PHKA1 Gene - Phosphorylase Kinase Regulatory Subunit Alpha 1
Genetic and functional insights into PHKA1, a key regulator of glycogen metabolism and its role in glycogen storage disease type IXd.
Gene Information Card
| Symbol | PHKA1 |
|---|---|
| Full Name | Phosphorylase Kinase Regulatory Subunit Alpha 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 5255 ncbi.nlm.nih.gov/gene/5255 |
| Ensembl ID | ENSG00000167123 |
| UniProt ID | P46020 |
| OMIM ID | 311870 |
| HGNC ID | 8925 |
| Aliases | PHKA, PHK-A, MGC138509, MGC142047 |
Description
PHKA1 encodes the alpha-1 regulatory subunit of phosphorylase kinase (PhK), a key enzyme in glycogen metabolism. PhK activates glycogen phosphorylase, which catalyzes the rate-limiting step of glycogenolysis. Mutations in PHKA1 cause X-linked glycogen storage disease type IXd (GSD IXd), characterized by exercise intolerance, muscle weakness, and myopathy. The gene is predominantly expressed in skeletal muscle and heart.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease type IXd (GSD IXd) | Loss-of-function mutations in PHKA1 impair PhK activity, reducing glycogen phosphorylase activation and leading to glycogen accumulation in muscle. | ClinVar, OMIM #311870 |
| X-linked myopathy with excessive autophagy (XMEA) | Rarely reported; PHKA1 variants may contribute to autophagic vacuolar myopathy through disrupted glycogen metabolism. | ClinVar, PubMed (limited evidence) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 38.2 | High |
| Heart | 22.1 | Medium |
| Liver | 1.5 | Low |
| Brain | 0.8 | Low |
| Kidney | 0.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myoblasts | 42.5 | High expression |
| Cardiomyocytes | 25.3 | Medium expression |
| HepG2 | 1.2 | Low expression |
| SH-SY5Y | 0.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.361C>T (p.Arg121*) | Nonsense | <0.01% | Loss of function; premature truncation of alpha subunit |
| c.1192G>A (p.Gly398Arg) | Missense | <0.01% | Loss of function; impaired PhK complex assembly |
| c.1685_1686del (p.Leu562Profs*13) | Frameshift | <0.01% | Loss of function; truncated protein |
| c.2410C>T (p.Arg804Cys) | Missense | <0.01% | Loss of function; reduced catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Majority of PHKA1 mutations are loss-of-function, leading to reduced or absent PhK activity and glycogen accumulation in muscle.
Gain of Function (GOF)
No gain-of-function mutations reported in PHKA1.
Dominant Negative (DN)
No dominant-negative mutations reported; PHKA1 is X-linked and recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycogen metabolism (Reactome: R-HSA-71387)
• Phosphorylase kinase activation cascade (Reactome: R-HSA-163615)
• Metabolism of carbohydrates (Reactome: R-HSA-71336)
Protein Summary
The PHKA1 protein (alpha-1 subunit of phosphorylase kinase) is a 1237-amino acid regulatory subunit that forms part of the hexadecameric PhK complex (alpha4-beta4-gamma4-delta4). It binds calcium ions and calmodulin, modulating the activity of the catalytic gamma subunit. In muscle, PhK phosphorylates and activates glycogen phosphorylase, initiating glycogen breakdown. Defects in PHKA1 disrupt this cascade, causing glycogen storage disease type IXd.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHKA1 Knockout HEK293 Cell Line | EDJ-KQ986 | Human | 5255 | Details Get a Quote |
| PHKA1 Knockout A-549 Cell Line | EDJ-KQ21358 | Human | 5255 | Details Get a Quote |
| PHKA1 Knockout HCT 116 Cell Line | EDJ-KQ21360 | Human | 5255 | Details Get a Quote |
| PHKA1 Knockout HeLa Cell Line | EDJ-KQ21361 | Human | 5255 | Details Get a Quote |
