{"entity":{"id":"tcf3","kind":"target","name":"TCF3","aka":["transcription factor 3","Transcription factor E2-alpha","E2A","ITF1","MGC129647","MGC129648","bHLHb21","E47","p75"],"tldr":"TCF3 (Transcription factor E2-alpha) is a protein that switches other genes on and off. The public catalogues list it as a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Leukaemia, Non-Hodgkin lymphoma, Lung cancer and 3 more.","summary":"Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Together with TCF15, required for the mesenchymal to epithelial transition.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.00, somatic mutation 0.83).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11633","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11633"},{"label":"UniProt P15923","url":"https://www.uniprot.org/uniprotkb/P15923/entry"},{"label":"NCBI Gene 6929","url":"https://www.ncbi.nlm.nih.gov/gene/6929"},{"label":"Ensembl ENSG00000071564","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000071564"},{"label":"Schmitz et al., Nature 2012: Burkitt lymphoma pathogenesis from structural and functional genomics","url":"https://doi.org/10.1038/nature11378"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["leukaemia","non-hodgkin-lymphoma","lung-cancer","burkitt-lymphoma","all-leukemia","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","pi3k-akt-mtor","cell-cycle-engine-cdks"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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: CIViC holds 1 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Lymphoma, TCF3, ID3 and CCND3 in Burkitt lymphoma: A MYC translocation alone does not make a Burkitt lymphoma; it needs a partner that supplies survival. In Burkitt the partner is tonic B-cell receptor signalling through TCF3, the transcription factor also known as E2A: mutations either activate TCF3 or inactivate its negative regulator ID3, and TCF3 then switches on the PI3K pathway partly by augmenting tonic receptor signalling. A second, independent lesion drives the cell cycle directly, through CCND3 mutations that produce unusually stable cyclin D3. Frequency: TCF3 or ID3 mutation in 70% of sporadic Burkitt lymphoma cases and oncogenic CCND3 mutations in 38%, in a study combining high-throughput RNA sequencing with RNA interference screening (Schmitz 2012). What it changes about treatment: Not yet, and the gap is uncomfortable, because the regimens that cure Burkitt lymphoma are the most toxic in lymphoma and are the reason the disease is hard to treat in older patients and in low-resource settings, which is exactly where the endemic form occurs."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TCF3","role":["biomarker","fusion-partner"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11633","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11633","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P15923","url":"https://www.uniprot.org/uniprotkb/P15923/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TCF3","url":"https://civicdb.org/features/5646","note":"1 evidence items, 0 assertions, 1 variants; diseases: Burkitt Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000071564","url":"https://platform.opentargets.org/target/ENSG00000071564/associations","note":"association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.51, acute lymphoblastic leukaemia 0.58, non-Hodgkin lymphoma 0.61, lung cancer 0.53, leukaemia 0.61 (GraphQL API, CC0)"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it a fusion partner (UniProt records a translocation); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA TCF3: RNA low tissue specificity; high antibody staining in 5 normal tissues; highest cancer staining colorectal cancer (3 of 10 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Lymphoma, Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P15923","url":"https://www.uniprot.org/uniprotkb/P15923/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TCF3","url":"https://civicdb.org/features/5646","note":"1 evidence items, 0 assertions, 1 variants; diseases: Burkitt Lymphoma (GraphQL API, CC0)"},{"label":"Human Protein Atlas TCF3 tissue","url":"https://www.proteinatlas.org/ENSG00000071564-TCF3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000071564 associations","url":"https://platform.opentargets.org/target/ENSG00000071564/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11633","ensembl":"ENSG00000071564","uniprot":"P15923","entrez":"6929","firstDescribed":1989,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Murre et al, Cell, 1989, \"A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2493990/","biology":"Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Together with TCF15, required for the mesenchymal to epithelial transition. Dimers bind DNA on E-box motifs: 5'-CANNTG-3'. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region. Location: Nucleus (UniProt). Locus 19p13.3 (HGNC).","whereFound":["Leukaemia: Open Targets association 0.61 with leukaemia (MONDO_0005059)","Non-Hodgkin lymphoma: Open Targets association 0.61 with non-Hodgkin lymphoma (MONDO_0018908)","Lung cancer: Open Targets association 0.53 with lung cancer (MONDO_0008903)","Burkitt lymphoma: CIViC evidence names this disease","Acute lymphoblastic leukaemia: Open Targets association 0.58 with acute lymphoblastic leukaemia (MONDO_0004967)","Non-small-cell lung cancer: Open Targets association 0.51 with non-small cell lung carcinoma (MONDO_0005233)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/tcf3/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"cell-cycle-engine-cdks","kind":"pathway","name":"The cell-cycle engine (cyclins & CDKs)","route":"/pathways/cell-cycle-engine-cdks/"}]}}