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PGM3
phosphoglucomutase 3
The PGM3 gene provides instructions for an enzyme called phosphoglucomutase 3, which is crucial for glycosylation, a process involving the attachment of sugar molecules to proteins and fats. PGM3 is a gene that codes for the phosphoglucomutase 3 enzyme, an essential component of the glycosylation pathway.
PGM3 is located on the long (q) arm of chromosome 6, at band 6q14.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The PGM3 gene, also known as phosphoglucomutase 3, is responsible for producing an enzyme central to cellular metabolism. This enzyme plays a significant role in glycosylation, a complex biochemical process where sugar chains are added to proteins and lipids.
Glycosylation is fundamental for the proper function of many proteins, influencing their structure, stability, and interactions within the body. Inherited changes in the PGM3 gene can disrupt this vital process, leading to a range of health issues, particularly affecting the immune system.
What the gene does
The PGM3 enzyme facilitates a critical step in glycosylation. Specifically, it converts N-acetylglucosamine-6-phosphate into N-acetylglucosamine-1-phosphate. This conversion is necessary for the production of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc).
UDP-GlcNAc serves as a donor molecule, providing sugars that are then incorporated into growing oligosaccharide chains during glycosylation. These oligosaccharides are attached to proteins and fats, thereby modifying them to perform diverse biological roles. Proper PGM3 function is therefore essential for the creation of correctly glycosylated molecules, which are involved in immune response, cell signalling, and structural integrity.
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Chromosome location
The PGM3 gene is located on chromosome 6, specifically at position 6q14.1. This genomic location specifies the precise region on the long arm (q) of chromosome 6 where the gene resides. Understanding its chromosomal position helps in mapping and studying genetic disorders linked to this region.
Protein structure
The PGM3 gene codes for a protein that is 542 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in the PGM3 gene can alter the function of the phosphoglucomutase 3 enzyme. These variants range from single nucleotide changes to larger deletions or insertions, and their impact on the enzyme's activity can vary significantly. Pathogenic variants can impair the enzyme's ability to facilitate glycosylation, leading to adverse health effects.
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.1016AAG[1] | p.Glu340del | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.1153_1157del | p.Met385fs | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.1197_1201del | p.Arg399fs | Pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.162del | p.Lys54fs | Pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.-2-185C>T | Q24* | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.310A>T | p.Arg104Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.378dup | p.Arg127Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.398_413del | p.Ser133fs | Pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.64C>T | p.Gln22Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 23 |
c.737A>G | p.Asn246Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
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
Mutations within the PGM3 gene are known to cause PGM3-congenital disorder of glycosylation (PGM3-CDG). This condition is primarily characterised by its impact on the immune system, leading to impaired immune function. Individuals affected by PGM3-CDG may also exhibit distinct facial features, intellectual disability, and developmental delays. At least 16 different mutations in PGM3 have been identified as causes of PGM3-CDG.
No disease links recorded for this gene in our reference set.
UK clinical status
The PGM3 gene is included in several panels within the UK's NHS Genomic Medicine Service PanelApp. It is listed as 'green' for conditions such as Congenital disorders of glycosylation, COVID-19 research, DDG2P, Foetal anomalies, Intellectual disability, Likely inborn error of metabolism, Primary immunodeficiency or monogenic inflammatory bowel disease, Severe multi-system atopic disease with high IgE, Skeletal dysplasia, and Undiagnosed metabolic disorders, indicating its established clinical relevance.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the PGM3 gene?
The PGM3 gene provides instructions for the phosphoglucomutase 3 enzyme, which is crucial for glycosylation. This enzyme converts N-acetylglucosamine-6-phosphate to N-acetylglucosamine-1-phosphate, a key step in producing molecules needed to attach sugars to proteins and fats.
What health conditions are associated with PGM3 gene mutations?
Mutations in the PGM3 gene are associated with PGM3-congenital disorder of glycosylation (PGM3-CDG). This condition primarily affects the immune system, but can also lead to distinct facial features, intellectual disability, and developmental delays.
Where is the PGM3 gene located?
The PGM3 gene is located on chromosome 6, specifically at band 6q14.1. This position helps identify and study the gene's involvement in genetic disorders.
References
- Jaeken J, Lefeber DJ, Matthijs G. Clinical Utility Gene Card for: PGM3 defective congenital disorder of glycosylation. European journal of human genetics : EJHG. 2019. PMID: 31231132
- Lundin KE, Hamasy A, Backe PH. Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene. Clinical immunology (Orlando, Fla.). 2015. PMID: 26482871
- Sassi A, Lazaroski S, Wu G. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. The Journal of allergy and clinical immunology. 2014. PMID: 24698316
- Stray-Pedersen A, Backe PH, Sorte HS. PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. American journal of human genetics. 2014. PMID: 24931394
- Yang L, Fliegauf M, Grimbacher B. Hyper-IgE syndromes: reviewing PGM3 deficiency. Current opinion in pediatrics. 2014. PMID: 25365149