# BIRC3

Source: https://onco.cc/targets/birc3/  
OnCo record `birc3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

BIRC3 (Baculoviral IAP repeat-containing protein 3) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Leukaemia, Skin cancer and 4 more.

## Summary

Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signalling and immunity, mitogenic kinase signalling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signalling and regulates both canonical and non-canonical NF-kappa-B signalling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signalling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10.

CIViC holds 2 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.63 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.00, somatic mutation 0.80, clinical 0.14). IntOGen calls it a driver in 2 cohorts (1 activating, 0 loss-of-function), covering Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Lung Squamous Cell Carcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: baculoviral IAP repeat containing 3; Baculoviral IAP repeat-containing protein 3; cIAP2; hiap-1; RNF49; MALT2; c-IAP2; API2
- Tags: cancer-genes-wave
- Symbol: BIRC3
- Class: oncogene
- Biology: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signalling and immunity, mitogenic kinase signalling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signalling and regulates both canonical and non-canonical NF-kappa-B signalling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signalling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signalling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Location: Cytoplasm; Nucleus (UniProt). Locus 11q22.2 (HGNC).
- Where found: Non-Hodgkin lymphoma: Open Targets association 0.62 with non-Hodgkin lymphoma (MONDO_0018908); Leukaemia: Open Targets association 0.59 with leukaemia (MONDO_0005059); Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898); Mantle cell lymphoma: CIViC evidence names this disease; Chronic lymphocytic leukaemia: CIViC evidence names this disease; IntOGen driver in 1 cohort (CLLSLL); Non-small-cell lung cancer: IntOGen driver in 1 cohort (LUSC)

## 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: Open Targets known-drug datatype score 0.14; IntOGen calls it an activating (Act) driver in 1 cohort; CIViC holds 2 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, t(11;18) API2-MALT1 and the NF-kB lesions of marginal zone lymphoma: Gastric MALT lymphoma begins as a Helicobacter-driven proliferation that still needs the antigen; removing the bacterium removes the stimulus and the lymphoma regresses. The t(11;18) fuses API2 to MALT1 and produces a protein that activates NF-kB on its own, so the lymphoma no longer needs the antigen and no longer cares whether the bacterium is still there. The related translocations, t(1;14) involving BCL10 and t(14;18) involving MALT1, do the same job by a different route, and inactivation of TNFAIP3 removes the brake. Frequency: Among 111 patients with Helicobacter-positive gastric MALT lymphoma treated with antibiotics, the translocation separated the responders from the non-responders: 47 of the 48 patients who regressed completely were negative for the API2-MALT1 transcript (Liu 2002). What it changes about treatment: Yes, and this is one of the few places where a translocation result changes the first decision. A t(11;18)-positive gastric MALT lymphoma should not be treated with eradication alone, whatever the stage; a negative one usually can be.

## Sources

- HGNC HGNC:591: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:591
- UniProt Q13489: https://www.uniprot.org/uniprotkb/Q13489/entry
- NCBI Gene 330: https://www.ncbi.nlm.nih.gov/gene/330
- Ensembl ENSG00000023445: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000023445
- Liu et al., Gastroenterology 2002: t(11;18) marks gastric MALT lymphomas that will not respond to Helicobacter pylori eradication (111 patients): https://doi.org/10.1053/gast.2002.33047

## 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: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)](https://onco.cc/cancers/malt-lymphoma/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- pathways: [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Microbiome-tumour interactions](https://onco.cc/pathways/microbiome-tumour/)

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