TCF7L2 Gene - Transcription Factor 7 Like 2
Key regulator of Wnt signaling and type 2 diabetes susceptibility
Gene Information Card
| Symbol | TCF7L2 |
|---|---|
| Full Name | Transcription Factor 7 Like 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q25.2 |
| NCBI Gene ID | 6934 ncbi.nlm.nih.gov/gene/6934 |
| Ensembl ID | ENSG00000148737 |
| UniProt ID | Q9NQB0 |
| OMIM ID | 602228 |
| HGNC ID | 11641 |
| Aliases | TCF4, TCF-4, hTCF-4, TCF7L2 |
Description
TCF7L2 (Transcription Factor 7 Like 2) encodes a high mobility group (HMG) box-containing transcription factor that is a key component of the Wnt/beta-catenin signaling pathway. It acts as a transcriptional repressor or activator depending on its binding partners. Variants in TCF7L2 are strongly associated with type 2 diabetes risk, and the gene is also implicated in colorectal cancer and other malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Intronic variants (e.g., rs7903146) alter enhancer activity and islet gene expression, impairing insulin secretion | GWAS, functional studies (PMID: 16917849, 16917850) |
| Colorectal Cancer | TCF7L2 mutations (e.g., frameshift in exon 17) disrupt beta-catenin/TCF transcriptional regulation, promoting Wnt pathway activation | COSMIC, PMID: 10431240 |
| Maturity-Onset Diabetes of the Young (MODY) | Rare coding variants in TCF7L2 may contribute to monogenic diabetes | ClinVar, PMID: 21723289 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Colon | 15.3 | Medium |
| Small Intestine | 14.8 | Medium |
| Liver | 8.2 | Low |
| Adipose Tissue | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | Cervical cancer cell line |
| HCT116 | 18.5 | Colorectal carcinoma cell line |
| MCF7 | 7.9 | Breast cancer cell line |
| HEK293 | 9.1 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7903146 (C>T) | SNP (intronic) | ~30% in European populations | Associated with increased T2D risk; alters enhancer activity |
| c.1222_1223delAG | Frameshift deletion | <1% in colorectal cancer | Loss of C-terminal domain; dominant-negative effect on Wnt signaling |
| p.Pro19Ala | Missense | Rare | Unknown functional effect; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1222_1223delAG) produce truncated proteins lacking the C-terminal binding domain, impairing transcriptional activation.
Gain of Function (GOF)
Not well characterized; some intronic variants may increase enhancer activity leading to altered gene expression.
Dominant Negative (DN)
Truncated TCF7L2 proteins can interfere with wild-type function by competing for beta-catenin binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Hippo signaling pathway (KEGG: hsa04390)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
Protein Summary
TCF7L2 (also known as TCF4) is a 596-amino acid protein containing an N-terminal beta-catenin binding domain and a C-terminal HMG box DNA-binding domain. It forms a complex with beta-catenin to regulate transcription of Wnt target genes such as MYC and CCND1. The protein is widely expressed, with highest levels in pancreas, colon, and small intestine. Alternative splicing generates multiple isoforms with distinct functional properties.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TCF7L2 Knockout HEK293 Cell Line | EDJ-KQ340 | Human | 6934 | Details Get a Quote |
| TCF7L2 Knockout HeLa Cell Line | EDJ-KQ17974 | Human | 6934 | Details Get a Quote |
| TCF7L2 Knockout A-549 Cell Line | EDJ-KQ18513 | Human | 6934 | Details Get a Quote |
| TCF7L2 Knockout HCT 116 Cell Line | EDJ-KQ18514 | Human | 6934 | Details Get a Quote |
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