TLE4: A Corepressor in Transcriptional Regulation and Development
TLE4 (Transducin-Like Enhancer of Split 4) is a transcriptional corepressor involved in Notch signaling, hematopoiesis, and neurogenesis, with implications in leukemia and other cancers.
Gene Information Card
| Symbol | TLE4 |
|---|---|
| Full Name | Transducin-Like Enhancer of Split 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.31 |
| NCBI Gene ID | 7091 ncbi.nlm.nih.gov/gene/7091 |
| Ensembl ID | ENSG00000106829 |
| UniProt ID | Q04727 |
| OMIM ID | 605132 |
| HGNC ID | 11839 |
| Aliases | ESG, GRG4, BCE-1 |
Description
TLE4 encodes a member of the TLE (transducin-like enhancer of split) family of transcriptional corepressors. These proteins are homologs of the Drosophila Groucho protein and function by interacting with transcription factors such as HES, RUNX1, and LEF1 to repress transcription. TLE4 plays critical roles in Notch, Wnt, and other signaling pathways, influencing cell fate decisions during hematopoiesis, neurogenesis, and somitogenesis. It is frequently deleted or mutated in acute myeloid leukemia (AML) and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | TLE4 deletions or loss-of-function mutations impair transcriptional repression of RUNX1 target genes, promoting leukemogenesis. | PMID: 15122513; COSMIC |
| Myelodysplastic Syndromes (MDS) | Deletions at 9q21.31 involving TLE4 are recurrent in MDS, suggesting a tumor suppressor role. | PMID: 17289855; ClinVar |
| Colorectal Cancer | TLE4 downregulation may contribute to Wnt pathway activation and tumor progression. | PMID: 19029981 |
| Neurodevelopmental Disorders | Rare TLE4 variants have been associated with intellectual disability and autism spectrum disorder. | PMID: 27545680 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Bone Marrow | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Testis | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 10.2 | Myelogenous leukemia line |
| HEK 293 (embryonic kidney) | 7.5 | High expression |
| HeLa (cervical cancer) | 6.0 | Moderate expression |
| HepG2 (liver cancer) | 4.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358*) | Nonsense | <1% | Loss of function; truncation of C-terminal domain |
| c.1450_1454del (p.Glu484fs) | Frameshift | <1% | Loss of function; premature termination |
| c.1A>G (p.Met1?) | Start loss | <1% | Loss of function; no protein produced |
| Deletion of 9q21.31 | Copy number loss | ~5% in AML | Haploinsufficiency; reduced TLE4 expression |
Mutation functional classification
Loss of Function (LOF)
Most TLE4 mutations in AML and MDS are loss-of-function, including nonsense, frameshift, and deletions, leading to reduced corepressor activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TLE4.
Dominant Negative (DN)
Truncated TLE4 proteins lacking the C-terminal domain may act as dominant-negative inhibitors of wild-type TLE proteins, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Wnt signaling pathway (KEGG: hsa04310)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
• RUNX1-regulated transcription (Reactome: R-HSA-8878171)
Protein Summary
TLE4 is a 770-amino-acid nuclear protein containing an N-terminal glutamine-rich domain (Q domain) involved in tetramerization, a glycine/proline-rich region, a CcN motif for nuclear localization, and a C-terminal WD40 repeat domain that mediates protein-protein interactions. It functions as a transcriptional corepressor by recruiting histone deacetylases (HDACs) to target gene promoters. TLE4 is widely expressed, with highest levels in brain and hematopoietic tissues. Its loss contributes to aberrant gene expression in leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TLE4 Knockout HEK293 Cell Line | EDJ-KQ344 | Human | 7091 | Details Get a Quote |
| TLE4 Knockout A-549 Cell Line | EDJ-KQ18524 | Human | 7091 | Details Get a Quote |
| TLE4 Knockout HeLa Cell Line | EDJ-KQ18525 | Human | 7091 | Details Get a Quote |
| TLE4 Knockout HCT 116 Cell Line | EDJ-KQ71618 | Human | 7091 | Details Get a Quote |
