TRAF6 Gene: A Key Mediator of Innate and Adaptive Immune Signaling
TNF Receptor Associated Factor 6: Function, Expression, and Clinical Relevance
Gene Information Card
| Symbol | TRAF6 |
|---|---|
| Full Name | TNF receptor associated factor 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p12 |
| NCBI Gene ID | 7189 ncbi.nlm.nih.gov/gene/7189 |
| Ensembl ID | ENSG00000175104 |
| UniProt ID | Q9Y4K3 |
| OMIM ID | 602355 |
| HGNC ID | 12036 |
| Aliases | RNF85, MGC:3310, TRAF6_HUMAN |
Description
TRAF6 (TNF receptor associated factor 6) is a member of the TRAF family of proteins that functions as a signal transducer for members of the TNF receptor superfamily and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily. It mediates activation of NF-kB and MAP kinases, playing a critical role in innate and adaptive immunity, inflammation, and bone metabolism. TRAF6 possesses E3 ubiquitin ligase activity and is involved in the ubiquitination of target proteins to propagate signaling cascades.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency (e.g., hyper-IgM syndrome) | Loss-of-function mutations impair CD40 signaling, leading to defective B cell class switching and antibody production | OMIM #602355; PMID: 19360006 |
| Gastric cancer | Overexpression and amplification of TRAF6 promote NF-kB activation and tumor progression | COSMIC; PMID: 25670082 |
| Breast cancer | TRAF6 overexpression correlates with poor prognosis and enhanced NF-kB signaling | COSMIC; PMID: 23431171 |
| Osteoporosis | TRAF6 mediates RANK signaling essential for osteoclast differentiation; dysregulation leads to bone loss | OMIM #602355; PMID: 10559971 |
| Inflammatory bowel disease | TRAF6 variants associated with altered TLR signaling and chronic inflammation | ClinVar; PMID: 21706002 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Bone marrow | 10.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Brain | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression in embryonic kidney cells |
| HeLa | 14.2 | Cervical cancer cell line |
| K562 | 11.9 | Leukemia cell line |
| MCF7 | 9.6 | Breast cancer cell line |
| HepG2 | 7.3 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118G>A (p.Glu40Lys) | Missense | Rare | Loss of function; impaired CD40 signaling |
| c.487C>T (p.Arg163Trp) | Missense | Rare | Loss of function; associated with hyper-IgM syndrome |
| c.1045A>G (p.Asn349Asp) | Missense | Rare | Gain of function; enhanced NF-kB activation |
| Amplification | Copy number gain | Frequent in gastric cancer | Overexpression; promotes tumorigenesis |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Glu40Lys, p.Arg163Trp) impair TRAF6 ubiquitin ligase activity or protein stability, leading to defective immune signaling and primary immunodeficiency.
Gain of Function (GOF)
Missense mutations (e.g., p.Asn349Asp) enhance TRAF6-mediated NF-kB activation, contributing to inflammatory and oncogenic phenotypes.
Dominant Negative (DN)
Dominant-negative TRAF6 mutants (e.g., truncated forms lacking the RING finger domain) inhibit wild-type TRAF6 function, blocking downstream signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-kB signaling pathway (KEGG: hsa04064)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• RANK signaling in osteoclastogenesis (KEGG: hsa04380)
• CD40 signaling pathway (Reactome: R-HSA-5621575)
• IL-1 signaling pathway (Reactome: R-HSA-446652)
Protein Summary
TRAF6 is a 522-amino acid protein containing an N-terminal RING finger domain (E3 ubiquitin ligase), a zinc finger domain, and a C-terminal TRAF domain. It functions as a scaffold and ubiquitin ligase, catalyzing K63-linked polyubiquitination of target proteins such as IKKγ (NEMO) and IRAK1, leading to activation of NF-kB and MAPK pathways. TRAF6 is essential for signaling from TNFR superfamily members (e.g., CD40, RANK) and IL-1R/TLR family members. Its dysregulation is implicated in immune deficiencies, inflammatory diseases, and cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRAF6 Knockout HEK293 Cell Line | EDJ-KQ107 | Human | 7189 | Details Get a Quote |
| TRAF6 Knockout A-549 Cell Line | EDJ-KQ19052 | Human | 7189 | Details Get a Quote |
| TRAF6 Knockout HCT 116 Cell Line | EDJ-KQ19053 | Human | 7189 | Details Get a Quote |
| TRAF6 Knockout HeLa Cell Line | EDJ-KQ19054 | Human | 7189 | Details Get a Quote |
| Traf6 Knockout HBZY-1 Cell Line | EDJ-KZ6 | Rat | 7189 | Details Get a Quote |
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