PHKA2: Phosphorylase Kinase Regulatory Subunit Alpha 2
A key regulator of glycogen metabolism linked to glycogen storage disease type IXa
Gene Information Card
| Symbol | PHKA2 |
|---|---|
| Full Name | Phosphorylase Kinase Regulatory Subunit Alpha 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.13 |
| NCBI Gene ID | 5256 ncbi.nlm.nih.gov/gene/5256 |
| Ensembl ID | ENSG00000131016 |
| UniProt ID | P46019 |
| OMIM ID | 300798 |
| HGNC ID | 8926 |
| Aliases | PHKLA, PYK, GSD9A, XLG |
Description
The PHKA2 gene encodes the alpha-2 regulatory subunit of phosphorylase kinase (PhK), a key enzyme in glycogen metabolism. PhK phosphorylates and activates glycogen phosphorylase, which catalyzes the breakdown of glycogen to glucose-1-phosphate. Mutations in PHKA2 cause X-linked liver glycogen storage disease type IXa (GSD IXa), characterized by hepatomegaly, hypoglycemia, and growth retardation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease type IXa (GSD IXa) | Loss-of-function mutations in PHKA2 impair PhK activity, reducing glycogen phosphorylase activation and leading to glycogen accumulation in the liver. | ClinVar, OMIM |
| X-linked liver glycogenosis (XLG) | Same mechanism as GSD IXa; PHKA2 mutations disrupt the regulatory subunit, causing deficient PhK activity in liver. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 15.2 | Medium |
| Kidney | 8.1 | Low |
| Heart | 6.5 | Low |
| Skeletal Muscle | 4.3 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 12.5 | Hepatocyte-derived line |
| HEK293 (embryonic kidney) | 7.8 | Moderate expression |
| K562 (leukemia) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1018C>T (p.Arg340*) | Nonsense | Rare | Loss of function; truncation of alpha subunit |
| c.361G>A (p.Gly121Arg) | Missense | Rare | Loss of function; disrupts regulatory domain |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; prevents translation |
Mutation functional classification
Loss of Function (LOF)
Most PHKA2 mutations are loss-of-function, reducing PhK activity and causing glycogen storage disease type IXa.
Gain of Function (GOF)
No gain-of-function mutations reported in PHKA2.
Dominant Negative (DN)
No dominant-negative mutations reported; PHKA2 is X-linked and hemizygous in males.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycogen metabolism (Reactome: R-HSA-71387)
• Phosphorylase kinase activation cascade (Reactome: R-HSA-163615)
Protein Summary
The PHKA2 protein is the alpha-2 regulatory subunit of phosphorylase kinase (PhK), a hexadecameric enzyme complex (αβγδ)4. The alpha subunit is tissue-specific; PHKA2 is the liver isoform. It regulates the catalytic gamma subunit in response to calcium and phosphorylation signals. Defects in PHKA2 impair PhK activation, leading to glycogen accumulation in the liver.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHKA2 Knockout HEK293 Cell Line | EDJ-KQ1637 | Human | 5256 | Details Get a Quote |
| PHKA2 Knockout A-549 Cell Line | EDJ-KQ21355 | Human | 5256 | Details Get a Quote |
| PHKA2 Knockout HCT 116 Cell Line | EDJ-KQ21356 | Human | 5256 | Details Get a Quote |
| PHKA2 Knockout HeLa Cell Line | EDJ-KQ21357 | Human | 5256 | Details Get a Quote |
