# ID3

Source: https://onco.cc/targets/id3/  
OnCo record `id3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

ID3 (DNA-binding protein inhibitor ID-3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Burkitt lymphoma and Diffuse large B-cell lymphoma.

## Summary

Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. IntOGen calls it a driver in 5 cohorts (0 activating, 5 loss-of-function), covering Burkitt Lymphoma, Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma, Non-Hodgkin Lymphoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: inhibitor of DNA binding 3; DNA-binding protein inhibitor ID-3; HEIR-1; bHLHb25
- Tags: cancer-genes-wave
- Symbol: ID3
- Class: tumor-suppressor
- Biology: Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Location: Nucleus (UniProt). Locus 1p36.12 (HGNC).
- Where found: Non-Hodgkin lymphoma: Open Targets association 0.61 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL); Burkitt lymphoma: Open Targets association 0.51 with Burkitt lymphoma (MONDO_0007243); CIViC evidence names this disease; Diffuse large B-cell lymphoma: IntOGen driver in 1 cohort (DLBCLNOS)

## 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 5 cohorts; CIViC holds 1 clinical evidence items on its variants. 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:5362: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5362
- UniProt Q02535: https://www.uniprot.org/uniprotkb/Q02535/entry
- NCBI Gene 3399: https://www.ncbi.nlm.nih.gov/gene/3399
- Ensembl ENSG00000117318: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000117318
- 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/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- 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/id3.json