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PGM3
phosphoglucomutase 3
The PGM3 gene encodes phosphoglucomutase 3, an enzyme vital for glycosylation, a process that modifies proteins and lipids, and is particularly important for immune system function. The PGM3 gene provides instructions for producing the phosphoglucomutase 3 enzyme, which plays a critical role in glycosylation.
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, or phosphoglucomutase 3, is responsible for an enzyme involved in glycosylation, a key biological process. Glycosylation modifies proteins and lipids by attaching complex sugar chains, known as oligosaccharides, which allows them to carry out a broader range of functions within the body. Disruptions in PGM3 function can have wide-ranging effects, particularly impacting immune system health.
Variations within the PGM3 gene have been linked to a specific inherited condition called PGM3-congenital disorder of glycosylation (PGM3-CDG). This condition primarily affects the immune system but can also manifest with other symptoms.
What the gene does
The PGM3 enzyme facilitates a critical step in the glycosylation pathway. Specifically, it converts N-acetylglucosamine-6-phosphate into N-acetylglucosamine-1-phosphate. This conversion is essential for the synthesis of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc serves as a vital donor molecule, providing the sugar units needed to build and extend oligosaccharide chains during the glycosylation process.
Glycosylation is a ubiquitous process that impacts a vast array of cellular functions, including cell-to-cell communication, immune response, and protein stability. The proper functioning of PGM3 is therefore indispensable for maintaining numerous physiological processes, with a notable impact on the development and regulation of the immune system.
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Chromosome location
The PGM3 gene is situated on chromosome 6, specifically at band 6q14.1. This location refers to the long arm (q) of chromosome 6, within region 14, sub-band 1. The precise chromosomal address helps in understanding the gene's genetic context and its potential proximity to other genes.
Protein structure
The PGM3 gene codes for a protein consisting of 542 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the PGM3 gene can impact the function of the phosphoglucomutase 3 enzyme. These variations, often referred to as mutations, can alter the enzyme's structure or activity, leading to impaired glycosylation processes. The specific effects of a variant depend on its nature and location within the gene.
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 in the PGM3 gene are known to cause PGM3-congenital disorder of glycosylation (PGM3-CDG). This condition predominantly affects the immune system, leading to impaired immune function. Individuals with PGM3-CDG may also experience distinct facial features, intellectual disability, and developmental delays, reflecting the broad importance of glycosylation.
No disease links recorded for this gene in our reference set.
UK clinical status
The PGM3 gene is included in several NHS England Genomic Medicine Service approved panels. These include panels for Congenital disorders of glycosylation, COVID-19 research, DDG2P, Foetal anomalies (R21), Intellectual disability, Likely inborn error of metabolism (R98), Primary immunodeficiency or monogenic inflammatory bowel disease (R15), Severe multi-system atopic disease with high IgE, Skeletal dysplasia (R104), and Undiagnosed metabolic disorders.
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 an enzyme called phosphoglucomutase 3, which is crucial for glycosylation. This process involves adding sugar chains to proteins and fats, allowing them to perform various cellular functions, particularly in the immune system.
What condition is associated with mutations in the PGM3 gene?
Mutations in the PGM3 gene are associated with PGM3-congenital disorder of glycosylation (PGM3-CDG). This condition mainly affects the immune system, leading to immune deficiency, and can also present with distinctive facial features, intellectual disability, and developmental delay.
Is the PGM3 gene relevant to NHS genomic testing?
Yes, the PGM3 gene is included in several NHS England Genomic Medicine Service approved panels. These cover conditions such as congenital disorders of glycosylation, primary immunodeficiency, intellectual disability, and skeletal dysplasia, among others.
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