4×	0.004	GAA
glucose metabolic process	1	255.3×	0.004	GAA
locomotory behavior	1	179.3×	0.006	GAA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GAA	DIENESTROL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GAA	112	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GAA	280	Binding:267, Functional:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GAA	3.2.1.20	alpha-glucosidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GAA	280

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GAA
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02362685	Not specified	RECRUITING	Metabolic Exercise Testing
NCT02745938	Not specified	COMPLETED	GDF-15 as a Biomarker for Mitochondrial Disease
NCT05413681	Not specified	UNKNOWN	Metabolomic Approach During Exercise Testing in Myalgia Induced by eXercise
NCT05456997	Not specified	TERMINATED	Metabolic Myopathy in Endocrinopathy
NCT07268287	Not specified	COMPLETED	Assessment of Energy Metabolism in Metabolic Myopathies