TNFSF4 (OX40L) Gene
Tumor Necrosis Factor Superfamily Member 4
Gene Information Card
| Symbol | TNFSF4 |
|---|---|
| Full Name | Tumor Necrosis Factor Superfamily Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.1 |
| NCBI Gene ID | 7292 ncbi.nlm.nih.gov/gene/7292 |
| Ensembl ID | ENSG00000117586 |
| UniProt ID | P23510 |
| OMIM ID | 603594 |
| HGNC ID | 11934 |
| Aliases | OX40L, CD252, TXGP1, gp34 |
Description
TNFSF4 (Tumor Necrosis Factor Superfamily Member 4) encodes the OX40 ligand (OX40L), a type II transmembrane glycoprotein belonging to the TNF superfamily. OX40L is primarily expressed on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells, and binds to its receptor OX40 (CD134) on activated T cells. This interaction provides a critical costimulatory signal for T cell proliferation, survival, and effector function, playing a key role in immune responses, inflammation, and autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | TNFSF4 polymorphisms increase OX40L expression, enhancing T cell costimulation and autoantibody production | GWAS and case-control studies (OMIM 603594) |
| Atherosclerosis | OX40L promotes T cell activation and endothelial inflammation, contributing to plaque formation | Animal models and human genetic association studies (NCBI Gene) |
| Asthma | OX40L on dendritic cells drives Th2 cell differentiation and airway inflammation | Expression and functional studies (UniProt P23510) |
| Graft-versus-host disease (GVHD) | OX40-OX40L interaction amplifies alloreactive T cell responses | Preclinical models (ClinVar) |
| Cancer (various) | OX40L expression on tumor cells or APCs can modulate antitumor immunity; both agonistic and antagonistic strategies are explored | Therapeutic targeting in clinical trials (COSMIC) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.3 | Medium |
| Tonsil | 8.7 | Medium |
| Appendix | 6.2 | Low |
| Bone marrow | 4.1 | Low |
| Lung | 3.5 | Low |
| Small intestine | 2.8 | Low |
| Colon | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Dendritic cells (monocyte-derived) | 15.2 | High expression |
| Macrophages (M1) | 11.8 | High expression |
| B cells (activated) | 9.5 | Medium expression |
| T cells (resting) | 0.5 | Very low expression |
| HEK293 | 0.2 | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1234314 (intronic) | SNP | ~0.30 (Asian) | Associated with increased OX40L expression and SLE risk |
| rs2205960 (intronic) | SNP | ~0.25 (European) | Risk allele for SLE and atherosclerosis |
| rs3850641 (intronic) | SNP | ~0.20 (African) | Linked to asthma susceptibility |
| Missense variants (rare) | Missense | <0.01 | Functional impact unknown; not recurrent in COSMIC |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in human disease; knockout mice show impaired T cell responses.
Gain of Function (GOF)
Polymorphisms (e.g., rs1234314) associated with increased OX40L expression are considered gain-of-function in immune activation.
Dominant Negative (DN)
Not described for TNFSF4.
View complete mutation data：
Gene Ontology (GO)
| • TNF receptor binding (GO:0005164) | • cytokine activity (GO:0005125) |
| • tumor necrosis factor receptor superfamily binding (GO:0032813) | • immune response (GO:0006955) |
| • positive regulation of T cell proliferation (GO:0042102) | • positive regulation of NF-kappaB transcription factor activity (GO:0051092) |
| • cell surface (GO:0009986) | • integral component of membrane (GO:0016021) |
Pathways
• TNF signaling pathway (KEGG hsa04668)
• T cell receptor signaling pathway (KEGG hsa04660)
• NF-kappa B signaling pathway (KEGG hsa04064)
• OX40 signaling pathway (Reactome R-HSA-5668541)
• Costimulation by the CD28 family (Reactome R-HSA-389356)
Protein Summary
The TNFSF4 protein (OX40L, CD252) is a 183-amino acid type II transmembrane protein with a short cytoplasmic tail and a C-terminal extracellular TNF homology domain. It forms homotrimers and binds to the OX40 receptor (CD134) on activated T cells. OX40L is induced on APCs by inflammatory stimuli (e.g., CD40L, LPS) and provides a potent costimulatory signal that enhances T cell survival, cytokine production, and memory formation. The OX40L-OX40 axis is a key regulator of adaptive immunity and a therapeutic target for autoimmune diseases and cancer immunotherapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFSF4 Knockout HEK293 Cell Line | EDJ-KQ2451 | Human | 7292 | Details Get a Quote |
| TNFSF4 Knockout HCT 116 Cell Line | EDJ-KQ22980 | Human | 7292 | Details Get a Quote |
| TNFSF4 Knockout HeLa Cell Line | EDJ-KQ54709 | Human | 7292 | Details Get a Quote |
| TNFSF4 Knockout A-549 Cell Line | EDJ-KQ63199 | Human | 7292 | Details Get a Quote |
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