TLE3
protein-codingTLE family member 3, transcriptional corepressor, the group of WD repeat domain containing|Wnt enhanceosome complex|TLE family|MicroRNA protein coding host genes
Gene summary
This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TLE3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001105192.3. 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 | 4 | 3 | 4 | 11 | ||
| missense | 68 | 1 | 69 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 76 | 4 | 4 | 84 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001098662.1 | 20 | MANE Select | |
| Ensembl | ENSP00000394717.3 | 20 | MANE Select | |
| RefSeq | NP_001269908.1 | 20 | Standard | |
| RefSeq | NP_001269909.1 | 20 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tle3a | Danio rerio | Structure: neural tube Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- White fat cell differentiation
- White fat cell differentiation
- Degradation of beta-catenin by the destruction complex
- Signaling by WNT
- Signal Transduction
Biological Process
- regulation of transcription, DNA-templated
- signal transduction
- animal organ morphogenesis
- Wnt signaling pathway
- negative regulation of canonical Wnt signaling pathway
Molecular Function
- transcription corepressor activity
- protein binding
- repressing transcription factor binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- beta-catenin-TCF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000558939
- Coding exons
- 20
- Length
- 50387
- Individuals with no LoFs
- 122336
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 122337
- p
- 0.00000409
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.72 | 246 | 474 | 0.519 | 0.0000287 | 5030 |
| Missense (PolyPhen) | 78 | 239.06 | 0.32628 | 2635 | ||
| Synonymous | -1.08 | 225 | 205 | 1.10 | 0.0000150 | 1496 |
| Loss of Function | 5.91 | 0 | 40.7 | 0.00 | 0.00000219 | 445 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000091 | 0.0000091 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.864
- RVIS EVS
- -1.02
- RVIS percentile EVS
- 8
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.976
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |