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TCF7L2 (Transcription factor 7-like 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Prostate cancer and 3 more.
Participates in the Wnt signalling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as a repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1.
Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes affected pathway 0.58, literature 0.97, genetic association 0.72, somatic mutation 0.96, animal model 0.49). IntOGen calls it a driver in 7 cohorts (0 activating, 7 loss-of-function), covering Colon Adenocarcinoma, Colorectal Adenocarcinoma, Hepatocellular Carcinoma, Rectal Adenocarcinoma.
In plain words · TCF7L2 (Transcription factor 7-like 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Prostate cancer and 3 more.
TCF7L2 (Transcription factor 7-like 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Prostate cancer and 3 more.
Participates in the Wnt signalling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as a repressor in the absence of CTNNB1, and as activator in its presence.
No product in this corpus aims at TCF7L2 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1997. Earliest sequence paper UniProt cites for the protein: Korinek et al, Science, 1997, "Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma". Source.
Sources: HGNC HGNC:11641 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9NQB0 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000148737 (association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: colorectal cancer 0.76, prostate cancer 0.60, skin cancer 0.52, breast cancer 0.65 (GraphQL API, CC0)); IntOGen TCF7L2 (driver in 7 cohorts (Act 0, LoF 7); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Participates in the Wnt signalling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as a repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. Location: Nucleus, PML body; Nucleus (UniProt). Locus 10q25.2-q25.3 (HGNC).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 7-15% | Mutation or VTI1A-TCF7L2 fusion | cBioPortal: 1,088 of 7,237, 15.0%, in crc_msk_2026; 124 of 1,134, 10.9%, in crc_msk_2017; 58 of 534, 10.9%, in coadread_tcga_pan_can_atlas_2018; 44 of 619, 7.1%, in coadread_dfci_2016. Structural variants involving TCF7L2 appear in 4 of 594 TCGA samples (VTI1A-TCF7L2 in 3) and 12 of 7,237 in crc_msk_2026. Recurrent TCF7L2 mutations were among the new findings of the Genentech exome and transcriptome series, and the TCGA analysis reported a NAV2-TCF7L1 fusion (Seshagiri 2012, Cancer Genome Atlas Network 2012). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It gave the WNT pathway a second, druggable entry point: RSPO fusion tumours still need the upstream receptor complex, so they are the population porcupine and RSPO3 inhibitors are being tested in.
It is the reference description of the disease and the source of the hypermutated split that decides who gets immunotherapy; it also put HER2 on the colorectal map as a drug target.
Query for this target: (TITLE:"TCF7L2" OR ABSTRACT:"TCF7L2" OR TITLE:"transcription factor 7 like 2" OR ABSTRACT:"transcription factor 7 like 2" OR TITLE:"Transcription factor 7-like 2" OR ABSTRACT:"Transcription factor 7-like 2" OR TITLE:"TCF-4" OR ABSTRACT:"TCF-4" OR TITLE:"TCF4" OR ABSTRACT:"TCF4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TCF7L2, not a curated reading list.
Shares Recurrent R-spondin fusions in colon cancer, Wnt / β-catenin, IntOGen, Breast cancer (all types).
Shares Comprehensive molecular characterization of human colon and rectal cancer, Wnt / β-catenin, Skin cancer (all types), IntOGen.
Shares Recurrent R-spondin fusions in colon cancer, Wnt / β-catenin, Breast cancer (all types), Open Targets Platform.
Shares Comprehensive molecular characterization of human colon and rectal cancer, IntOGen, Open Targets Platform, Colorectal cancer.
Shares Comprehensive molecular characterization of human colon and rectal cancer, IntOGen, Breast cancer (all types), Open Targets Platform.
Shares Recurrent R-spondin fusions in colon cancer, Comprehensive molecular characterization of human colon and rectal cancer, Wnt / β-catenin, Hepatocellular carcinoma.
Shares Wnt / β-catenin, Open Targets Platform.
Shares Wnt / β-catenin, Rectal cancer, Colorectal cancer.