{"entity":{"id":"tnfaip3","kind":"target","name":"TNFAIP3","aka":["TNF alpha induced protein 3","Tumor necrosis factor alpha-induced protein 3","A20","OTUD7C"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11896","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11896"},{"label":"UniProt P21580","url":"https://www.uniprot.org/uniprotkb/P21580/entry"},{"label":"NCBI Gene 7128","url":"https://www.ncbi.nlm.nih.gov/gene/7128"},{"label":"Ensembl ENSG00000118503","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118503"},{"label":"Liu et al., Gastroenterology 2002: t(11;18) marks gastric MALT lymphomas that will not respond to Helicobacter pylori eradication (111 patients)","url":"https://doi.org/10.1053/gast.2002.33047"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","leukaemia","skin-cancer","dlbcl","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["inflammation-nfkb","microbiome-tumour"],"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: 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.","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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TNFAIP3","role":["tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11896","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11896","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P21580","url":"https://www.uniprot.org/uniprotkb/P21580/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TNFAIP3","url":"https://civicdb.org/features/5828","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000118503","url":"https://platform.opentargets.org/target/ENSG00000118503/associations","note":"association with cancer (MONDO_0004992) 0.62; per-cancer scores at or above 0.5: diffuse large B-cell lymphoma 0.65, non-Hodgkin lymphoma 0.69, skin cancer 0.53, leukaemia 0.54, marginal zone lymphoma 0.52 (GraphQL API, CC0)"},{"label":"IntOGen TNFAIP3","url":"https://www.intogen.org/search?gene=TNFAIP3","note":"driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it a tumour suppressor (IntOGen finds it knocked out more often than chance); 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 TNFAIP3: RNA tissue enhanced (bone marrow 394 nTPM, urinary bladder 146 nTPM); high antibody staining in 2 normal tissues. Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Leukaemia, Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (diffuse large B-cell lymphoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P21580","url":"https://www.uniprot.org/uniprotkb/P21580/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TNFAIP3","url":"https://civicdb.org/features/5828","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen TNFAIP3","url":"https://www.intogen.org/search?gene=TNFAIP3","note":"driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas TNFAIP3 tissue","url":"https://www.proteinatlas.org/ENSG00000118503-TNFAIP3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000118503 associations","url":"https://platform.opentargets.org/target/ENSG00000118503/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11896","ensembl":"ENSG00000118503","uniprot":"P21580","entrez":"7128","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Opipari A.W. Jr. et al, J. Biol. Chem, 1990, \"The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2118515/","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).","whereFound":["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)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/tnfaip3/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"}]}}