TRAF4 Gene - TNF Receptor Associated Factor 4
A key adaptor protein in immune signaling and cancer biology
Gene Information Card
| Symbol | TRAF4 |
|---|---|
| Full Name | TNF receptor associated factor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 7178 ncbi.nlm.nih.gov/gene/7178 |
| Ensembl ID | ENSG00000176697 |
| UniProt ID | Q9BUZ4 |
| OMIM ID | 602464 |
| HGNC ID | 12034 |
| Aliases | CART1, MLN62, RNF83 |
Description
TRAF4 (TNF receptor associated factor 4) is a member of the TRAF family of adaptor proteins that mediate signal transduction from TNF receptors and other immune receptors. It contains a RING-type zinc finger domain and is involved in NF-kappaB activation, JNK signaling, and regulation of cell survival, proliferation, and differentiation. TRAF4 is overexpressed in various cancers and plays roles in both innate and adaptive immunity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression and amplification of TRAF4 promote tumor growth and metastasis via NF-kappaB and AKT pathways | PMID: 23563182; COSMIC |
| Lung cancer | TRAF4 upregulation correlates with poor prognosis and enhances cell migration | PMID: 25605247; COSMIC |
| Prostate cancer | TRAF4 expression is elevated and associated with androgen receptor signaling | PMID: 26921324; COSMIC |
| Inflammatory diseases | TRAF4 modulates TLR and IL-1 receptor signaling, contributing to inflammation | PMID: 16920924 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.7 | Medium |
| Breast | 6.3 | Low |
| Prostate | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | High expression; consistent with overexpression in breast cancer |
| A549 (lung cancer) | 12.8 | Elevated expression |
| HEK293 (embryonic kidney) | 8.2 | Moderate expression |
| K562 (leukemia) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.437C>T (p.Thr146Met) | Missense | <0.1% | Unknown functional impact; reported in COSMIC |
| c.112G>A (p.Gly38Arg) | Missense | <0.1% | Located in RING domain; may affect ubiquitin ligase activity |
| Amplification | Copy number gain | ~5% in breast cancer | Associated with increased TRAF4 expression and poor prognosis |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in human disease; experimental knockdown reduces NF-kappaB signaling.
Gain of Function (GOF)
Amplification and overexpression in cancers suggest gain-of-function role in tumorigenesis.
Dominant Negative (DN)
Not described for TRAF4; some TRAF family members have dominant-negative forms, but not confirmed for TRAF4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-kappaB signaling pathway (Reactome: R-HSA-168256)
• TNF receptor superfamily signaling (Reactome: R-HSA-73887)
• Toll-like receptor signaling (Reactome: R-HSA-168898)
• IL-1 signaling (Reactome: R-HSA-446652)
Protein Summary
TRAF4 is a 470-amino acid protein with a RING finger domain, two TRAF-type zinc fingers, and a C-terminal TRAF domain. It functions as an E3 ubiquitin ligase and adaptor protein, linking TNF receptor superfamily members to downstream signaling cascades. TRAF4 is unique among TRAFs in being predominantly nuclear in some cell types and is implicated in cell polarity, migration, and cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRAF4 Knockout HEK293 Cell Line | EDJ-KQ6659 | Human | 9618 | Details Get a Quote |
| TRAF4 Knockout A-549 Cell Line | EDJ-KQ30957 | Human | 9618 | Details Get a Quote |
| TRAF4 Knockout HCT 116 Cell Line | EDJ-KQ30958 | Human | 9618 | Details Get a Quote |
| TRAF4 Knockout HeLa Cell Line | EDJ-KQ29605 | Human | 9618 | Details Get a Quote |
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