TRAF3 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TRAF3 gene, its protein product, associated diseases, and molecular mechanisms.
Gene Information Card
| Symbol | TRAF3 |
|---|---|
| Full Name | TNF receptor associated factor 3 |
| Gene Type | protein coding |
| Chromosomal Location | 14q32.33 |
| NCBI Gene ID | 7187 ncbi.nlm.nih.gov/gene/7187 |
| Ensembl ID | ENSG00000131323 |
| UniProt ID | Q13114 |
| OMIM ID | 601896 |
| HGNC ID | 12029 |
| Aliases | CAP-1, CD40bp, CRAF1, LAP1 |
Description
The TRAF3 gene encodes TNF receptor-associated factor 3, a key adaptor protein that regulates signaling pathways for various TNF receptor superfamily members and pattern recognition receptors. TRAF3 plays a critical role in innate and adaptive immunity, particularly in type I interferon production, NF-κB activation, and B-cell survival. It also functions as a tumor suppressor in multiple cancers, especially in multiple myeloma and B-cell lymphomas. Mutations and deletions of TRAF3 are frequently observed in human malignancies and can lead to immune dysregulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple Myeloma | Loss-of-function mutations or deletions of TRAF3 lead to constitutive NF-κB activation, promoting plasma cell survival and proliferation. | COSMIC; frequent somatic mutations in multiple myeloma (e.g., ~10-15% of cases). |
| B-cell Lymphoma | Inactivating mutations and deletions of TRAF3 contribute to lymphomagenesis by deregulating NF-κB and B-cell survival pathways. | COSMIC; recurrent alterations in various B-cell lymphomas. |
| Herpes Simplex Encephalitis (HSE) | Heterozygous mutations in TRAF3 impair TLR3-mediated type I interferon responses, increasing susceptibility to HSV-1 encephalitis. | ClinVar; reported in patients with HSE. |
| Common Variable Immunodeficiency (CVID) | TRAF3 mutations may disrupt B-cell signaling and antibody production, contributing to CVID phenotype. | ClinVar; rare variants reported. |
| Waldenström Macroglobulinemia | TRAF3 deletions or mutations are found in a subset of cases, leading to NF-κB activation and tumor growth. | COSMIC; somatic alterations observed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymphoid tissues (spleen, lymph node, tonsil) | High (e.g., >50 nTPM) | High expression in immune cells. |
| Bone marrow | Moderate (e.g., 20-50 nTPM) | Expression in hematopoietic cells. |
| Liver | Low (e.g., <10 nTPM) | Low expression. |
| Brain | Low (e.g., <10 nTPM) | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Ramos (Burkitt lymphoma) | High (e.g., >50 nTPM) | B-cell line with high TRAF3 expression. |
| K562 (chronic myeloid leukemia) | Moderate (e.g., 20-50 nTPM) | Myeloid cell line. |
| HeLa (cervical carcinoma) | Low (e.g., <10 nTPM) | Epithelial cell line. |
| HepG2 (hepatocellular carcinoma) | Low (e.g., <10 nTPM) | Liver cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1120C>T (p.Arg374Ter) | Nonsense | Rare (somatic) | Truncated protein, loss of function. |
| c.1129A>G (p.Lys377Glu) | Missense | Rare (somatic) | Impaired TRAF3 function. |
| Deletion of 14q32.33 | Copy number loss | Frequent in multiple myeloma | Loss of heterozygosity, reduced TRAF3 expression. |
| c.1180G>A (p.Glu394Lys) | Missense | Rare (germline) | Impaired TLR3 signaling, associated with HSE. |
Mutation functional classification
Loss of Function (LOF)
Most TRAF3 mutations in cancer are loss-of-function, leading to constitutive NF-κB activation and enhanced cell survival.
Gain of Function (GOF)
Gain-of-function mutations are rare; some variants may enhance TRAF3 activity but are not well characterized.
Dominant Negative (DN)
Certain missense mutations may act in a dominant-negative manner, interfering with wild-type TRAF3 function in signaling complexes.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • signal transducer activity |
| • ubiquitin protein ligase binding | • zinc ion binding |
| • cytoplasm | • cytosol |
| • nucleus | • TNF receptor-associated factor complex |
| • regulation of NF-kappaB signaling | • innate immune response |
| • type I interferon signaling pathway | • B cell homeostasis |
Pathways
• TNF receptor signaling pathway
• TLR signaling pathway
• RIG-I-like receptor signaling pathway
• NF-kappaB signaling pathway
• Type I interferon production
• B cell receptor signaling
Protein Summary
TRAF3 is a 568-amino acid protein containing a RING finger domain, multiple zinc finger motifs, and a TRAF domain. It functions as a scaffold for signaling complexes, mediating ubiquitination events that regulate NF-κB and IRF3/7 activation. TRAF3 is essential for type I interferon production in response to viral infection and for B-cell survival and maturation. In cancer, loss of TRAF3 leads to aberrant NF-κB signaling, promoting tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRAF3 Knockout HEK293 Cell Line | EDJ-KQ602 | Human | 7187 | Details Get a Quote |
| TRAF3IP2 Knockout HEK293 Cell Line | EDJ-KQ7153 | Human | 10758 | Details Get a Quote |
| TRAF3IP3 Knockout HEK293 Cell Line | EDJ-KQ8779 | Human | 80342 | Details Get a Quote |
| TRAF3 Knockout A-549 Cell Line | EDJ-KQ19046 | Human | 7187 | Details Get a Quote |
| TRAF3 Knockout HCT 116 Cell Line | EDJ-KQ19047 | Human | 7187 | Details Get a Quote |
| TRAF3 Knockout HeLa Cell Line | EDJ-KQ19048 | Human | 7187 | Details Get a Quote |
| TRAF3IP2 Knockout A-549 Cell Line | EDJ-KQ32053 | Human | 10758 | Details Get a Quote |
| TRAF3IP2 Knockout HCT 116 Cell Line | EDJ-KQ32054 | Human | 10758 | Details Get a Quote |
| TRAF3IP2 Knockout HeLa Cell Line | EDJ-KQ30676 | Human | 10758 | Details Get a Quote |
| TRAF3IP3 Knockout HeLa Cell Line | EDJ-KQ57331 | Human | 80342 | Details Get a Quote |
| TRAF3IP3 Knockout A-549 Cell Line | EDJ-KQ65837 | Human | 80342 | Details Get a Quote |
| TRAF3IP3 Knockout HCT 116 Cell Line | EDJ-KQ74262 | Human | 80342 | Details Get a Quote |
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