PGAM1: Phosphoglycerate Mutase 1 – Glycolytic Enzyme and Cancer Target
Comprehensive genomic and proteomic overview of PGAM1, a key enzyme in glycolysis and gluconeogenesis.
Gene Information Card
| Symbol | PGAM1 |
|---|---|
| Full Name | phosphoglycerate mutase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q25.3 |
| NCBI Gene ID | 5223 ncbi.nlm.nih.gov/gene/5223 |
| Ensembl ID | ENSG00000120071 |
| UniProt ID | P18669 |
| OMIM ID | 172250 |
| HGNC ID | 8888 |
| Aliases | PGAMA, PGAM-B, BPG-dependent PGAM 1, phosphoglycerate mutase isozyme B |
Description
PGAM1 (phosphoglycerate mutase 1) encodes a glycolytic enzyme that catalyzes the interconversion of 3-phosphoglycerate and 2-phosphoglycerate in the Embden-Meyerhof pathway. It is a homodimeric protein that requires 2,3-bisphosphoglycerate as a cofactor. PGAM1 is overexpressed in many cancers and plays a role in cell proliferation, metabolism, and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease due to phosphoglycerate mutase deficiency | Loss-of-function mutations in PGAM1 impair glycolysis, leading to exercise intolerance and myopathy. | OMIM #261670 |
| Cancer (various types) | PGAM1 overexpression promotes aerobic glycolysis (Warburg effect) and tumor growth. | COSMIC; PMID: 22956769 |
| Breast cancer | PGAM1 upregulation correlates with poor prognosis and metabolic reprogramming. | ClinVar; PMID: 25944712 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 58.2 | High |
| Heart | 42.1 | High |
| Brain | 18.5 | Medium |
| Liver | 12.3 | Medium |
| Kidney | 15.7 | Medium |
| Lung | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 45.6 | High expression |
| HeLa | 38.2 | High expression |
| MCF7 | 52.1 | High expression |
| A549 | 41.3 | High expression |
| K562 | 22.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.233G>A (p.Arg78His) | Missense | Rare | Reduced enzymatic activity; associated with phosphoglycerate mutase deficiency |
| c.464C>T (p.Thr155Ile) | Missense | Rare | Impaired dimer stability and catalytic function |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; severe deficiency phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations (e.g., p.Arg78His, p.Met1Val) reduce or abolish PGAM1 enzymatic activity, causing metabolic myopathy.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in PGAM1.
Dominant Negative (DN)
No dominant-negative mutations described for PGAM1.
View complete mutation data：
Gene Ontology (GO)
| • phosphoglycerate mutase activity (GO:0004619) | • glycolytic process (GO:0006096) |
| • gluconeogenesis (GO:0006094) | • cytosol (GO:0005829) |
| • isomerase activity (GO:0016853) |
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• Carbon metabolism (KEGG: hsa01200)
• Biosynthesis of amino acids (KEGG: hsa01230)
• HIF-1 signaling pathway (KEGG: hsa04066)
Protein Summary
PGAM1 is a 254-amino acid homodimeric enzyme that catalyzes the reversible conversion of 3-phosphoglycerate to 2-phosphoglycerate, a critical step in glycolysis. It is ubiquitously expressed with highest levels in skeletal muscle and heart. PGAM1 is frequently upregulated in cancers, contributing to the Warburg effect, and is considered a potential therapeutic target. Mutations in PGAM1 cause autosomal recessive phosphoglycerate mutase deficiency, a rare glycogen storage disease affecting muscle.
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