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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CBY1
chibby 1, beta catenin antagonist
Chromosome 22 Β· 22q13.1
NCBI Gene: 25776Ensembl: ENSG00000100211.13HGNC: HGNC:1307UniProt: Q9Y3M2
60PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
trans-Golgi networkbeta-catenin bindingidentical protein bindingprotein homodimerization activityJoubert syndromecerebellar ataxiapolydactylyMolar tooth sign on MRI
✦AI Summary

CBY1 encodes a small coiled-coil protein that functions as a dual regulator of Wnt signaling and ciliogenesis. As a beta-catenin antagonist, CBY1 inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and competing with TCF/LEF transcription factors for beta-catenin-mediated transcriptional activation 1. In ciliogenesis, CBY1 localizes to centrioles/basal bodies and plays a crucial role in primary cilium formation and function 23. The protein facilitates basal body docking to the plasma membrane through recruitment of small vesicles and interacts with FAM92 proteins containing BAR domains to promote membrane remodeling processes essential for ciliogenesis 24. CBY1 dysfunction is associated with multiple diseases. Biallelic loss-of-function variants cause a ciliopathy characterized by features of Joubert syndrome, including developmental delay, cerebellar ataxia, and the pathognomonic molar tooth sign 3. In chr22 myeloid leukemia, CBY1 down-regulation contributes to aberrant beta-catenin activation in leukemic stem cells 5. Additionally, CBY1 variants have been implicated in mitral valve prolapse through dysregulation of beta-catenin signaling during cardiac development 1. The protein's dual function makes it critical for both developmental processes and disease pathogenesis.

Sources cited
1
CBY1 inhibits Wnt signaling by binding beta-catenin and competing with TCF/LEF transcription factors; mutations cause mitral valve prolapse
PMID: 33811421
2
CBY1 localizes to centrioles/basal bodies and facilitates ciliogenesis through vesicle recruitment and interaction with FAM92 proteins
PMID: 27528616
3
Biallelic CBY1 loss-of-function variants cause ciliopathy with Joubert syndrome features
PMID: 33131181
4
CBY1 down-regulation in chronic myeloid leukemia contributes to aberrant beta-catenin activation
PMID: 26147002
5
CBY1 interacts with FAM92A BAR domain to regulate membrane remodeling in ciliogenesis
PMID: 40484380
Disease Associationsβ“˜20
Joubert syndromeOpen Targets
0.61Moderate
cerebellar ataxiaOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.46Moderate
Molar tooth sign on MRIOpen Targets
0.46Moderate
polydactylyOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.17Weak
hypothyroidismOpen Targets
0.13Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
autoimmune diseaseOpen Targets
0.10Weak
ovulationOpen Targets
0.10Suggestive
cholelithiasisOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.08Suggestive
chronic myelogenous leukemiaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.07Suggestive
coronary atherosclerosisOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
gallstonesOpen Targets
0.07Suggestive
Hashimoto's thyroiditisOpen Targets
0.07Suggestive
Pathogenic Variants2
NM_015373.4(CBY1):c.189_190del (p.Gly64_Val65insTer)Pathogenic
Joubert syndrome
β˜†β˜†β˜†β˜†2020β†’ Residue 64
NM_015373.4(CBY1):c.64_65dup (p.Asn23fs)Pathogenic
Joubert syndrome
β˜†β˜†β˜†β˜†2018β†’ Residue 23
View on ClinVar β†—
Related Genes
CTNNB1Protein interaction100%XPO1Protein interaction99%YWHAZProtein interaction99%CIBAR1Protein interaction95%DZIP1LProtein interaction77%PKD2Protein interaction76%
Tissue Expression6 tissues
Heart
100%
Ovary
90%
Liver
62%
Brain
60%
Lung
44%
Bone Marrow
16%
Gene Interaction Network
Click a node to explore
CBY1CTNNB1XPO1YWHAZCIBAR1DZIP1LPKD2
PROTEIN STRUCTURE
Preparing viewer…
PDB4WRQ Β· 2.41 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.14LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.58 [0.32–1.14]
RankingsWhere CBY1 stands among ~20K protein-coding genes
  • #7,637of 20,598
    Most Researched60
  • #4,405of 5,498
    Most Pathogenic Variants2
  • #11,813of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedCBY1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Chibby1 knockdown promotes mesenchymal-to-epithelial transition-like changes.
PMID: 28107095
Cell Cycle Β· 2017
1.00
2
BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis.
PMID: 27528616
Mol Cell Biol Β· 2016
0.90
3
Dimerization of the BAR domain-containing protein FAM92A modulates lipid binding and interaction with CBY1.
PMID: 40484380
J Biol Chem Β· 2025
0.80
4
DZIP1 regulates mammalian cardiac valve development through a Cby1-Ξ²-catenin mechanism.
PMID: 33811421
Dev Dyn Β· 2021
0.70
5
Observational, causal relationship and shared genetic basis between cholelithiasis and gastroesophageal reflux disease: evidence from a cohort study and comprehensive genetic analysis.
PMID: 40139907
Gigascience Β· 2025
0.60