TNFAIP3
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
- 3 · How drugs use it
No product in this corpus aims at TNFAIP3 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:11896 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P21580 (protein name, function text, keywords and locations (REST API)); CIViC gene TNFAIP3 (1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000118503 (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)); IntOGen TNFAIP3 (driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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
top- 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.
Latest papers
topQuery for this target: (TITLE:"TNFAIP3" OR ABSTRACT:"TNFAIP3" OR TITLE:"TNF alpha induced protein 3" OR ABSTRACT:"TNF alpha induced protein 3" OR TITLE:"Tumor necrosis factor alpha-induced protein 3" OR ABSTRACT:"Tumor necrosis factor alpha-induced protein 3" OR TITLE:"A20" OR ABSTRACT:"A20" OR TITLE:"OTUD7C" OR ABSTRACT:"OTUD7C") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TNFAIP3, not a curated reading list.
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