PYGM Gene (Glycogen Phosphorylase, Muscle Associated)
Essential enzyme in muscle glycogenolysis; mutations cause McArdle disease (Glycogen Storage Disease Type V).
Gene Information Card
| Symbol | PYGM |
|---|---|
| Full Name | Glycogen phosphorylase, muscle associated |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 5837 ncbi.nlm.nih.gov/gene/5837 |
| Ensembl ID | ENSG00000068976 |
| UniProt ID | P11217 |
| OMIM ID | 608455 |
| HGNC ID | 9726 |
| Aliases | PFBM, GSD5, MGP, PYGM |
Description
The PYGM gene encodes the muscle isoform of glycogen phosphorylase, a key enzyme that catalyzes the rate-limiting step in glycogenolysis, releasing glucose-1-phosphate from glycogen stores. This enzyme is primarily expressed in skeletal muscle, where it provides a rapid source of glucose for ATP production during exercise. Mutations in PYGM lead to a deficiency of muscle glycogen phosphorylase activity, resulting in Glycogen Storage Disease Type V (McArdle disease), characterized by exercise intolerance, muscle cramps, and myoglobinuria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Glycogen Storage Disease Type V (McArdle Disease) | Loss-of-function mutations in PYGM lead to a deficiency or absence of muscle glycogen phosphorylase activity. This impairs the breakdown of glycogen in skeletal muscle, blocking the generation of glucose-1-phosphate and subsequent ATP production during anaerobic exercise. The energy deficit causes muscle fatigue, cramps, and damage. | ClinVar, OMIM (608455), NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Skeletal Muscle | ~1000 | High |
| Heart | ~50 | Low |
| Brain | ~10 | Low |
| Liver | ~5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| Skeletal Muscle Myotubes | High | Primary cell type expressing PYGM |
| Cardiomyocytes | Low | Minimal expression compared to skeletal muscle |
| HepG2 (Liver) | Not detected | Liver isoform (PYGL) is expressed instead |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.Arg50Ter (R50X) | Nonsense | Common (~50% of alleles in some populations) | Premature stop codon, leading to a truncated, non-functional protein and complete loss of enzyme activity. |
| p.Gly205Ser (G205S) | Missense | Recurrent | Amino acid substitution that disrupts protein folding or catalytic function, resulting in reduced enzyme activity. |
| c.613G>A (p.Gly205Ser) | Missense | Recurrent | Same as above; a common pathogenic variant in McArdle disease. |
| p.Leu397Pro (L397P) | Missense | Rare | Alters protein structure, leading to enzyme instability and loss of function. |
Mutation functional classification
Loss of Function (LOF)
The vast majority of PYGM mutations are loss-of-function, leading to reduced or absent enzyme activity. This is the primary mechanism for McArdle disease, where the inability to break down glycogen in muscle causes the clinical phenotype.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PYGM. The enzyme's activity is tightly regulated, and any increase would likely be detrimental, but no such pathogenic variants are known.
Dominant Negative (DN)
No dominant-negative mutations have been described for PYGM. The disease is inherited in an autosomal recessive manner, indicating that a single functional allele is sufficient for normal enzyme activity.
View complete mutation data：
Gene Ontology (GO)
| • glycogen phosphorylase activity | • glycogen catabolic process |
| • carbohydrate metabolic process | • response to glucose |
| • muscle contraction |
Pathways
• Glycogenolysis
• Glycogen metabolism
• Starch and sucrose metabolism
Protein Summary
The PYGM protein is a homodimer of 842 amino acids (UniProt P11217). It functions as a key regulatory enzyme in muscle energy metabolism, catalyzing the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate. The enzyme is allosterically regulated by AMP, ATP, and glucose-6-phosphate, and is activated by phosphorylation via phosphorylase kinase in response to hormonal and neuronal signals. Its structure includes a glycogen-binding domain and a catalytic site. Deficiency of this protein is the molecular basis of McArdle disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PYGM Knockout HEK293 Cell Line | EDJ-KQ5617 | Human | 5837 | Details Get a Quote |
| PYGM Knockout HeLa Cell Line | EDJ-KQ54284 | Human | 5837 | Details Get a Quote |
| PYGM Knockout A-549 Cell Line | EDJ-KQ62777 | Human | 5837 | Details Get a Quote |
| PYGM Knockout HCT 116 Cell Line | EDJ-KQ71244 | Human | 5837 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
