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PYGM
glycogen phosphorylase, muscle associated
The PYGM gene provides instructions for producing myophosphorylase, an enzyme critical for breaking down glycogen in muscle cells to provide energy. The PYGM gene is responsible for encoding myophosphorylase, a muscle-specific enzyme that plays a key role in glycogen metabolism.
PYGM is located on the long (q) arm of chromosome 11, at band 11q13.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The PYGM gene encodes muscle glycogen phosphorylase, also known as myophosphorylase. This enzyme is essential for muscle function, as it initiates the breakdown of glycogen stores within muscle cells. Glycogen is a complex carbohydrate that serves as the body's primary energy reserve.
Dysfunction of the PYGM gene can lead to impaired glycogenolysis, the process of breaking down glycogen, particularly in muscle tissue. This impairment can result in reduced energy availability for muscle activity, impacting overall muscle performance and health.
What the gene does
The PYGM gene directs the synthesis of myophosphorylase, an enzyme exclusively found in muscle cells. Myophosphorylase is one of three related glycogen phosphorylase enzymes involved in glycogen breakdown. Its specific role is to catalyse the first step in glycogenolysis within muscles, converting glycogen into glucose-1-phosphate. This molecule is then further processed to yield glucose, a simple sugar.
Glucose serves as the main fuel source for most cells, including muscle cells during activity. By breaking down glycogen, myophosphorylase ensures a steady supply of glucose for muscle contraction and other energy-dependent processes. A deficiency or absence of functional myophosphorylase can therefore severely compromise the ability of muscles to generate energy, especially during physical exertion.
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Chromosome location
The PYGM gene is situated on chromosome 11, specifically at position 11q13.1. This location refers to the long (q) arm of chromosome 11, within region 1, band 3, sub-band 1.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the PYGM gene can affect the structure and function of the myophosphorylase enzyme. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, potentially leading to a non-functional or deficient enzyme. Such alterations can impair the muscle's ability to metabolise glycogen effectively.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in the PYGM gene are primarily associated with an inherited metabolic disorder known as Glycogen Storage Disease Type V (GSD V), also referred to as McArdle disease. This condition is inherited in an autosomal recessive manner. It results from a deficiency in myophosphorylase, which hinders the breakdown of glycogen in muscle tissue.
Inheritance pattern
Conditions caused by pathogenic PYGM variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The PYGM gene is included in several NHS England Genomic Medicine Service approved panels. These include panels for Acute rhabdomyolysis, Foetal anomalies, Glycogen storage disease, Glycogen storage disease V, Hyperammonaemia, Likely inborn error of metabolism, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies, Retinal disorders, Rhabdomyolysis and metabolic muscle disorders, Skeletal Muscle Channelopathies, Skeletal muscle channelopathy, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is Glycogen Storage Disease Type V (McArdle disease)?
Glycogen Storage Disease Type V is an inherited disorder caused by a deficiency of the myophosphorylase enzyme, which is encoded by the PYGM gene. This deficiency prevents muscles from breaking down glycogen for energy, leading to symptoms like muscle pain, fatigue, and cramping during exercise.
How is Glycogen Storage Disease Type V inherited?
Glycogen Storage Disease Type V is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the altered PYGM gene (one from each parent) to develop the condition. Individuals with only one altered copy are typically carriers and do not show symptoms.
What is the role of myophosphorylase in the body?
Myophosphorylase is an enzyme found exclusively in muscle cells. Its primary function is to initiate the breakdown of glycogen, a stored form of glucose, into glucose-1-phosphate. This process is crucial for providing energy to muscles, especially during physical activity.
References
- Nogales-Gadea G, Rubio JC, Fernandez-Cadenas I. Expression of the muscle glycogen phosphorylase gene in patients with McArdle disease: the role of nonsense-mediated mRNA decay. Human mutation. 2008. PMID: 17994553
- Nogales-Gadea G, Arenas J, Andreu AL. Molecular genetics of McArdle's disease. Current neurology and neuroscience reports. 2007. PMID: 17217859
- Aquaron R, Bergé-Lefranc JL, Pellissier JF. Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: identification of 10 new mutations. Absence of genotype-phenotype correlation. Neuromuscular disorders : NMD. 2007. PMID: 17324573
- Deschauer M, Morgenroth A, Joshi PR. Analysis of spectrum and frequencies of mutations in McArdle disease. Identification of 13 novel mutations. Journal of neurology. 2007. PMID: 17404776
- Bruno C, Cassandrini D, Martinuzzi A. McArdle disease: the mutation spectrum of PYGM in a large Italian cohort. Human mutation. 2006. PMID: 16786513