Glycogen storage disease due to phosphoglycerate mutase deficiency

Summary

Glycogen storage disease due to phosphoglycerate mutase deficiency (MONDO:0009865) is a disease caused by PGAM2 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PGAM2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 159
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		24	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to phosphoglycerate mutase deficiency
Mondo ID	MONDO:0009865
MeSH	C536176
OMIM	261670
Orphanet	97234
NCIT	C131647
SNOMED CT	61772003
UMLS	C0268149
MedGen	120613
GARD	0009964
Is cancer (heuristic)	no

Also known as: glycogen storage disease caused by mutation in PGAM2 · glycogen storage disease type 10 · glycogen storage disease X · glycogenosis due to phosphoglycerate mutase deficiency · GSD due to phosphoglycerate mutase deficiency · GSD type 10 · GSD10 · GSDX · muscle phosphoglycerate mutase deficiency · myopathy due to phosphoglycerate mutase deficiency · PGAM deficiency · PGAM2 glycogen storage disease · Phosphoglycerate mutase deficiency

Data availability: 159 ClinVar variants · 3 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 phosphoglycerate mutase 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, 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

159 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 51 likely benign, 13 conflicting classifications of pathogenicity, 9 pathogenic, 3 benign, 3 benign/likely benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2030700	NM_000290.4(PGAM2):c.160del (p.Ile54fs)	DBNL	Pathogenic	criteria provided, single submitter
2136502	NM_000290.4(PGAM2):c.538C>T (p.Arg180Ter)	DBNL	Pathogenic	criteria provided, single submitter
2792686	NM_000290.4(PGAM2):c.173C>G (p.Ser58Ter)	DBNL	Pathogenic	criteria provided, single submitter
3616403	NM_000290.4(PGAM2):c.211del (p.Leu71fs)	DBNL	Pathogenic	criteria provided, single submitter
3633329	NM_000290.4(PGAM2):c.74G>A (p.Trp25Ter)	DBNL	Pathogenic	criteria provided, single submitter
418	NM_000290.4(PGAM2):c.233G>A (p.Trp78Ter)	DBNL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4805042	NM_000290.4(PGAM2):c.163del (p.Cys55fs)	DBNL	Pathogenic	criteria provided, single submitter
587530	NM_000290.4(PGAM2):c.533del (p.Gly178fs)	DBNL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073237	NM_000290.4(PGAM2):c.331C>T (p.Gln111Ter)	PGAM2	Pathogenic	criteria provided, single submitter
2055208	NM_000290.4(PGAM2):c.234G>A (p.Trp78Ter)	PGAM2	Pathogenic	criteria provided, single submitter
2422820	NC_000007.13:g.(?44102363)(44105128_?)del	PGAM2	Pathogenic	criteria provided, single submitter
426405	NM_000290.4(PGAM2):c.20del (p.Val7fs)	PGAM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
360270	NM_000290.4(PGAM2):c.726C>T (p.Ala242=)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360272	NM_000290.4(PGAM2):c.459C>T (p.Cys153=)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
387470	NM_000290.4(PGAM2):c.288A>G (p.Thr96=)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
419	NM_000290.4(PGAM2):c.266A>C (p.Glu89Ala)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
421	NM_000290.4(PGAM2):c.290G>A (p.Gly97Asp)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432232	NM_000290.4(PGAM2):c.511A>G (p.Ile171Val)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
440991	NM_000290.4(PGAM2):c.707A>C (p.Glu236Ala)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908403	NM_000290.4(PGAM2):c.252T>C (p.Thr84=)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911381	NM_000290.4(PGAM2):c.480T>C (p.Ile160=)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911382	NM_000290.4(PGAM2):c.455C>T (p.Thr152Ile)	DBNL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289850	NM_000290.4(PGAM2):c.310G>A (p.Ala104Thr)	PGAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
513506	NM_000290.4(PGAM2):c.415-3C>T	PGAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
529224	NM_000290.4(PGAM2):c.119G>A (p.Arg40Gln)	PGAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004776	NM_000290.4(PGAM2):c.19G>A (p.Val7Met)	DBNL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1015223	NM_000290.4(PGAM2):c.719G>A (p.Arg240Gln)	DBNL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1058779	NM_000290.4(PGAM2):c.545T>C (p.Leu182Pro)	DBNL	Uncertain significance	criteria provided, single submitter
1059765	NM_000290.4(PGAM2):c.414+6C>T	DBNL	Uncertain significance	criteria provided, single submitter
1060608	NM_000290.4(PGAM2):c.755C>A (p.Ala252Asp)	DBNL	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
PGAM2	Strong	Autosomal recessive	glycogen storage disease due to phosphoglycerate mutase deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PGAM2	Orphanet:97234	Glycogen storage disease due to phosphoglycerate mutase deficiency

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
PGAM2	HGNC:8889	ENSG00000164708	P15259	Phosphoglycerate mutase 2	gencc,clinvar
DBNL	HGNC:2696	ENSG00000136279	Q9UJU6	Drebrin-like protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PGAM2	Phosphoglycerate mutase 2	Catalyzes the interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction.
DBNL	Drebrin-like protein	Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	8.6×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PGAM2	Enzyme (other)	yes	5.4.2.11	PG/BPGM_mutase_AS, Phosphogly_mut1, His_Pase_superF_clade-1
DBNL	Scaffold/PPI	no		SH3_domain, ADF-H, ADF-H/Gelsolin-like_dom_sf

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
apex of heart	1
hindlimb stylopod muscle	1
right atrium auricular region	1
leukocyte	1
lower esophagus mucosa	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PGAM2	195	broad	yes	apex of heart, hindlimb stylopod muscle, right atrium auricular region
DBNL	230	ubiquitous	marker	lower esophagus mucosa, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PGAM2	2,255
DBNL	347

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DBNL	Q9UJU6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PGAM2	P15259	94.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Caspase-mediated cleavage of cytoskeletal proteins	1	475.8×	0.011	DBNL
Gluconeogenesis	1	219.6×	0.011	PGAM2
Glycolysis	1	142.8×	0.012	PGAM2
Neurexins and neuroligins	1	98.5×	0.013	DBNL
Neutrophil degranulation	1	11.5×	0.085	DBNL

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to mercury ion	1	1203.7×	0.007	PGAM2
podosome assembly	1	1053.2×	0.007	DBNL
striated muscle contraction	1	421.3×	0.009	PGAM2
canonical glycolysis	1	351.1×	0.009	PGAM2
Rac protein signal transduction	1	280.9×	0.009	DBNL
membrane organization	1	255.3×	0.009	DBNL
glycolytic process	1	191.5×	0.010	PGAM2
gluconeogenesis	1	162.0×	0.011	PGAM2
neuron projection morphogenesis	1	138.1×	0.011	DBNL
synapse assembly	1	115.4×	0.012	DBNL
Notch signaling pathway	1	70.8×	0.018	PGAM2
endocytosis	1	47.6×	0.024	DBNL
adaptive immune response	1	42.1×	0.025	DBNL
spermatogenesis	1	17.6×	0.056	PGAM2

Therapeutics

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
PGAM2	0	0
DBNL	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
DBNL	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PGAM2	5.4.2.11	phosphoglycerate mutase (2,3-diphosphoglycerate-dependent)

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	0
D	Druggable family + AlphaFold only, no drug	1	PGAM2
E	Difficult family or no structure, no drug	1	DBNL

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)
PGAM2	0	—
DBNL	1	—

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
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy