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PGK1
phosphoglycerate kinase 1
The PGK1 gene encodes phosphoglycerate kinase 1, an enzyme fundamental to the glycolysis pathway, which is essential for cellular energy production. The PGK1 gene provides instructions for synthesising the phosphoglycerate kinase enzyme.
PGK1 is located on the long (q) arm of chromosome X, at band Xq21.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The PGK1 gene is responsible for producing phosphoglycerate kinase 1, an enzyme found in cells and tissues throughout the body. This enzyme is a key component of glycolysis, the metabolic pathway that converts glucose into energy. The adenosine triphosphate (ATP) generated is crucial for various cellular functions.
While its primary role is in glycolysis, phosphoglycerate kinase 1 may also have other functions within cells; however, these are not yet fully understood.
What the gene does
The phosphoglycerate kinase enzyme, produced from the PGK1 gene, performs a critical step in glycolysis. Within this pathway, glucose is broken down to produce energy for the cell. Specifically, the enzyme catalyses the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate.
This reaction is significant because it generates one molecule of adenosine triphosphate (ATP), which is the principal energy currency for cellular processes. Therefore, the proper function of the PGK1 enzyme is essential for maintaining cellular energy supplies.
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Chromosome location
The PGK1 gene is located on the X chromosome at position Xq21.1. This genomic location means that PGK1 is an X-linked gene, which can influence its inheritance pattern and how associated conditions manifest in individuals.
Protein structure
The PGK1 protein is composed of 417 amino acids. Between amino acids 38 and 43, there is a mitochondrial targeting region. This sequence is exposed after modification by an enzyme called PIN1, allowing the TOM protein complex to recognise it and transport the protein into the mitochondria.
Key variants
Genetic variations within the PGK1 gene can impact the structure and function of the phosphoglycerate kinase enzyme. These variations, which may include single amino acid changes, can disrupt the enzyme's ability to efficiently catalyse its biochemical reaction in glycolysis, leading to altered energy production. The severity and type of health implications depend on the specific genetic change.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.491A>T | p.Asp164Val | Pathogenic | ★★☆☆ | Inborn genetic diseases |
A353P | - | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
G213G | - | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
G317D | - | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
G372S | - | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
c.1132A>C | p.Thr378Pro | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
c.140T>A | p.Ile47Asn | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
c.854A>T | p.Asp285Val | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
c.959G>A | p.Ser320Asn | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
PGK1, IVS4, G-T, 417+1 | - | Pathogenic | - | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variations in the PGK1 gene are primarily associated with phosphoglycerate kinase deficiency. At least 18 mutations in this gene have been identified in scientific literature. The condition can manifest differently across individuals, with symptoms documented in scientific literature including chronic haemolytic anaemia with or without neurological problems.
No disease links recorded for this gene in our reference set.
UK clinical status
The PGK1 gene is included in several panels within the NHS Genomic Medicine Service's PanelApp, including panels for Acute rhabdomyolysis, Glycogen storage disease, Intellectual disability, and Likely inborn error of metabolism, among others. Additional panels include Rhabdomyolysis and metabolic muscle disorders, Undiagnosed metabolic disorders, and DDG2P (Developmental Disorders Genotype-Phenotype Database).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the PGK1 gene?
The PGK1 gene provides instructions for the phosphoglycerate kinase enzyme, which is crucial for glycolysis. This enzyme helps convert glucose into adenosine triphosphate (ATP), the main energy source for cells.
What health conditions are associated with changes in the PGK1 gene?
Variations in the PGK1 gene are primarily linked to phosphoglycerate kinase deficiency. This condition can cause symptoms such as chronic haemolytic anaemia or neurological issues.
Is the PGK1 gene tested within the NHS in the UK?
Yes, the PGK1 gene is included in several NHS Genomic Medicine Service PanelApp panels, including those for Acute rhabdomyolysis, Glycogen storage disease, and Likely inborn error of metabolism, among others.
References
- Spiegel R, Gomez EA, Akman HO. Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations. Neuromuscular disorders : NMD. 2009. PMID: 19157875
- Beutler E. PGK deficiency. British journal of haematology. 2007. PMID: 17222195
- Svaasand EK, Aasly J, Landsem VM. Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle & nerve. 2007. PMID: 17661373
- Noel N, Flanagan JM, Ramirez Bajo MJ. Two new phosphoglycerate kinase mutations associated with chronic haemolytic anaemia and neurological dysfunction in two patients from Spain. British journal of haematology. 2006. PMID: 16412025
- Flanagan JM, Rhodes M, Wilson M. The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA. British journal of haematology. 2006. PMID: 16740138