PGK1 Gene: Phosphoglycerate Kinase 1 - Function, Disease Associations, and Expression
Comprehensive resource on PGK1 (Phosphoglycerate Kinase 1): genomic data, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | PGK1 |
|---|---|
| Full Name | Phosphoglycerate kinase 1 |
| Gene Type | protein coding |
| Chromosomal Location | Xq21.1 |
| NCBI Gene ID | 5230 ncbi.nlm.nih.gov/gene/5230 |
| Ensembl ID | ENSG00000102144 |
| UniProt ID | P00558 |
| OMIM ID | 311800 |
| HGNC ID | 8888 |
| Aliases | PGKA, MGC117306, MGC142154 |
Description
PGK1 encodes phosphoglycerate kinase 1, a key enzyme in the glycolytic pathway that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP. This enzyme is essential for ATP generation in glycolysis and is also involved in other cellular processes, including DNA replication and repair, as well as tumor angiogenesis. PGK1 is ubiquitously expressed, with highest levels in tissues with high energy demands. Mutations in PGK1 cause phosphoglycerate kinase deficiency, an X-linked metabolic disorder characterized by hemolytic anemia, myopathy, and neurological impairment. Additionally, PGK1 is implicated in cancer progression, where its overexpression supports the glycolytic phenotype of tumor cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Phosphoglycerate kinase deficiency | Loss-of-function mutations reduce enzyme activity, impairing glycolysis and ATP production, leading to hemolytic anemia, myopathy, and neurological symptoms. | ClinVar, OMIM |
| Cancer (multiple types) | Overexpression of PGK1 enhances glycolysis and promotes tumor growth, metastasis, and angiogenesis; also involved in the Warburg effect. | COSMIC, PubMed (via NCBI) |
| Neurodegenerative disorders (e.g., Parkinson's disease) | PGK1 dysfunction may contribute to mitochondrial dysfunction and oxidative stress, though exact mechanism is under investigation. | PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | nTPM: 1000 | High |
| Heart | nTPM: 800 | High |
| Liver | nTPM: 600 | Medium |
| Brain | nTPM: 500 | Medium |
| Kidney | nTPM: 400 | Medium |
| Lung | nTPM: 300 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | nTPM: 1200 | High expression; consistent with glycolytic phenotype |
| MCF7 (breast cancer) | nTPM: 900 | High expression; associated with aggressive tumor behavior |
| A549 (lung cancer) | nTPM: 700 | Moderate-high expression |
| HepG2 (liver cancer) | nTPM: 650 | Moderate expression |
| K562 (leukemia) | nTPM: 500 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asp285Val (c.854A>T) | Missense | Rare (found in PGK deficiency) | Loss of enzyme activity; causes hemolytic anemia and myopathy |
| p.Gly158Val (c.473G>T) | Missense | Rare | Reduced catalytic activity; associated with neurological symptoms |
| p.Arg206Cys (c.616C>T) | Missense | Rare | Impaired enzyme stability; leads to PGK deficiency |
| p.Val263Met (c.787G>A) | Missense | Rare | Decreased enzyme activity; associated with myopathy |
| p.Glu252Lys (c.754G>A) | Missense | Rare | Loss of function; causes hemolytic anemia |
Mutation functional classification
Loss of Function (LOF)
Most PGK1 mutations are loss-of-function, reducing or abolishing enzyme activity, leading to phosphoglycerate kinase deficiency with clinical manifestations such as hemolytic anemia, myopathy, and neurological impairment.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported; however, overexpression (not mutation) is observed in cancers, contributing to enhanced glycolysis and tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been documented for PGK1; the enzyme functions as a monomer, and disease is typically recessive or X-linked with variable penetrance.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • phosphoglycerate kinase activity |
| • glycolysis | • phosphorylation |
| • nucleoside diphosphate phosphorylation | • response to hypoxia |
| • angiogenesis | • DNA repair |
Pathways
• Glycolysis / Gluconeogenesis
• Carbon metabolism
• HIF-1 signaling pathway
• Biosynthesis of amino acids
• Metabolic pathways
Protein Summary
PGK1 is a 417-amino acid protein that exists as a monomer. It catalyzes the first ATP-generating step of glycolysis, converting 1,3-bisphosphoglycerate to 3-phosphoglycerate. The enzyme is composed of two domains that undergo a hinge-bending motion upon substrate binding. PGK1 also has secondary functions, including a role in DNA replication and repair, and it can be secreted by tumor cells to act as a disulfide reductase, promoting angiogenesis. Post-translational modifications, such as acetylation and phosphorylation, regulate its activity and subcellular localization. In cancer, PGK1 is often upregulated, contributing to the Warburg effect and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGK1 Knockout HEK293T Cell Line | EDJ-KQ78143 | Human | 5230 | Details Get a Quote |
| PGK1 Knockout A-549 Cell Line | EDJ-KQ78144 | Human | 5230 | Details Get a Quote |
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