CBY1
protein-codingchibby family member 1, beta catenin antagonist
Gene summary
Beta-catenin is a transcriptional activator and oncoprotein involved in the development of several cancers. The protein encoded by this gene interacts directly with the C-terminal region of beta-catenin, inhibiting oncogenic beta-catenin-mediated transcriptional activation by competing with transcription factors for binding to beta-catenin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- C22orf2
- PGEA1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018772
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CBY1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015373.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 7 | 0 | 0 | 9 |
Highest pathogenic variant AF is 0.00001672904
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056188.1 | 4 | MANE Select | |
| Ensembl | ENSP00000216029.3 | 4 | MANE Select | |
| RefSeq | NP_001002880.3 | 4 | Standard | |
| Ensembl | ENSP00000380026.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- WNT-Ncore
- Signaling by WNT
- Signal Transduction
- Deactivation of the beta-catenin transactivating complex
- Wnt Canonical
Biological Process
- protein localization
- negative regulation of Wnt signaling pathway
- fat cell differentiation
- negative regulation of transcription, DNA-templated
- protein homotetramerization
Molecular Function
- protein binding
- beta-catenin binding
- identical protein binding
- protein homodimerization activity
Cellular Component
- nucleus
- nucleoplasm
- trans-Golgi network
- centriole
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396811
- Coding exons
- 4
- Length
- 17219
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125747
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.438 | 69 | 80.0 | 0.862 | 0.00000532 | 810 |
| Missense (PolyPhen) | 14 | 21.834 | 0.64121 | 273 | ||
| Synonymous | 0.348 | 29 | 31.5 | 0.921 | 0.00000186 | 249 |
| Loss of Function | 0.659 | 5 | 6.86 | 0.729 | 3.57e-7 | 76 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors. Has also been shown to play a role in regulating the intracellular trafficking of polycystin-2/PKD2 and possibly of other intracellular proteins. Promotes adipocyte and cardiomyocyte differentiation. {ECO:0000269|PubMed:12712206, ECO:0000269|PubMed:15194699}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.514
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |