{"entity":{"id":"traf3","kind":"target","name":"TRAF3","aka":["TNF receptor associated factor 3","TNF receptor-associated factor 3","CAP-1","CD40bp","CRAF1","LAP1","RNF118"],"tldr":"TRAF3 (TNF receptor-associated factor 3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.","summary":"Cytoplasmic E3 ubiquitin ligase that regulates various signalling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types. In TLR and RLR signalling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome. Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines.\n\nIntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12033","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12033"},{"label":"UniProt Q13114","url":"https://www.uniprot.org/uniprotkb/Q13114/entry"},{"label":"NCBI Gene 7187","url":"https://www.ncbi.nlm.nih.gov/gene/7187"},{"label":"Ensembl ENSG00000131323","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131323"}],"tags":["cancer-genes-wave"],"related":["intogen"],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"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 1 cohort. Evidence tier \"cohort-driver\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TRAF3","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:12033","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12033","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q13114","url":"https://www.uniprot.org/uniprotkb/Q13114/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen TRAF3","url":"https://www.intogen.org/search?gene=TRAF3","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:12033","ensembl":"ENSG00000131323","uniprot":"Q13114","entrez":"7187","biology":"Cytoplasmic E3 ubiquitin ligase that regulates various signalling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types. In TLR and RLR signalling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome. Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilising the exocyst complex to rapidly expel intracellular bacteria back for clearance. Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Location: Cytoplasm; Endosome; Mitochondrion (UniProt). Locus 14q32.32 (HGNC).","whereFound":["Multiple myeloma: IntOGen driver in 1 cohort (PCM)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/traf3/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}]}}