PYGB Glycogen Phosphorylase Brain Form
Key enzyme in glycogen metabolism with roles in glycogen storage disease and cancer
Gene Information Card
| Symbol | PYGB |
|---|---|
| Full Name | Glycogen Phosphorylase B (Brain Form) |
| Gene Type | protein-coding |
| Chromosomal Location | 20p11.21 |
| NCBI Gene ID | 5834 ncbi.nlm.nih.gov/gene/5834 |
| Ensembl ID | ENSG00000101246 |
| UniProt ID | P11216 |
| OMIM ID | 138550 |
| HGNC ID | 9716 |
| Aliases | GPBB, glycogen phosphorylase brain |
Description
PYGB encodes the brain isoform of glycogen phosphorylase, which catalyzes the rate-limiting step in glycogenolysis, cleaving glycogen to glucose-1-phosphate. This enzyme is primarily expressed in brain and heart, and its activity is regulated by allosteric effectors and phosphorylation. Mutations in PYGB are associated with glycogen storage disease type XV (GSD15), characterized by exercise intolerance and cardiomyopathy. The gene is also implicated in cancer metabolism, where its overexpression supports tumor growth under hypoxic conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen Storage Disease XV (GSD15) | Loss-of-function mutations impair glycogen breakdown, leading to glycogen accumulation in muscle and heart, causing myopathy and cardiomyopathy. | ClinVar, OMIM |
| Breast Cancer | Overexpression of PYGB promotes glycogenolysis to fuel glycolysis and tumor proliferation under hypoxia. | COSMIC, NCBI PubMed |
| Colorectal Cancer | Elevated PYGB expression correlates with poor prognosis and increased metastatic potential via altered glucose metabolism. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Skeletal Muscle | 2.1 | Low |
| Liver | 0.5 | Not detected |
| Kidney | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression in neuronal cells |
| MCF7 (breast cancer) | 9.7 | Moderate expression, upregulated under hypoxia |
| HCT116 (colorectal) | 7.4 | Moderate expression, associated with metabolic reprogramming |
| HEK293 (embryonic kidney) | 3.1 | Low baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1462C>T (p.Arg488Trp) | Missense | <0.01% | Loss of function; associated with GSD15 |
| c.1720G>A (p.Gly574Ser) | Missense | <0.01% | Loss of function; reduced enzyme activity |
| c.1966C>T (p.Arg656Cys) | Missense | <0.01% | Loss of function; reported in GSD15 |
| c.1234A>G (p.Lys412Glu) | Missense | <0.01% | Likely benign; no known disease association |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg488Trp, p.Gly574Ser) reduce or abolish catalytic activity, leading to glycogen accumulation and GSD15.
Gain of Function (GOF)
Not reported in PYGB; gain-of-function mutations are not documented in current databases.
Dominant Negative (DN)
Not reported; no evidence for dominant-negative effects in PYGB.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycogenolysis (Reactome: R-HSA-70221)
• Glucose metabolism (KEGG: hsa00010)
• Hypoxia-inducible factor (HIF) signaling (Reactome: R-HSA-1234174)
Protein Summary
PYGB encodes the brain isoform of glycogen phosphorylase (GPBB), a 843-amino acid homodimeric enzyme that catalyzes the phosphorolysis of glycogen to glucose-1-phosphate. The protein contains a pyridoxal phosphate cofactor binding site and is regulated by allosteric effectors (AMP, glucose-6-phosphate) and phosphorylation by phosphorylase kinase. GPBB is predominantly expressed in brain and heart, where it supplies glucose-1-phosphate for glycolysis and energy production. Mutations cause glycogen storage disease XV, while overexpression in cancers supports the Warburg effect.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PYGB Knockout HEK293 Cell Line | EDJ-KQ5619 | Human | 5834 | Details Get a Quote |
| PYGB Knockout HCT 116 Cell Line | EDJ-KQ28923 | Human | 5834 | Details Get a Quote |
| PYGB Knockout HeLa Cell Line | EDJ-KQ28924 | Human | 5834 | Details Get a Quote |
| PYGB Knockout A-549 Cell Line | EDJ-KQ27660 | Human | 5834 | Details Get a Quote |
