# TCF3

Source: https://onco.cc/targets/tcf3/  
OnCo record `tcf3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: transcription factor 3; Transcription factor E2-alpha; E2A; ITF1; MGC129647; MGC129648; bHLHb21; E47; p75
- Tags: cancer-genes-wave
- Symbol: TCF3
- Class: transcription
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:11633: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11633
- UniProt P15923: https://www.uniprot.org/uniprotkb/P15923/entry
- NCBI Gene 6929: https://www.ncbi.nlm.nih.gov/gene/6929
- Ensembl ENSG00000071564: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000071564
- Schmitz et al., Nature 2012: Burkitt lymphoma pathogenesis from structural and functional genomics: https://doi.org/10.1038/nature11378

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/)

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JSON: https://onco.cc/api/v1/entities/tcf3.json