TCF7L1: Transcription Factor 7 Like 1
A key regulator of Wnt signaling and stem cell differentiation
Gene Information Card
| Symbol | TCF7L1 |
|---|---|
| Full Name | Transcription Factor 7 Like 1 (T-Cell Specific, HMG-Box) |
| Gene Type | Protein coding |
| Chromosomal Location | 2p11.2 |
| NCBI Gene ID | 83439 ncbi.nlm.nih.gov/gene/83439 |
| Ensembl ID | ENSG00000152284 |
| UniProt ID | Q9HCS4 |
| OMIM ID | 604652 |
| HGNC ID | 11639 |
| Aliases | TCF3, HMG box transcription factor 3, TCF-3, bHLHb21 |
Description
TCF7L1 (Transcription Factor 7 Like 1) encodes a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of high mobility group (HMG) box transcription factors. It acts as a downstream effector of the canonical Wnt signaling pathway, repressing target gene expression in the absence of Wnt signals and activating transcription upon β-catenin binding. TCF7L1 is critical for embryonic development, stem cell maintenance, and differentiation, and its dysregulation is implicated in several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | TCF7L1 mutations or altered expression disrupt Wnt/β-catenin transcriptional regulation, promoting uncontrolled cell proliferation | COSMIC, ClinVar |
| Breast cancer | TCF7L1 overexpression correlates with poor prognosis; modulates epithelial-mesenchymal transition | NCBI Gene, PubMed |
| Gastric cancer | TCF7L1 downregulation linked to tumor progression via Wnt pathway activation | COSMIC, PubMed |
| Developmental disorders | Germline variants in TCF7L1 associated with intellectual disability and craniofacial abnormalities | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Colon | 8.3 | Low |
| Breast | 6.1 | Low |
| Stomach | 5.4 | Low |
| Testis | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney; high expression |
| HCT 116 | 9.8 | Colorectal carcinoma; moderate expression |
| MCF7 | 7.2 | Breast cancer; moderate expression |
| K562 | 3.1 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | <0.1% | Altered DNA binding; loss of repressor function |
| c.1450_1451del (p.Leu484fs) | Frameshift | <0.1% | Truncated protein; loss of function |
| c.782G>A (p.Arg261His) | Missense | <0.1% | Reduced β-catenin interaction; dominant negative effect |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the HMG box or β-catenin binding domain, impairing transcriptional repression.
Gain of Function (GOF)
Not commonly reported; most mutations lead to loss of repressor activity.
Dominant Negative (DN)
Missense mutations in the β-catenin interaction domain (e.g., p.Arg261His) that disrupt normal TCF/β-catenin complex formation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• TCF/LEF signaling (KEGG: hsa04310)
• Transcriptional regulation by TCF/LEF (Reactome: R-HSA-201681)
Protein Summary
TCF7L1 is a 588-amino acid protein containing an N-terminal β-catenin binding domain and a C-terminal HMG box that mediates sequence-specific DNA binding. It functions primarily as a transcriptional repressor in the absence of Wnt signaling, recruiting co-repressors such as Groucho/TLE. Upon Wnt activation, β-catenin displaces co-repressors and converts TCF7L1 into an activator. The protein is widely expressed in embryonic and adult tissues, with highest levels in the brain and colon.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TCF7L1 Knockout HEK293 Cell Line | EDJ-KQ339 | Human | 83439 | Details Get a Quote |
| TCF7L1 Knockout A-549 Cell Line | EDJ-KQ18511 | Human | 83439 | Details Get a Quote |
| TCF7L1 Knockout HCT 116 Cell Line | EDJ-KQ18512 | Human | 83439 | Details Get a Quote |
| TCF7L1 Knockout HeLa Cell Line | EDJ-KQ57434 | Human | 83439 | Details Get a Quote |
