TLE4
protein-codingTLE family member 4, transcriptional corepressor, the group of TLE family|WD repeat domain containing|Wnt enhanceosome complex
Gene summary
Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~155.1 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 TLE4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007005.6. 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 | 5 | 9 | |||
| missense | 57 | 1 | 58 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 67 | 1 | 5 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008936.2 | 20 | MANE Select | |
| Ensembl | ENSP00000365735.2 | 20 | MANE Select | |
| RefSeq | NP_001269677.1 | 21 | Standard | |
| RefSeq | NP_001269678.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Degradation of beta-catenin by the destruction complex
- Signaling by WNT
- Signal Transduction
- Repression of WNT target genes
- Notch
Biological Process
- negative regulation of transcription by RNA polymerase II
- biological_process
- Wnt signaling pathway
- negative regulation of canonical Wnt signaling pathway
- beta-catenin-TCF complex assembly
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- molecular_function
- chromatin binding
- transcription corepressor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- beta-catenin-TCF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376552
- Coding exons
- 20
- Length
- 154971
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125725
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.60 | 246 | 464 | 0.530 | 0.0000261 | 5061 |
| Missense (PolyPhen) | 70 | 183.65 | 0.38116 | 2074 | ||
| Synonymous | -0.164 | 187 | 184 | 1.02 | 0.0000117 | 1537 |
| Loss of Function | 5.73 | 2 | 42.1 | 0.0475 | 0.00000214 | 474 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| 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 PAX5, and 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. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.236
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |