Polyglucosan body myopathy type 2

Summary

Polyglucosan body myopathy type 2 (MONDO:0014526) is a disease caused by GYG1 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: GYG1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 256
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	polyglucosan body myopathy type 2
Mondo ID	MONDO:0014526
OMIM	616199
Orphanet	456369
UMLS	C4015452
MedGen	863889
GARD	0017793
Is cancer (heuristic)	no

Also known as: GYG1 polyglucosan body myopathy · PGBM2 · polyglucosan body myopathy 2 · polyglucosan body myopathy caused by mutation in GYG1 · polyglucosan body myopathy type 2

Data availability: 256 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › polyglucosan body myopathy › polyglucosan body myopathy type 2

Related subtypes (1): polyglucosan body myopathy 1 with or without immunodeficiency

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

256 retrieved; paginated sample, class counts are floors:

103 likely benign, 97 uncertain significance, 25 pathogenic, 9 likely pathogenic, 9 benign, 5 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1459543	NC_000003.11:g.(?148447967)(151176497_?)del	COMMD2	Pathogenic	criteria provided, single submitter
162661	NM_004130.4(GYG1):c.143+3G>C	GYG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162662	NM_004130.4(GYG1):c.970C>T (p.Arg324Ter)	GYG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162663	NM_004130.4(GYG1):c.304G>C (p.Asp102His)	GYG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162664	NM_004130.4(GYG1):c.749G>A (p.Trp250Ter)	GYG1	Pathogenic	no assertion criteria provided
162665	NM_004130.4(GYG1):c.487del (p.Asp163fs)	GYG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1879594	NM_004130.4(GYG1):c.646C>T (p.Arg216Ter)	GYG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1906288	NM_004130.4(GYG1):c.683del (p.Thr228fs)	GYG1	Pathogenic	criteria provided, single submitter
1946636	NM_004130.4(GYG1):c.10C>T (p.Gln4Ter)	GYG1	Pathogenic	criteria provided, single submitter
2007595	NM_004130.4(GYG1):c.844dup (p.Tyr282fs)	GYG1	Pathogenic	criteria provided, single submitter
2045936	NM_004130.4(GYG1):c.82C>T (p.Gln28Ter)	GYG1	Pathogenic	criteria provided, single submitter
2048341	NM_004130.4(GYG1):c.352_353del (p.Glu118fs)	GYG1	Pathogenic	criteria provided, single submitter
2081385	NC_000003.12:g.148996742del	GYG1	Pathogenic	criteria provided, single submitter
2926005	NM_004130.4(GYG1):c.26dup (p.Thr10fs)	GYG1	Pathogenic	criteria provided, single submitter
2927980	NM_004130.4(GYG1):c.844_845insG (p.Tyr282Ter)	GYG1	Pathogenic	criteria provided, single submitter
2929759	NM_004130.4(GYG1):c.384G>A (p.Trp128Ter)	GYG1	Pathogenic	criteria provided, single submitter
2949894	NM_004130.4(GYG1):c.93dup (p.Thr32fs)	GYG1	Pathogenic	criteria provided, single submitter
2952434	NM_004130.4(GYG1):c.221T>A (p.Leu74Ter)	GYG1	Pathogenic	criteria provided, single submitter
2953065	NM_004130.4(GYG1):c.490C>T (p.Gln164Ter)	GYG1	Pathogenic	criteria provided, single submitter
3246935	NC_000003.11:g.(?148709428)(148709454_?)del	GYG1	Pathogenic	criteria provided, single submitter
3754301	NM_004130.4(GYG1):c.773dup (p.Leu258fs)	GYG1	Pathogenic	criteria provided, single submitter
3763958	NM_004130.4(GYG1):c.438C>A (p.Tyr146Ter)	GYG1	Pathogenic	criteria provided, single submitter
4784695	NM_004130.4(GYG1):c.561T>G (p.Tyr187Ter)	GYG1	Pathogenic	criteria provided, single submitter
4785162	NM_004130.4(GYG1):c.797_798dup (p.Val267fs)	GYG1	Pathogenic	criteria provided, single submitter
4788300	NM_004130.4(GYG1):c.35del (p.Asn12fs)	GYG1	Pathogenic	criteria provided, single submitter
569450	NM_004130.4(GYG1):c.154G>T (p.Glu52Ter)	GYG1	Pathogenic	criteria provided, single submitter
850059	NM_004130.4(GYG1):c.819T>A (p.Tyr273Ter)	GYG1	Pathogenic	criteria provided, single submitter
855451	NM_004130.4(GYG1):c.631del (p.Val211fs)	GYG1	Pathogenic	criteria provided, single submitter
871315	NM_004130.4(GYG1):c.832dup (p.Ser278fs)	GYG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1477393	NM_004130.4(GYG1):c.3G>C (p.Met1Ile)	GYG1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
GYG1	Definitive	Autosomal recessive	polyglucosan body myopathy type 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GYG1	Orphanet:263297	Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency
GYG1	Orphanet:456369	Polyglucosan body myopathy type 2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GYG1	HGNC:4699	ENSG00000163754	P46976	Glycogenin-1	gencc,clinvar
COMMD2	HGNC:24993	ENSG00000114744	Q86X83	COMM domain-containing protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GYG1	Glycogenin-1	Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme.
COMMD2	COMM domain-containing protein 2	Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex.

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GYG1	Enzyme (other)	yes	2.4.1.186	Glyco_trans_8, Nucleotide-diphossugar_trans, GNT1/Glycosyltrans_8
COMMD2	Other/Unknown	no		COMM, Commd2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
biceps brachii	1
deltoid	1
gluteal muscle	1
cortical plate	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GYG1	304	ubiquitous	marker	biceps brachii, deltoid, gluteal muscle
COMMD2	255	ubiquitous	marker	secondary oocyte, oocyte, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GYG1	1,300
COMMD2	1,298

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GYG1	P46976	23
COMMD2	Q86X83	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 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 XV (GYG1)	1	2855.0×	9e-04	GYG1
Glycogen storage disease type 0 (muscle GYS1)	1	2855.0×	9e-04	GYG1
Glycogen storage disease type II (GAA)	1	2855.0×	9e-04	GYG1
Myoclonic epilepsy of Lafora	1	634.4×	0.003	GYG1
Glycogen synthesis	1	407.9×	0.004	GYG1
Glycogen breakdown (glycogenolysis)	1	380.7×	0.004	GYG1
Neddylation	1	23.7×	0.048	COMMD2
Neutrophil degranulation	1	11.5×	0.085	GYG1

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
obsolete glycogen biosynthetic process via UDP-glucose	1	16852.0×	1e-04	GYG1
glycogen biosynthetic process	1	936.2×	0.001	GYG1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
GYG1	0	0
COMMD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GYG1	2.4.1.186	glycogenin glucosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	GYG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COMMD2

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)
GYG1	0	—
COMMD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study