PGAM2

Chr 7AR

phosphoglycerate mutase 2

Also known as: GSD10, PGAM-M, PGAMM

NCBI Gene: 5224ENSG00000164708UniProt: P15259

Phosphoglycerate mutase (PGAM) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. The PGAM is a dimeric enzyme containing, in different tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). This gene encodes muscle-specific PGAM subunit. Mutations in this gene cause muscle phosphoglycerate mutase eficiency, also known as glycogen storage disease X. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Glycogen storage disease XMIM #261670
AR
230
ClinVar variants
36
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PGAM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 112 VUS of 230 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.77LOEUF
pLI 0.000
Z-score -0.29
OE 1.10 (0.68–1.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.67Z-score
OE missense 1.15 (1.02–1.30)
180 obs / 156.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.10 (0.68–1.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.02–1.30)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 10 / 9.1Missense obs/exp: 180 / 156.5Syn Z: -0.65

ClinVar Variant Classifications

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic5
VUS112
Likely Benign62
Benign7
Conflicting13
31
Pathogenic
5
Likely Pathogenic
112
VUS
62
Likely Benign
7
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
28
0
31
Likely Pathogenic
2
1
2
0
5
VUS
0
98
13
1
112
Likely Benign
0
0
19
43
62
Benign
0
1
4
2
7
Conflicting
—13
Total51006646230

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PGAM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycogen storage disease X

MIM #261670

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Muscle phosphoglycerate mutase deficiency revisited.
Naini A et al.·Arch Neurol
2009Case report
Targeted exome sequencing identified a novel frameshift variant in the PGAM2 gene causing glycogen storage disease type X.
Nayab A et al.·Eur J Med Genet
2021Case report
Genetic defects are common in myopathies with tubular aggregates.
Gang Q et al.·Ann Clin Transl Neurol
2022
Natural human knockouts and Mendelian disorders: deep phenotyping in Italian isolates.
Spedicati B et al.·Eur J Hum Genet
2021
Novel significant stage-specific differentially expressed genes in hepatocellular carcinoma.
Sarathi A et al.·BMC Cancer
2019
Clinical and genetic spectrum of glycogen storage disease in Iranian population using targeted gene sequencing.
Beyzaei Z et al.·Sci Rep
2021Case report
Serum p-Cresol and 7-HOCA Levels and Fatty Acid and Purine Metabolism Are Associated with Survival, Progression, and Molecular Classification in GB-Serum Proteome and Metabolome Analysis Pre vs. Post Up-Front Chemoirradiation.
Krauze AV et al.·Curr Oncol
2025
Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin.
Wang J et al.·Genet Med
2013
Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.
Vivante A et al.·Pediatr Nephrol
2017Cohort
Genomic analysis of five chromosome 7p deletion patients with Greig cephalopolysyndactyly syndrome (GCPS).
Schwarzbraun T et al.·Eur J Med Genet
2006Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Hepatocellular carcinoma cells downregulate PGAM2 via SIRT2-mediated deacetylation modification to enhance aerobic glycolysis.
Wang Z et al.·NPJ Precis Oncol
2025🔓 Open Access
Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.
Li Y et al.·Int J Biol Sci
2025🔓 Open Access
Association of single nucleotide polymorphisms in Neuropeptide Y (NPY) and Phosphoglycerate Mutase 2 (PGAM2) genes with growth traits in rabbits.
Helal M et al.·Trop Anim Health Prod
2024🔓 Open Access
Eicosapentaenoic acid-mediated activation of PGAM2 regulates skeletal muscle growth and development via the PI3K/AKT pathway.
Li C et al.·Int J Biol Macromol
2024
Targeting the Metabolic Enzyme PGAM2 Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting BCL2 Signaling.
Li Z et al.·Cancer Res
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools