# TNFAIP3

Source: https://onco.cc/targets/tnfaip3/  
OnCo record `tnfaip3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

TNFAIP3 (Tumour necrosis factor alpha-induced protein 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, Leukaemia, Skin cancer and 2 more.

## Summary

Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signalled by cytokines, such as TNF and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signalling pathways.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.62 (direct and indirect evidence; datatypes literature 0.98, animal model 0.53, genetic association 0.06, somatic mutation 0.95). IntOGen calls it a driver in 3 cohorts (0 activating, 3 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: TNF alpha induced protein 3; Tumor necrosis factor alpha-induced protein 3; A20; OTUD7C
- Tags: cancer-genes-wave
- Symbol: TNFAIP3
- Class: tumor-suppressor
- Biology: Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signalled by cytokines, such as TNF and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signalling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyses the formation of 'Lys-48'-polyubiquitin chains. Location: Cytoplasm; Nucleus; Lysosome (UniProt). Locus 6q23.3 (HGNC).
- Where found: Non-Hodgkin lymphoma: Open Targets association 0.69 with non-Hodgkin lymphoma (MONDO_0018908); Leukaemia: Open Targets association 0.54 with leukaemia (MONDO_0005059); Skin cancer: Open Targets association 0.53 with skin cancer (MONDO_0002898); Diffuse large B-cell lymphoma: Open Targets association 0.65 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease; Marginal zone lymphoma: Open Targets association 0.52 with marginal zone lymphoma (MONDO_0017604)

## 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 3 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.

## Sources

- HGNC HGNC:11896: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11896
- UniProt P21580: https://www.uniprot.org/uniprotkb/P21580/entry
- NCBI Gene 7128: https://www.ncbi.nlm.nih.gov/gene/7128
- Ensembl ENSG00000118503: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118503

## 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: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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