# TRAF3

Source: https://onco.cc/targets/traf3/  
OnCo record `traf3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: TNF receptor associated factor 3; TNF receptor-associated factor 3; CAP-1; CD40bp; CRAF1; LAP1; RNF118
- Tags: cancer-genes-wave
- Symbol: TRAF3
- Class: tumor-suppressor
- 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).
- Where found: Multiple myeloma: IntOGen driver in 1 cohort (PCM)

## 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.

## Sources

- HGNC HGNC:12033: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12033
- UniProt Q13114: https://www.uniprot.org/uniprotkb/Q13114/entry
- NCBI Gene 7187: https://www.ncbi.nlm.nih.gov/gene/7187
- Ensembl ENSG00000131323: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131323

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/)
- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)

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JSON: https://onco.cc/api/v1/entities/traf3.json