TNFSF12 (TNF Superfamily Member 12)
Key regulator of apoptosis, immune modulation, and angiogenesis; implicated in cancer and autoimmune diseases.
Gene Information Card
| Symbol | TNFSF12 |
|---|---|
| Full Name | TNF Superfamily Member 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 8742 ncbi.nlm.nih.gov/gene/8742 |
| Ensembl ID | ENSG00000139624 |
| UniProt ID | O43508 |
| OMIM ID | 602695 |
| HGNC ID | 11926 |
| Aliases | TWEAK, APO3L, DR3LG, TNLG4A |
Description
TNFSF12 (TNF Superfamily Member 12), also known as TWEAK, encodes a cytokine of the tumor necrosis factor (TNF) ligand family. It is a type II transmembrane protein that can be cleaved to a soluble form. TNFSF12 binds to its receptor FN14 (TNFRSF12A) and regulates multiple cellular processes including proliferation, migration, differentiation, apoptosis, and angiogenesis. It plays a key role in immune responses, tissue repair, and inflammation. Dysregulation of TNFSF12 is associated with various cancers, autoimmune diseases, and cardiovascular disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus | Overexpression of TNFSF12 promotes B-cell activation and autoantibody production via FN14 signaling. | ClinVar, NCBI Gene |
| Rheumatoid arthritis | TNFSF12 induces synovial fibroblast proliferation and inflammatory cytokine release. | NCBI Gene, OMIM |
| Colorectal cancer | TNFSF12/FN14 signaling enhances tumor cell survival and angiogenesis. | COSMIC, NCBI Gene |
| Breast cancer | Elevated TNFSF12 expression correlates with poor prognosis and metastasis. | COSMIC, NCBI Gene |
| Atherosclerosis | TNFSF12 promotes endothelial cell activation and vascular inflammation. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 8.3 | Medium |
| Heart | 6.2 | Low |
| Liver | 4.1 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 9.7 | Moderate expression in cervical cancer cells |
| K562 | 7.4 | Moderate expression in leukemia cells |
| HepG2 | 5.1 | Low expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200G>A (p.Arg67Gln) | Missense | 0.01% | Unknown functional impact; rare in population databases |
| c.341C>T (p.Pro114Leu) | Missense | 0.005% | Potential loss of receptor binding affinity |
| c.487A>G (p.Asn163Asp) | Missense | 0.002% | Reported in COSMIC; possible gain-of-function in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt receptor binding or protein stability, such as p.Pro114Leu, may reduce TNFSF12 activity.
Gain of Function (GOF)
Mutations like p.Asn163Asp may enhance FN14 signaling, promoting cell survival in tumors.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for TNFSF12.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TWEAK Signaling Pathway (Reactome: R-HSA-8849470)
• TNF Signaling Pathway (KEGG: hsa04668)
• Apoptosis (KEGG: hsa04210)
• NF-kappa B Signaling (KEGG: hsa04064)
Protein Summary
The TNFSF12 protein (TWEAK) is a 249-amino-acid type II transmembrane protein with a C-terminal TNF homology domain. It exists as a homotrimer and can be cleaved by furin to generate a soluble form. TWEAK binds specifically to the FN14 receptor, activating downstream pathways including NF-κB, MAPK, and PI3K/AKT. It is involved in tissue repair, inflammation, and immune regulation. Overexpression in tumors contributes to cancer progression and resistance to therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFSF12 Knockout HEK293 Cell Line | EDJ-KQ50821 | Human | 8742 | Details Get a Quote |
| TNFSF12-TNFSF13 Knockout HEK293 Cell Line | EDJ-KQ52333 | Human | 407977 | Details Get a Quote |
| TNFSF12 Knockout HeLa Cell Line | EDJ-KQ54995 | Human | 8742 | Details Get a Quote |
| TNFSF12-TNFSF13 Knockout HeLa Cell Line | EDJ-KQ60352 | Human | 407977 | Details Get a Quote |
| TNFSF12 Knockout A-549 Cell Line | EDJ-KQ63478 | Human | 8742 | Details Get a Quote |
| TNFSF12-TNFSF13 Knockout A-549 Cell Line | EDJ-KQ68819 | Human | 407977 | Details Get a Quote |
| TNFSF12 Knockout HCT 116 Cell Line | EDJ-KQ71946 | Human | 8742 | Details Get a Quote |
| TNFSF12-TNFSF13 Knockout HCT 116 Cell Line | EDJ-KQ77183 | Human | 407977 | Details Get a Quote |
