CBY1: A Key Regulator of Ciliogenesis and Wnt Signaling
Comprehensive genomic and functional analysis of the CBY1 gene, its role in primary cilia formation, and associated diseases.
Gene Information Card
| Symbol | CBY1 |
|---|---|
| Full Name | Chibby family member 1, beta-catenin antagonist |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 25776 ncbi.nlm.nih.gov/gene/25776 |
| Ensembl ID | ENSG00000100220 |
| UniProt ID | Q9Y3M2 |
| OMIM ID | 608575 |
| HGNC ID | 21287 |
| Aliases | CBY, ARG1, HS-CBY, PIGEA-14 |
Description
CBY1 (Chibby family member 1) encodes a conserved protein that localizes to the base of primary cilia and acts as a negative regulator of beta-catenin-mediated Wnt signaling. It is essential for ciliogenesis, interacting with components of the ciliary transition zone and the intraflagellar transport machinery. CBY1 is widely expressed and its dysfunction is linked to ciliopathies and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ciliopathy (e.g., Joubert syndrome-related disorders) | Loss of CBY1 disrupts ciliary assembly and signaling, leading to developmental defects. | OMIM #608575; PMID: 19004860 |
| Colorectal cancer | CBY1 downregulation or mislocalization may enhance beta-catenin activity, promoting tumorigenesis. | PMID: 19004860; PMID: 22194698 |
| Breast cancer | Reduced CBY1 expression correlates with poor prognosis and increased Wnt signaling. | PMID: 22194698 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Kidney | 6.7 | Low |
| Liver | 4.2 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression; used in functional studies |
| HeLa | 9.8 | Moderate expression |
| MCF7 | 6.5 | Low expression; breast cancer line |
| HepG2 | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Likely loss of start codon; predicted loss of function |
| c.100C>T (p.Arg34Trp) | Missense | 0.01% (gnomAD) | May affect protein stability; uncertain significance |
| c.250_251del (p.Leu84fs) | Frameshift | Very rare | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the start codon lead to loss of CBY1 function, impairing ciliogenesis and Wnt inhibition.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CBY1.
Dominant Negative (DN)
No evidence for dominant-negative effects; CBY1 mutations are typically recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Cilium assembly (Reactome: R-HSA-5617833)
Protein Summary
CBY1 is a 126-amino acid protein that localizes to the base of primary cilia. It contains a conserved N-terminal domain that binds beta-catenin, inhibiting Wnt signaling. CBY1 also interacts with ciliary proteins such as CEP290 and NPHP1, facilitating ciliogenesis. Its structure includes a coiled-coil region and a nuclear localization signal.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CBY1 Knockout HEK293 Cell Line | EDJ-KQ3853 | Human | 25776 | Details Get a Quote |
| CBY1 Knockout A-549 Cell Line | EDJ-KQ26040 | Human | 25776 | Details Get a Quote |
| CBY1 Knockout HCT 116 Cell Line | EDJ-KQ26041 | Human | 25776 | Details Get a Quote |
| CBY1 Knockout HeLa Cell Line | EDJ-KQ24681 | Human | 25776 | Details Get a Quote |
