| Full Name | Casein Kinase 2 Alpha 1 |
|---|---|
| Gene Symbol | CSNK2A1 |
| Chromosome | 20p13 |
| NCBI Gene ID | [1457](https://www.ncbi.nlm.nih.gov/gene/1457) |
| OMIM | [115440](https://omim.org/entry/115440) |
| Ensembl | [ENSG00000101266](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101266) |
| UniProt | [P68400](https://www.uniprot.org/uniprot/P68400) |
| Encoded Protein | [CK2α protein](/proteins/ck2-alpha-protein) |
| Associated Diseases | Alzheimer's disease, Parkinson's disease, Cancer, Okur-Chung syndrome |
CSNK2A1 (Casein Kinase 2 Alpha 1) encodes the catalytic α subunit of casein kinase 2 (CK2), a constitutively active serine/threonine kinase with over 300 known substrates.[1] CK2 plays critical roles in tau phosphorylation, NMDA receptor modulation, neuroinflammation, and neuronal survival pathways.[2] In neurodegeneration, CK2 hyperactivity contributes to pathological tau phosphorylation while also providing neuroprotection through anti-apoptotic signaling, creating a complex dual role in disease pathogenesis.
The CSNK2A1 gene spans approximately 56 kb on chromosome 20p13 and contains 10 exons.[3] The encoded 350-amino acid protein forms the catalytic subunit that:
Expression in the nervous system: CK2α is highly expressed in hippocampus, cortex, and cerebellum. Activity increases in AD brains, correlating with neurofibrillary tangle burden.[4]
CK2 exists as a heterotetramer (α₂β₂ or αα'β₂) with multiple functions:[5]
CK2 phosphorylates tau at multiple sites:[6]
CK2 phosphorylates NMDA receptor subunits:[7]
CK2 regulates inflammatory signaling:[8]
CK2 shows complex involvement in AD:[9]
CK2 contributes to PD pathology:[10]
De novo CSNK2A1 variants cause:[11]
| Tissue | Expression Level | Notes |
|---|---|---|
| Hippocampus | High | Tau phosphorylation, memory |
| Cerebral cortex | High | NMDA receptor regulation |
| Cerebellum | Moderate | Motor coordination |
| Microglia | Moderate | Increases with activation |
| Astrocytes | Moderate | Inflammatory signaling |
| Variant | dbSNP | Effect | Clinical Relevance |
|---|---|---|---|
| rs1008818 | NCBI | 3' UTR | Associated with AD risk in some cohorts |
| rs11552449 | NCBI | Intronic | Parkinson's disease association |
| rs2072554 | NCBI | Intronic | Cancer risk modifier |
CK2 inhibition as therapeutic strategy:[12]
Stahl M, et al. CK2: a protein kinase with a rich substrate repertoire. Cell Mol Life Sci. 2021. ↩︎
Lebrin F, et al. CK2 and its role in neurodegenerative disease. Prog Brain Res. 2005. ↩︎
Wirkner U, et al. The gene encoding casein kinase II subunit alpha. Genomics. 1994. ↩︎
Iimoto DS, et al. Casein kinase II in Alzheimer's disease. J Neurochem. 1990. ↩︎
Litchfield DW. Protein kinase CK2: structure, regulation and role in cellular decisions. Biochem Cell Biol. 2003. ↩︎
Plotner B, et al. Phosphorylation of the microtubule-associated protein tau by CK2. J Biol Chem. 2017. ↩︎
Lieberman DN, Mody I. CK2 modulation of NMDA receptors. J Neurophysiol. 1999. ↩︎
Ahmad KA, et al. CK2 and NF-κB signaling in cancer and inflammation. Oncogene. 2008. ↩︎
Rosenberger AFN, et al. CK2 in Alzheimer's disease pathology. Acta Neuropathol. 2016. ↩︎
Inglis KJ, et al. CK2 phosphorylation of α-synuclein. J Neurosci. 2009. ↩︎
Okur V, et al. CSNK2A1 variants cause Okur-Chung neurodevelopmental syndrome. Am J Hum Genet. 2019. ↩︎
Chon HJ, et al. CK2 inhibitors in cancer therapy. Cancers (Basel). 2022. ↩︎