TNFRSF12A Gene: Fibroblast Growth Factor-Inducible 14 (Fn14)
Receptor for TNFSF12/TWEAK, Involved in Angiogenesis, Inflammation, and Cancer
Gene Information Card
| Symbol | TNFRSF12A |
|---|---|
| Full Name | TNF Receptor Superfamily Member 12A |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 51330 ncbi.nlm.nih.gov/gene/51330 |
| Ensembl ID | ENSG00000006327 |
| UniProt ID | Q9NP84 |
| OMIM ID | 605914 |
| HGNC ID | 11916 |
| Aliases | Fn14, CD266, TWEAKR, TweakR |
Description
TNFRSF12A (TNF Receptor Superfamily Member 12A), also known as Fn14, is a cell surface receptor that binds the cytokine TNFSF12/TWEAK. It is a type I transmembrane protein with a cysteine-rich extracellular domain and a cytoplasmic tail containing a TRAF-binding motif. TNFRSF12A activates NF-κB, MAPK, and PI3K/Akt signaling pathways, regulating cell proliferation, survival, migration, and inflammation. It is expressed in many tissues and is upregulated in response to injury, inflammation, and in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of TNFRSF12A promotes tumor cell proliferation, invasion, and angiogenesis via TWEAK-induced NF-κB and Akt activation. | NCBI Gene, COSMIC |
| Rheumatoid Arthritis | TWEAK/TNFRSF12A signaling contributes to synovial inflammation and joint destruction. | OMIM 605914 |
| Atherosclerosis | TNFRSF12A activation in endothelial cells and macrophages promotes vascular inflammation and plaque progression. | UniProt Q9NP84 |
| Acute Kidney Injury | Upregulation of TNFRSF12A in renal tubular cells mediates TWEAK-induced apoptosis and inflammation. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Medium |
| Lung | 6.5 | Medium |
| Liver | 4.1 | Low |
| Kidney | 7.8 | Medium |
| Placenta | 12.3 | High |
| Spleen | 10.1 | High |
| Thymus | 9.5 | High |
| Small Intestine | 5.6 | Medium |
| Colon | 4.9 | Low |
| Bone Marrow | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.2 | High expression |
| A549 (lung carcinoma) | 11.8 | High expression |
| HepG2 (hepatocellular carcinoma) | 7.3 | Medium expression |
| MCF7 (breast carcinoma) | 9.1 | Medium expression |
| K562 (leukemia) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of start codon; functional impact unknown |
| c.200C>T (p.Pro67Leu) | Missense | <0.01% | Rare variant; no known disease association |
| c.340G>A (p.Gly114Arg) | Missense | <0.01% | Located in extracellular domain; effect on ligand binding unclear |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in human disease; experimental knockout in mice shows reduced inflammation and tumor growth.
Gain of Function (GOF)
Overexpression or amplification of TNFRSF12A is observed in many cancers, leading to constitutive or enhanced TWEAK signaling.
Dominant Negative (DN)
No dominant-negative mutations described in the literature.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity (GO:0004872) | • tumor necrosis factor-activated receptor activity (GO:0005031) |
| • signal transduction (GO:0007165) | • activation of NF-κB-inducing kinase activity (GO:0007250) |
| • positive regulation of cell population proliferation (GO:0008284) | • integral component of membrane (GO:0016021) |
| • positive regulation of I-kappaB kinase/NF-κB signaling (GO:0043123) | • negative regulation of apoptotic process (GO:0043066) |
Pathways
• TWEAK Signaling Pathway (Reactome: R-HSA-933541)
• NF-κB Signaling (KEGG: hsa04064)
• TNF Receptor Superfamily Signaling (WikiPathways: WP231)
Protein Summary
TNFRSF12A (Fn14) is a 129-amino acid type I transmembrane receptor with a single cysteine-rich domain in the extracellular region. It binds specifically to the cytokine TWEAK (TNFSF12). Upon ligand binding, it recruits TRAF2 and TRAF5 to its cytoplasmic tail, leading to activation of the canonical and non-canonical NF-κB pathways, as well as MAPK and PI3K/Akt cascades. Fn14 is expressed at low levels in normal tissues but is highly upregulated in response to injury, inflammation, and in many solid tumors. Its signaling promotes cell survival, proliferation, migration, and angiogenesis, making it a potential therapeutic target in cancer and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF12A Knockout HEK293 Cell Line | EDJ-KQ51308 | Human | 51330 | Details Get a Quote |
| TNFRSF12A Knockout HeLa Cell Line | EDJ-KQ56288 | Human | 51330 | Details Get a Quote |
| TNFRSF12A Knockout A-549 Cell Line | EDJ-KQ64776 | Human | 51330 | Details Get a Quote |
| TNFRSF12A Knockout HCT 116 Cell Line | EDJ-KQ73225 | Human | 51330 | Details Get a Quote |
