TNFRSF25 (TNF Receptor Superfamily Member 25)
A key regulator of apoptosis and immune signaling, implicated in autoimmune diseases and cancer.
Gene Information Card
| Symbol | TNFRSF25 |
|---|---|
| Full Name | TNF Receptor Superfamily Member 25 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.31 |
| NCBI Gene ID | 8718 ncbi.nlm.nih.gov/gene/8718 |
| Ensembl ID | ENSG00000115718 |
| UniProt ID | Q93038 |
| OMIM ID | 603366 |
| HGNC ID | 11910 |
| Aliases | DR3, TRAMP, LARD, WSL-1, APO-3, DDR3 |
Description
TNFRSF25 (Tumor Necrosis Factor Receptor Superfamily Member 25), also known as DR3, is a cell surface receptor that belongs to the TNF receptor superfamily. It is a death receptor that can induce apoptosis and activate NF-κB signaling upon binding to its ligand TNFSF15 (TL1A). TNFRSF25 plays a critical role in regulating immune responses, particularly in T cell activation and differentiation. The gene is located on chromosome 1p36.31 and encodes a 417-amino acid protein. Alternative splicing generates multiple isoforms, including soluble forms that may modulate signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease (IBD) | TNFRSF25 signaling via TL1A promotes Th1/Th17 responses, contributing to intestinal inflammation. | ClinVar, OMIM |
| Rheumatoid Arthritis | Enhanced TNFRSF25 expression on synovial T cells correlates with disease activity. | NCBI Gene, OMIM |
| Asthma | Polymorphisms in TNFRSF25 are associated with increased risk and severity. | ClinVar, OMIM |
| Multiple Sclerosis | TL1A/TNFRSF25 axis drives pathogenic T cell responses in CNS. | OMIM, NCBI Gene |
| Cancer (various) | TNFRSF25 can act as a tumor suppressor via apoptosis induction; loss of expression is seen in some cancers. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Thymus | 8.9 | Medium |
| Bone marrow | 6.3 | Low |
| Lung | 4.1 | Low |
| Small intestine | 3.8 | Low |
| Colon | 3.5 | Low |
| Peripheral blood leukocytes | 15.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 18.2 | High expression |
| Raji (Burkitt lymphoma) | 9.7 | Medium expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 1.5 | Very low expression |
| K562 (chronic myeloid leukemia) | 7.4 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.625C>T (p.Arg209Trp) | Missense | <0.01% | Reported in ClinVar as likely benign; functional impact unclear. |
| c.1003G>A (p.Val335Met) | Missense | <0.01% | Uncertain significance; may affect receptor-ligand interaction. |
| c.1234delC (p.Leu412Trpfs*13) | Frameshift | <0.01% | Predicted loss-of-function; associated with immune dysregulation. |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss-of-function; no protein produced. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations (e.g., c.1234delC, c.1A>G) are predicted to result in truncated or absent protein, impairing apoptosis and immune regulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations are currently reported in ClinVar or COSMIC for TNFRSF25.
Dominant Negative (DN)
Some missense variants (e.g., p.Val335Met) may act in a dominant-negative manner by interfering with wild-type receptor signaling, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TNF signaling pathway (KEGG: hsa04668)
• Apoptosis (KEGG: hsa04210)
• NF-kappa B signaling pathway (KEGG: hsa04064)
• TL1A/TNFRSF25 signaling in T cell differentiation (Reactome: R-HSA-5673001)
Protein Summary
TNFRSF25 is a type I transmembrane protein of 417 amino acids (UniProt Q93038). It contains an extracellular cysteine-rich domain (CRD) characteristic of TNF receptors, a transmembrane domain, and an intracellular death domain (DD) that recruits adaptor proteins such as TRADD and FADD to activate caspase cascades and NF-κB. The protein is expressed predominantly on lymphocytes and plays a dual role in promoting apoptosis and pro-inflammatory signaling. Alternative splicing generates at least four isoforms, including a soluble form that may act as a decoy receptor. Post-translational modifications include N-glycosylation at Asn residues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF25 Knockout HEK293 Cell Line | EDJ-KQ6339 | Human | 8718 | Details Get a Quote |
| TNFRSF25 Knockout HCT 116 Cell Line | EDJ-KQ28972 | Human | 8718 | Details Get a Quote |
| TNFRSF25 Knockout A-549 Cell Line | EDJ-KQ30278 | Human | 8718 | Details Get a Quote |
| TNFRSF25 Knockout HeLa Cell Line | EDJ-KQ30279 | Human | 8718 | Details Get a Quote |
