CSNK2A1 Gene

CSNK2A1 Gene

<div class="infobox infobox-gene">
<h3>CSNK2A1</h3>
<table>
<tr><th>Full Name</th><td>Casein Kinase 2 Alpha 1</td></tr>
<tr><th>Gene Symbol</th><td>CSNK2A1</td></tr>
<tr><th>Chromosome</th><td>20p13</td></tr>
<tr><th>NCBI Gene ID</th><td>[1457](https://www.ncbi.nlm.nih.gov/gene/1457)</td></tr>
<tr><th>OMIM</th><td>[115440](https://omim.org/entry/115440)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000101266](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101266)</td></tr>
<tr><th>UniProt</th><td>[P68400](https://www.uniprot.org/uniprot/P68400)</td></tr>
<tr><th>Encoded Protein</th><td>[CK2α protein](/proteins/ck2-alpha-protein)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's disease, Parkinson's disease, Cancer, Okur-Chung syndrome</td></tr>
</table>
</div>

Overview

CSNK2A1 Gene

<div class="infobox infobox-gene">
<h3>CSNK2A1</h3>
<table>
<tr><th>Full Name</th><td>Casein Kinase 2 Alpha 1</td></tr>
<tr><th>Gene Symbol</th><td>CSNK2A1</td></tr>
<tr><th>Chromosome</th><td>20p13</td></tr>
<tr><th>NCBI Gene ID</th><td>[1457](https://www.ncbi.nlm.nih.gov/gene/1457)</td></tr>
<tr><th>OMIM</th><td>[115440](https://omim.org/entry/115440)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000101266](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101266)</td></tr>
<tr><th>UniProt</th><td>[P68400](https://www.uniprot.org/uniprot/P68400)</td></tr>
<tr><th>Encoded Protein</th><td>[CK2α protein](/proteins/ck2-alpha-protein)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's disease, Parkinson's disease, Cancer, Okur-Chung syndrome</td></tr>
</table>
</div>

Overview

CSNK2A1 (Casein Kinase 2 Alpha 1) encodes the catalytic alpha subunit of casein kinase 2 (CK2), a constitutively active serine/threonine kinase with over 300 known substrates.[@stahl2021] CK2 plays critical roles in [tau](/proteins/tau) phosphorylation, NMDA receptor modulation, neuroinflammation, and neuronal survival pathways.[@lebrin2005] 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.

Gene Structure and Expression

The CSNK2A1 gene spans approximately 56 kb on chromosome 20p13 and contains 10 exons.[@wirkner1994] The encoded 350-amino acid protein forms the catalytic subunit that:

• Heterotetramer formation: Combines with regulatory β subunits (CSNK2B) to form α₂β₂ or αα'β₂ holoenzymes
• Constitutive activity: Unlike most kinases, CK2 is constitutively active without requiring phosphorylation
• Ubiquitous expression: High levels in brain, particularly in [neurons](/entities/neurons)

Function

CK2 Holoenzyme

CK2 exists as a heterotetramer (α₂β₂ or αα'β₂) with multiple functions:[@litchfield2003]

Tau Phosphorylation

CK2 phosphorylates tau at multiple sites:[@plotner2017]

• Ser202/Thr205: AT8 epitope (also GSK3β, [CDK5](/proteins/cdk5) targets)
• Ser396/Ser404: PHF-1 epitope
• Ser422: Disease-associated site
• Priming activity: CK2 can prime tau for subsequent GSK3β phosphorylation

NMDA Receptor Modulation

CK2 phosphorylates NMDA receptor subunits:[@lieberman1999]

• NR2B (GRIN2B): Ser1480 phosphorylation enhances channel function
• NR2A (GRIN2A): Modulates synaptic localization
• NMDA-mediated toxicity: CK2 inhibition reduces excitotoxicity

Neuroinflammation

CK2 regulates inflammatory signaling:[@ahmad2008]

• [NF-κB](/entities/nf-kb) pathway: Phosphorylates IκBα, promoting degradation
• TNF-α signaling: Modulates TNFR1 responses
• Microglial activation: CK2 activity increases in activated [microglia](/cell-types/microglia-neuroinflammation)

Disease Associations

Alzheimer's Disease

CK2 shows complex involvement in AD:[@rosenberger2016]

• Elevated activity: Increased CK2 activity in AD brains
• Tau pathology: CK2 phosphorylates tau at disease-relevant sites
• [Aβ](/proteins/amyloid-beta) interactions: CK2 phosphorylation affects [APP](/entities/app-protein) processing
• Neuroprotection: CK2 also activates survival pathways (AKT, NF-κB)

Parkinson's Disease

CK2 contributes to PD pathology:[@inglis2009]

• [α-synuclein](/proteins/alpha-synuclein) phosphorylation: CK2 phosphorylates Ser129
• Dopaminergic neuron vulnerability: CK2 inhibition reduces neuronal loss in models
• DJ-1 regulation: CK2 phosphorylates DJ-1, affecting its protective function

Okur-Chung Syndrome

De novo CSNK2A1 variants cause:[@okur2019]

• Neurodevelopmental disorder: Intellectual disability, developmental delay
• Features: Microcephaly, facial dysmorphism, skeletal anomalies
• Mechanism: Haploinsufficiency or dominant-negative effects

Expression Profile

| 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](/entities/astrocytes) | Moderate | Inflammatory signaling |

Common Variants

| 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 |

Therapeutic Implications

CK2 Inhibitors for Neurodegeneration

CK2 inhibition as therapeutic strategy:[@chon2022]

Challenges

• Dual role: CK2 has both neurotoxic and neuroprotective functions
• Ubiquitous expression: Systemic inhibition affects many tissues
• Constitutive activity: Difficult to modulate physiologically
• [Blood-brain barrier](/entities/blood-brain-barrier): Need CNS-penetrant compounds

See Also

• [CSNK2A2 Gene](/genes/csnk2a2)
• [CSNK2B Gene](/genes/csnk2b)
• [Tau Pathology](/mechanisms/tau-pathology)
• [NMDA Receptor](/entities/nmda-receptor)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [GeneCards: CSNK2A1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSNK2A1)
• [UniProt: P68400](https://www.uniprot.org/uniprot/P68400)
• [NCBI Gene: 1457](https://www.ncbi.nlm.nih.gov/gene/1457)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CSNK2A1 Gene discovered through SciDEX knowledge graph analysis: