On this page
PFKM
phosphofructokinase, muscle
The PFKM gene encodes a subunit of the phosphofructokinase enzyme, critical for breaking down glycogen to supply energy, particularly in muscle cells. The PFKM gene is responsible for producing a specific component of the phosphofructokinase enzyme.
PFKM is located on the long (q) arm of chromosome 12, at band 12q13.11. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 12 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The PFKM gene, also known as phosphofructokinase, muscle type, is instrumental in cellular energy metabolism. It provides the genetic blueprint for a crucial subunit of the phosphofructokinase enzyme, which is essential for the breakdown of glycogen.
Glycogen serves as a primary energy reserve within the body. The enzyme produced from the PFKM gene is particularly active in muscle tissue, where it facilitates the conversion of glycogen into a usable form of energy. Variations in this gene can impact the body's ability to generate energy, especially during physical activity.
What the gene does
The PFKM gene directs the synthesis of one specific subunit of the phosphofructokinase enzyme. This enzyme is a complex structure typically composed of four subunits, with different combinations found in various body tissues. In skeletal muscles, the phosphofructokinase enzyme is uniquely formed from subunits derived solely from the PFKM gene.
This enzyme is critical for glycolysis, a metabolic pathway that converts glucose into energy. Specifically, the phosphofructokinase enzyme acts as a regulatory point in glycolysis by catalysing the conversion of fructose-6-phosphate to fructose 1,6-bisphosphate. This step is crucial for breaking down glycogen, a stored form of glucose, into simple sugars that muscle cells can use for immediate energy.
Video: Genetics 101
Chromosome location
The PFKM gene is situated on chromosome 12 at position 12q13.11. This specific genomic location indicates its precise address within the human genome. The gene's location is important for understanding its organisation and how genetic changes might impact its function.
Protein structure
The protein encoded by the PFKM gene is 780 amino acids long and features distinct functional regions. It contains an N-terminal catalytic PFK domain 1, spanning amino acids 2-390, which is involved in the enzyme's catalytic activity. An Interdomain linker, from amino acids 391-401, connects the two main domains. The C-terminal regulatory PFK domain 2, located from amino acids 402-780, likely plays a role in regulating the enzyme's activity.
Key variants
Variants within the PFKM gene can influence the function of the phosphofructokinase enzyme. These genetic changes can affect the enzyme's structure, stability, or its ability to effectively break down glycogen. The impact of such variants can range from mild to severe, depending on how significantly they impair the enzyme's activity and, consequently, cellular energy production.
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.1057C>T | p.Gln353Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.1294C>T | p.Arg432Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.1321G>T | p.Glu441Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.1338del | p.Gln447fs | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.1458dup | p.Lys487Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.1807C>T | p.Arg603Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.2080_2081del | p.Ser694fs | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.381_385dup | p.Arg129fs | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.395G>A | p.Trp132Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
c.736C>T | p.Arg246Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glycogen storage disease, type VII |
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
Changes in the PFKM gene are associated with inherited conditions primarily affecting muscle metabolism. These conditions often stem from an inability of muscle cells to properly break down glycogen for energy. One such condition linked to PFKM gene mutations is Glycogen storage disease type VII, which can result in symptoms such as muscle weakness and cramps.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the PFKM gene is included on several NHS Genomic Medicine Service clinical panels. These include panels for Acute rhabdomyolysis, Arthrogryposis, Cytopenias and congenital anaemias, Foetal anomalies, Glycogen storage disease, Likely inborn error of metabolism, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies, Rare anaemia, Rhabdomyolysis and metabolic muscle disorders, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the PFKM gene?
The PFKM gene provides instructions for a subunit of the phosphofructokinase enzyme, which is crucial for breaking down glycogen into usable energy, especially within muscle cells.
What happens if the PFKM gene has a mutation?
Mutations in the PFKM gene can impair the function of the phosphofructokinase enzyme, leading to conditions like Glycogen storage disease type VII, where muscles struggle to produce energy from glycogen.
Is the PFKM gene relevant for genetic testing in the UK?
Yes, the PFKM gene is included in several NHS Genomic Medicine Service clinical panels for various conditions, including metabolic muscle disorders and glycogen storage diseases.
References
- Schöneberg T, Kloos M, Brüser A. Structure and allosteric regulation of eukaryotic 6-phosphofructokinases. Biological chemistry. 2013. PMID: 23729568
- Vives-Corrons JL, Koralkova P, Grau JM. First description of phosphofructokinase deficiency in spain: identification of a novel homozygous missense mutation in the PFKM gene. Frontiers in physiology. 2013. PMID: 24427140
- Brüser A, Kirchberger J, Kloos M. Functional linkage of adenine nucleotide binding sites in mammalian muscle 6-phosphofructokinase. The Journal of biological chemistry. 2012. PMID: 22474333