glycogen storage disease VII

Summary

glycogen storage disease VII (MONDO:0009295) is a disease caused by PFKM (GenCC Definitive), with 2 cohort genes and 4 clinical trials. Top therapeutic interventions include triheptanoin.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PFKM (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 958
• Phenotypes (HPO): 6
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0001903	Anemia	Very frequent (80-99%)
HP:0002486	Myotonia	Very frequent (80-99%)
HP:0009051	Increased muscle glycogen content	Very frequent (80-99%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0002149	Hyperuricemia	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease VII
Mondo ID	MONDO:0009295
MeSH	D006014
OMIM	232800
Orphanet	371
DOID	DOID:11721
NCIT	C118437
SNOMED CT	89597008
UMLS	C0017926
MedGen	5342
GARD	0005686
MedDRA	10053241
NORD	1196
Is cancer (heuristic)	no

Also known as: glycogen storage disease caused by mutation in PFKM · Glycogen Storage Disease Type 7 · glycogen storage disease type 7 · glycogen storage disease type VII · glycogen storage disease VII · glycogenosis due to muscle phosphofructokinase deficiency · glycogenosis type 7 · glycogenosis type VII · GSD due to muscle phosphofructokinase deficiency · GSD type 7 · GSD type VII · GSD7 · GSDVII · PFKM glycogen storage disease · phosphofructokinase deficiency · Tarui disease

Data availability: 958 ClinVar variants · 5 GenCC gene-disease records · 5 cell lines.

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 VII

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 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 muscle beta-enolase 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

600 retrieved; paginated sample, class counts are floors:

381 likely benign, 103 uncertain significance, 56 likely pathogenic, 23 pathogenic, 17 benign, 14 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068782	NM_000289.6(PFKM):c.1607del (p.Gly535_Ser536insTer)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074467	NM_000289.6(PFKM):c.165T>A (p.Tyr55Ter)	PFKM	Pathogenic	criteria provided, single submitter
1074469	NM_000289.6(PFKM):c.1413-64A>G	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1152	NM_000289.6(PFKM):c.1341+1G>T	PFKM	Pathogenic	no assertion criteria provided
1153	NM_000289.6(PFKM):c.428-2A>C	PFKM	Pathogenic	no assertion criteria provided
1154	NM_000289.6(PFKM):c.116G>C (p.Arg39Pro)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1157	NM_000289.6(PFKM):c.116G>T (p.Arg39Leu)	PFKM	Pathogenic	no assertion criteria provided
1158	NM_000289.6(PFKM):c.283C>T (p.Arg95Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1159	NM_000289.6(PFKM):c.2058G>T (p.Trp686Cys)	PFKM	Pathogenic	no assertion criteria provided
1371672	NM_000289.6(PFKM):c.381_385dup (p.Arg129fs)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381155	NM_000289.6(PFKM):c.646dup (p.Ala216fs)	PFKM	Pathogenic	criteria provided, single submitter
1398900	NM_000289.6(PFKM):c.74del (p.Gly25fs)	PFKM	Pathogenic	criteria provided, single submitter
1402514	NM_000289.6(PFKM):c.1294C>T (p.Arg432Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1422945	NM_000289.6(PFKM):c.1761del (p.Ala588fs)	PFKM	Pathogenic	criteria provided, single submitter
1429205	NM_000289.6(PFKM):c.1704del (p.Phe568fs)	PFKM	Pathogenic	criteria provided, single submitter
1429839	NM_000289.6(PFKM):c.736C>T (p.Arg246Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453463	NM_000289.6(PFKM):c.237+1G>C	PFKM	Pathogenic	criteria provided, single submitter
1453757	NM_000289.6(PFKM):c.1338del (p.Gln447fs)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455763	NM_000289.6(PFKM):c.2075_2076del (p.Lys692fs)	PFKM	Pathogenic	criteria provided, single submitter
1456055	NM_000289.6(PFKM):c.2080_2081del (p.Ser694fs)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457501	NM_000289.6(PFKM):c.874del (p.Arg292fs)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1725612	NM_000289.6(PFKM):c.1321G>T (p.Glu441Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189239	NM_000289.6(PFKM):c.237+1G>A	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2004770	NM_000289.6(PFKM):c.21dup (p.Ala8fs)	PFKM	Pathogenic	criteria provided, single submitter
2016699	NM_000289.6(PFKM):c.1057C>T (p.Gln353Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2018449	NM_000289.6(PFKM):c.1053del (p.Cys351fs)	PFKM	Pathogenic	criteria provided, single submitter
2030770	NM_000289.6(PFKM):c.1828_1834del (p.Glu610fs)	PFKM	Pathogenic	criteria provided, single submitter
2125307	NM_000289.6(PFKM):c.290del (p.Gly97fs)	PFKM	Pathogenic	criteria provided, single submitter
2196187	NM_000289.6(PFKM):c.1807C>T (p.Arg603Ter)	PFKM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2413895	NM_000289.6(PFKM):c.780_783del (p.Ile260fs)	PFKM	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PFKM	Definitive	Autosomal recessive	glycogen storage disease VII	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PFKM	Orphanet:371	Glycogen storage disease due to muscle phosphofructokinase deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PFKM	HGNC:8877	ENSG00000152556	P08237	ATP-dependent 6-phosphofructokinase, muscle type	gencc,clinvar
MIR6505	HGNC:50104	ENSG00000275770		microRNA 6505	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PFKM	ATP-dependent 6-phosphofructokinase, muscle type	Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PFKM	Kinase	yes	2.7.1.11	Phosphofructokinase_dom, 6-Pfructokinase_euk, Phosphofructokinase_CS
MIR6505	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gluteal muscle	1
skeletal muscle tissue of rectus abdominis	1
triceps brachii	1
adrenal tissue	1
skeletal muscle tissue	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PFKM	302	ubiquitous	marker	gluteal muscle, triceps brachii, skeletal muscle tissue of rectus abdominis
MIR6505	98		yes	skeletal muscle tissue, adrenal tissue, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PFKM	3,710
MIR6505	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PFKM	P08237	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Glycolysis	1	285.5×	0.004	PFKM

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
glycolytic process through fructose-6-phosphate	1	16852.0×	3e-04	PFKM
glycolysis from storage polysaccharide through glucose-1-phosphate	1	16852.0×	3e-04	PFKM
fructose 1,6-bisphosphate metabolic process	1	2106.5×	0.002	PFKM
glycogen catabolic process	1	1203.7×	0.002	PFKM
fructose 6-phosphate metabolic process	1	1123.5×	0.002	PFKM
canonical glycolysis	1	702.2×	0.002	PFKM
muscle cell cellular homeostasis	1	648.1×	0.002	PFKM
glycolytic process	1	383.0×	0.004	PFKM
positive regulation of insulin secretion	1	255.3×	0.005	PFKM
glucose homeostasis	1	130.6×	0.008	PFKM
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	PFKM

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Triheptanoin.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PFKM	0	0
MIR6505	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PFKM	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PFKM	2.7.1.11	6-phosphofructokinase

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	PFKM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MIR6505

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PFKM	2	—
MIR6505	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03642860	PHASE2	COMPLETED	The Effect of Triheptanoin on Fatty Acid Oxidation and Exercise Tolerance in Patients With Glycogenoses
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study
NCT00001331	Not specified	COMPLETED	Genetic and Family Studies of Inherited Muscle Diseases
NCT02385162	Not specified	WITHDRAWN	Biomarker for Glycogen Storage Diseases (BioGlycogen)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRIHEPTANOIN	4	1