CSNK1A1: Casein Kinase 1 Alpha 1
A key regulator of Wnt signaling, cell cycle, and DNA damage response, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | CSNK1A1 |
|---|---|
| Full Name | Casein Kinase 1 Alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 1452 ncbi.nlm.nih.gov/gene/1452 |
| Ensembl ID | ENSG00000113712 |
| UniProt ID | P48729 |
| OMIM ID | 600505 |
| HGNC ID | 2451 |
| Aliases | CK1, CK1a, CKIa, PRO2975 |
Description
CSNK1A1 encodes casein kinase 1 alpha 1 (CK1α), a serine/threonine protein kinase that phosphorylates a wide range of substrates. It is a critical negative regulator of the Wnt/β-catenin signaling pathway by phosphorylating β-catenin, targeting it for degradation. CK1α also plays roles in cell cycle regulation, DNA damage repair, and circadian rhythm. Mutations and altered expression of CSNK1A1 are associated with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic Syndrome (MDS) | Loss-of-function mutations in CSNK1A1 lead to activation of Wnt/β-catenin signaling, promoting hematopoietic stem cell proliferation and impaired differentiation. | COSMIC, ClinVar |
| Acute Myeloid Leukemia (AML) | Somatic mutations (e.g., missense, frameshift) in CSNK1A1 are recurrent in AML, contributing to leukemogenesis via dysregulated β-catenin and p53 pathways. | COSMIC, ClinVar |
| Colorectal Cancer | CSNK1A1 overexpression or mutation can alter Wnt signaling and cell cycle control, though direct evidence is limited. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.8 | Medium |
| Spleen | 9.2 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| HEK 293 (embryonic kidney) | 12.8 | Medium expression |
| HeLa (cervical cancer) | 11.5 | Medium expression |
| MCF7 (breast cancer) | 9.7 | Medium expression |
| A549 (lung cancer) | 8.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.433C>T (p.Arg145*) | Nonsense | <1% | Loss of function; truncation of kinase domain |
| c.488_489del (p.Glu163fs) | Frameshift | <1% | Loss of function; premature stop codon |
| c.617G>A (p.Arg206His) | Missense | <1% | Likely loss of function; reduced kinase activity |
| c.832C>T (p.Arg278Trp) | Missense | <1% | Unknown; located in C-terminal regulatory domain |
Mutation functional classification
Loss of Function (LOF)
Recurrent nonsense and frameshift mutations in MDS/AML result in truncated or unstable protein, leading to loss of kinase activity and Wnt pathway activation.
Gain of Function (GOF)
Not well documented; some missense variants may increase kinase activity but evidence is limited.
Dominant Negative (DN)
Not reported for CSNK1A1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Cell Cycle
• Mitotic (Reactome: R-HSA-69278)
• DNA Damage/Telomere Stress Induced Senescence (Reactome: R-HSA-2559580)
Protein Summary
Casein kinase 1 alpha 1 (CK1α) is a 337-amino acid protein with a conserved N-terminal kinase domain and a C-terminal regulatory domain. It phosphorylates substrates on serine/threonine residues, requiring priming phosphorylation or a specific consensus sequence (pS/pT-X-X-S/T). CK1α is a key component of the β-catenin destruction complex, where it phosphorylates β-catenin at Ser45, priming it for subsequent phosphorylation by GSK3β and ubiquitin-mediated degradation. Beyond Wnt signaling, CK1α regulates p53, MDM2, and circadian clock proteins. Its activity is modulated by autophosphorylation and interaction with regulatory proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSNK1A1L Knockout HEK293 Cell Line | EDJ-KQ288 | Human | 122011 | Details Get a Quote |
| CSNK1A1L Knockout HeLa Cell Line | EDJ-KQ58092 | Human | 122011 | Details Get a Quote |
| CSNK1A1L Knockout A-549 Cell Line | EDJ-KQ66580 | Human | 122011 | Details Get a Quote |
| CSNK1A1L Knockout HCT 116 Cell Line | EDJ-KQ74995 | Human | 122011 | Details Get a Quote |
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