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PYGL
glycogen phosphorylase L
The PYGL gene provides instructions for making liver glycogen phosphorylase, an enzyme essential for breaking down glycogen in the liver to release glucose. The PYGL gene encodes the liver-specific form of glycogen phosphorylase.
PYGL is located on the long (q) arm of chromosome 14, at band 14q22.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The PYGL gene encodes the liver glycogen phosphorylase enzyme, which is vital for maintaining normal blood glucose levels. This enzyme's primary function is to break down glycogen, a complex carbohydrate stored predominantly in the liver, into glucose-1-phosphate. This product is then converted into glucose, which can be released into the bloodstream to provide energy for the body, especially during periods of fasting or increased energy demand.
Disruptions to the function of the PYGL gene can lead to metabolic disorders, specifically conditions where glycogen cannot be properly broken down. Understanding the role of PYGL is therefore important for diagnosing and managing inherited metabolic conditions that affect glucose regulation.
What the gene does
The PYGL gene directs the synthesis of liver glycogen phosphorylase, an enzyme found exclusively in liver cells. This enzyme is one of three related glycogen phosphorylases, with the others active in the brain and muscle tissues. The liver-specific form is crucial for systemic glucose regulation.
The liver glycogen phosphorylase enzyme acts on glycogen, a branched polysaccharide that serves as the main glucose storage molecule in animals. Through a process called glycogenolysis, the enzyme catalyses the cleavage of alpha-1,4 glycosidic bonds in glycogen, releasing glucose-1-phosphate molecules. These glucose-1-phosphate units are subsequently converted to glucose, which is then released from the liver into the bloodstream to supply other tissues with energy. This mechanism is particularly important for maintaining blood glucose during fasting periods and ensuring a steady energy supply for the brain and other organs.
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Chromosome location
The PYGL gene is located on chromosome 14, specifically at band 14q22.1. The gene provides instructions for a protein that is 847 amino acids long. Its precise genomic position helps to understand its organisation within the human genome.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the PYGL gene can alter the structure and function of the liver glycogen phosphorylase enzyme. These genetic changes can range from single amino acid substitutions to larger deletions or insertions, and they may impair the enzyme's ability to efficiently break down glycogen. The consequence of such variants is often a reduction in enzyme activity, leading to the accumulation of glycogen in liver cells.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in the PYGL gene are associated with glycogen storage disease type VI (GSDVI). This condition is characterised by the liver's inability to properly break down glycogen, leading to its accumulation. Symptoms can include an enlarged liver, low blood glucose levels (hypoglycaemia), and impaired growth. GSDVI is inherited in an autosomal recessive pattern.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PYGL 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 PYGL gene is recognised in the UK by NHS England's Genomic Medicine Service, being listed on several diagnostic panels within PanelApp. It is included in the 'Glycogen storage disease' (R274), 'Ketotic hypoglycaemia', 'Likely inborn error of metabolism' (R98), and 'Undiagnosed metabolic disorders' panels, all with a 'green' status, indicating strong evidence for its role in disease.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the PYGL gene?
The PYGL gene provides instructions for making liver glycogen phosphorylase, an enzyme crucial for breaking down glycogen in the liver. This process releases glucose, which is essential for maintaining blood sugar levels and providing energy for the body.
What condition is associated with variants in the PYGL gene?
Variants in the PYGL gene are associated with glycogen storage disease type VI (GSDVI). This inherited metabolic disorder results from the liver's inability to properly break down glycogen, leading to its accumulation in liver cells.
How is glycogen storage disease type VI inherited?
Glycogen storage disease type VI, caused by pathogenic variants in the PYGL gene, is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered gene, one from each parent, to develop the condition.
References
- Beauchamp NJ, Taybert J, Champion MP. High frequency of missense mutations in glycogen storage disease type VI. Journal of inherited metabolic disease. 2007. PMID: 17705025
- Burwinkel B, Bakker HD, Herschkovitz E. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. American journal of human genetics. 1998. PMID: 9529348
- Chang S, Rosenberg MJ, Morton H. Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI. Human molecular genetics. 1998. PMID: 9536091
- Adam MP, Bick S, Mirzaa GM. Glycogen Storage Disease Type VI. 1993. PMID: 20301760