{"entity":{"id":"tcf7l2","kind":"target","name":"TCF7L2","aka":["transcription factor 7 like 2","Transcription factor 7-like 2","TCF-4","TCF4"],"tldr":"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.","summary":"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.\n\nOpen 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11641","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11641"},{"label":"UniProt Q9NQB0","url":"https://www.uniprot.org/uniprotkb/Q9NQB0/entry"},{"label":"NCBI Gene 6934","url":"https://www.ncbi.nlm.nih.gov/gene/6934"},{"label":"Ensembl ENSG00000148737","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000148737"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["colorectal","breast-cancer","prostate","hcc","skin-cancer","rectal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-seshagiri-rspo-fusions-colon-nature-2012","paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"journals":[],"dependsOn":[],"notes":["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.","Colorectal cancer: mutated in 7 to 15% and involved in the recurrent VTI1A-TCF7L2 fusion (3 of 594 TCGA samples on cBioPortal); recurrent TCF7L2 mutations were among the new findings of the Genentech exome and transcriptome series (Seshagiri 2012)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TCF7L2","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:11641","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11641","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NQB0","url":"https://www.uniprot.org/uniprotkb/Q9NQB0/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000148737","url":"https://platform.opentargets.org/target/ENSG00000148737/associations","note":"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)"},{"label":"IntOGen TCF7L2","url":"https://www.intogen.org/search?gene=TCF7L2","note":"driver in 7 cohorts (Act 0, LoF 7); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificitySources":[],"hgnc":"HGNC:11641","ensembl":"ENSG00000148737","uniprot":"Q9NQB0","entrez":"6934","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9065401/","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).","whereFound":["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)","Colorectal cancer: mutation or vti1a-tcf7l2 fusion 7-15%"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"colorectal","pct":"7-15","measure":"Mutation or VTI1A-TCF7L2 fusion","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"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)."}]},"route":"/targets/tcf7l2/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"paper":[{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","route":"/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/"},{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","route":"/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/"}]}}