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PGM1
phosphoglucomutase 1
PGM1 is located on the short (p) arm of chromosome 1, at band 1p31.3. Arm ratio per GRCh38 - banding schematic.
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Overview
PGM1 is located on chromosome 1 and encodes phosphoglucomutase 1, a metabolic enzyme that acts as a gateway between glycogen storage pathways and glucose utilisation routes. The enzyme functions bidirectionally, allowing cells to either build glycogen reserves when energy is plentiful or release glucose for immediate use during fasting or exercise.
This gene is expressed in most tissues but plays a particularly important role in liver and muscle, where glycogen serves as the primary short-term energy reserve. The phosphoglucomutase 1 enzyme belongs to a family of enzymes that manage phosphorylated sugar intermediates, ensuring smooth transitions between different metabolic states throughout the day.
What the gene does
Phosphoglucomutase 1 catalyses the interconversion of glucose-1-phosphate and glucose-6-phosphate, two sugar molecules that differ only in where a phosphate group attaches to the glucose ring. This seemingly small chemical rearrangement has profound metabolic consequences, as glucose-1-phosphate is the direct product of glycogen breakdown, whilst glucose-6-phosphate sits at the crossroads of multiple pathways including glycolysis, the pentose phosphate pathway, and glucose synthesis.
The enzyme operates through a two-step phosphoryl transfer mechanism. A phosphate group from the active site is first transferred to the substrate, creating a short-lived intermediate, then the product is released with the phosphate in its new position. This ping-pong mechanism requires precise coordination of the enzyme's shape changes to ensure the reaction proceeds efficiently in either direction depending on cellular needs.
In the liver, phosphoglucomutase 1 activity enables the organ to respond to hormonal signals by either storing glucose as glycogen after meals or releasing glucose into the bloodstream during fasting. In muscle tissue, the enzyme supports the rapid mobilisation of glycogen to fuel contraction during physical activity.
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Chromosome location
PGM1 is positioned on the short arm of chromosome 1 at band 1p31.3. This chromosomal region contains numerous genes involved in metabolic processes. The genomic structure and total number of exons for PGM1 have been mapped, though detailed architectural features vary across transcript isoforms. The gene produces several alternatively spliced variants that may differ slightly in their tissue distribution or regulatory properties.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in PGM1 range from common single-nucleotide changes with minimal functional impact to rare alterations that significantly reduce enzyme activity. The pattern of inheritance for PGM1-related conditions can vary depending on the specific variant and phenotype. Some pathogenic variants cause disease when inherited from both parents, whilst other genetic contexts have been described in the literature with different inheritance patterns.
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.1086dup | p.Gly363fs | Pathogenic | ★★☆☆ | PGM1-congenital disorder of glycosylation |
c.1091del | p.Asn364fs | Pathogenic | ★★☆☆ | PGM1-congenital disorder of glycosylation |
c.1144+3A>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1378_1379del | p.Ala461fs | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.1495C>T | p.Arg499Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PGM1-related disorder |
c.1544G>A | p.Arg515Gln | Pathogenic/Likely pathogenic | ★★☆☆ | PGM1-congenital disorder of glycosylation |
c.649C>T | p.Arg217Ter | Pathogenic | ★★☆☆ | PGM1-congenital disorder of glycosylation |
c.871G>A | p.Gly291Arg | Pathogenic/Likely pathogenic | ★★☆☆ | PGM1-related disorder |
c.877C>T | p.Arg293Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PGM1-congenital disorder of glycosylation |
c.988G>C | p.Gly330Arg | Pathogenic/Likely pathogenic | ★★☆☆ | PGM1-related disorder |
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
Variants in PGM1 have been associated with a spectrum of metabolic disturbances affecting glycogen storage and utilisation. Individuals with reduced phosphoglucomutase 1 activity may experience difficulties maintaining stable blood glucose levels, particularly during periods of fasting or increased physical demand. The clinical presentation can range from isolated exercise intolerance to more complex multisystem features involving liver function, growth, and in some cases glycosylation abnormalities that affect multiple organ systems.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the PGM1 gene do?
PGM1 encodes an enzyme called phosphoglucomutase 1, which converts glucose-1-phosphate to glucose-6-phosphate and vice versa. This conversion is essential for both building up glycogen stores and breaking them down to release energy when needed.
Where in the body is PGM1 active?
Phosphoglucomutase 1 is expressed in most tissues throughout the body, with particularly high activity in the liver and skeletal muscle where glycogen metabolism is most active. The enzyme is also present in the heart, brain, and other organs that rely on glucose for energy.
How common are PGM1 variants?
Many people carry common variants in PGM1 that have little or no effect on enzyme function. Rare pathogenic variants that significantly impair phosphoglucomutase 1 activity are uncommon in the general population, though specific prevalence figures depend on the population studied and the variant in question.