TNFSF15 (TNF Superfamily Member 15): Gene, Function, and Clinical Significance
A comprehensive overview of the TNFSF15 gene, including its genomic context, expression patterns, associated diseases, and mutational landscape.
Gene Information Card
| Symbol | TNFSF15 |
|---|---|
| Full Name | TNF Superfamily Member 15 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q32 |
| NCBI Gene ID | 9966 ncbi.nlm.nih.gov/gene/9966 |
| Ensembl ID | ENSG00000181634 |
| UniProt ID | O95150 |
| OMIM ID | 604052 |
| HGNC ID | 11931 |
| Aliases | TL1A; VEGI; TL1; MGC129934; MGC129935 |
Description
TNFSF15 encodes a member of the tumor necrosis factor (TNF) superfamily, specifically TNF superfamily member 15, also known as TL1A. This cytokine is primarily expressed on endothelial cells and plays a critical role in the regulation of immune responses, particularly in the gut. It binds to death receptor 3 (DR3) and decoy receptor 3 (DcR3), modulating T-cell activation and cytokine production. TNFSF15 has been implicated in inflammatory bowel disease (IBD), asthma, and certain cancers, making it a significant target for therapeutic intervention.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease (Crohn's disease, Ulcerative colitis) | TNFSF15 variants are associated with increased expression and signaling through DR3, promoting Th1/Th17 responses and intestinal inflammation. | Genome-wide association studies (GWAS) and functional studies (e.g., PMID: 21102463, 22158418) |
| Asthma | TNFSF15 may contribute to airway inflammation via DR3 signaling on T cells, enhancing Th2 cytokine production. | Association studies and experimental models (e.g., PMID: 20010862) |
| Rheumatoid Arthritis | Elevated TNFSF15 levels in synovial fluid may drive inflammatory cytokine production and joint damage. | Clinical and experimental evidence (e.g., PMID: 21931359) |
| Cancer (e.g., colorectal, breast) | TNFSF15 can have dual roles: anti-angiogenic effects via VEGI isoform, but also pro-inflammatory effects that may promote tumorigenesis in certain contexts. | Expression studies and functional assays (e.g., PMID: 15696205, 19029969) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 12.3 | Medium |
| Colon | 10.8 | Medium |
| Lung | 8.5 | Low |
| Spleen | 7.2 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 25.4 | High expression; key source of TNFSF15 |
| Jurkat (T-cell leukemia) | 2.3 | Low expression; inducible upon activation |
| HeLa (cervical carcinoma) | 1.8 | Low expression |
| A549 (lung carcinoma) | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6478108 | SNP (intronic) | ~30% (minor allele frequency) | Associated with increased risk of Crohn's disease; may affect splicing or regulatory elements. |
| rs6478109 | SNP (intronic) | ~25% | Linked to IBD susceptibility; functional impact unclear. |
| rs4263839 | SNP (intronic) | ~20% | Associated with ulcerative colitis risk. |
| c.416C>T (p.Pro139Leu) | Missense | Rare (<0.1%) | Potential loss-of-function; reduced receptor binding in vitro. |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Pro139Leu) may impair protein folding or receptor binding, leading to reduced signaling. Complete loss-of-function is rare and not well-documented in human populations.
Gain of Function (GOF)
Common risk alleles (e.g., rs6478108) are associated with increased TNFSF15 expression, leading to enhanced DR3 signaling and pro-inflammatory responses.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported for TNFSF15.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • tumor necrosis factor receptor binding |
| • signaling receptor binding | • extracellular space |
| • membrane | • immune response |
| • inflammatory response | • cell surface receptor signaling pathway |
| • positive regulation of T cell proliferation | • negative regulation of angiogenesis |
Pathways
• TNF signaling pathway (KEGG hsa04668)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• T cell receptor signaling pathway (KEGG hsa04660)
• Apoptosis (KEGG hsa04210)
Protein Summary
The TNFSF15 protein, also known as TL1A, is a type II transmembrane protein that can be cleaved to a soluble form. It is a homotrimeric cytokine that binds to death receptor 3 (DR3) on T cells, NK cells, and other immune cells, promoting cell survival, proliferation, and cytokine production. It also binds to decoy receptor 3 (DcR3), which neutralizes its activity. TNFSF15 is involved in Th1 and Th17 responses, and its dysregulation is linked to autoimmune and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFSF15 Knockout HEK293 Cell Line | EDJ-KQ50921 | Human | 9966 | Details Get a Quote |
| TNFSF15 Knockout HeLa Cell Line | EDJ-KQ55288 | Human | 9966 | Details Get a Quote |
| TNFSF15 Knockout A-549 Cell Line | EDJ-KQ63770 | Human | 9966 | Details Get a Quote |
| TNFSF15 Knockout HCT 116 Cell Line | EDJ-KQ72229 | Human | 9966 | Details Get a Quote |
