TLE2
protein-codingTLE family member 2, transcriptional corepressor, the group of TLE family|WD repeat domain containing|Wnt enhanceosome complex
Gene summary
Enables transcription corepressor activity. Involved in negative regulation of DNA-templated transcription and negative regulation of canonical Wnt signaling pathway. Located in nuclear body. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.0 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 TLE2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003260.5. 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 | 3 | 6 | 9 | |||
| missense | 122 | 4 | 126 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 130 | 10 | 0 | 140 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003251.2 | 20 | MANE Select | |
| Ensembl | ENSP00000262953.5 | 20 | MANE Select | |
| RefSeq | NP_001138233.1 | 19 | Standard | |
| RefSeq | NP_001138234.1 | 16 | 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
- signal transduction
- animal organ morphogenesis
- Wnt signaling pathway
- negative regulation of transcription, DNA-templated
- negative regulation of canonical Wnt signaling pathway
Molecular Function
- transcription corepressor activity
- protein binding
- repressing transcription factor binding
Cellular Component
- extracellular space
- nucleus
- nucleoplasm
- transcription factor complex
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262953
- Coding exons
- 20
- Length
- 49998
- Individuals with no LoFs
- 124757
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 124818
- p
- 0.000244
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.830 | 405 | 455 | 0.891 | 0.0000292 | 4718 |
| Missense (PolyPhen) | 125 | 157.82 | 0.79205 | 1604 | ||
| Synonymous | -1.35 | 241 | 216 | 1.12 | 0.0000167 | 1504 |
| Loss of Function | 3.13 | 18 | 39.2 | 0.460 | 0.00000185 | 432 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000067 | 0.000064 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.00035 | 0.00032 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00017 | 0.00016 | rare |
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
- 0.126
Intolerance Scores
- LoFtool
- 0.951
- RVIS EVS
- -1.13
- RVIS percentile EVS
- 6.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |