TCF7L2
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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).
External identifiers
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)
Biology
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).
- Colorectal cancer: Open Targets association 0.76 with colorectal cancer (MONDO_0005575); IntOGen driver in 5 cohorts (COAD, COADREAD)
- Breast cancer: Open Targets association 0.65 with breast cancer (MONDO_0007254)
- Prostate cancer: Open Targets association 0.60 with prostate cancer (MONDO_0008315)
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
- Rectal cancer: IntOGen driver in 1 cohort (READ)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 7 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery 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.
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