The TNFRSF1B gene (TNF Receptor Superfamily Member 1B, also known as TNFR2 or p75) encodes a type I membrane receptor for tumor necrosis factor (TNF). Unlike TNFR1, TNFR2 primarily mediates neuroprotective and anti-inflammatory signaling in the central nervous system.
The TNFRSF1B gene is located on chromosome 1p36.22 and encodes TNF receptor 2 (TNFR2), a 75 kDa type I transmembrane glycoprotein[1]. While TNFRSF1A (TNFR1/p55) is ubiquitously expressed and primarily signals cell death and inflammation, TNFR2 has a restricted expression pattern and promotes cell survival, tissue repair, and immunomodulation[2]. In the nervous system, TNFR2 is expressed on neurons, oligodendrocytes, microglia, and astrocytes, where it mediates neuroprotective TNF signaling[3]. [1]
| | | [2]
|---|---| [3]
| Gene Symbol | TNFRSF1B | [4]
| Full Name | TNF Receptor Superfamily Member 1B | [5]
| Aliases | TNFR2, p75, CD120b, TNFBR |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 7133 |
| OMIM | 191191 |
| Ensembl | ENSG00000028137 |
| UniProt | P20333 |
| Associated Diseases | Neurodegeneration, autoimmune diseases, cancer |
TNFR2 is preferentially activated by transmembrane TNF (tmTNF) rather than soluble TNF, distinguishing it from TNFR1[1]:
In the CNS, TNFR2 mediates several protective mechanisms[3]:
TNFR2 plays critical roles in immune homeostasis[2]:
TNFR2 is significantly involved in AD pathobiology[4]:
TNFR2 modulates neuroinflammation in PD[5]:
TNFR2 is essential for CNS remyelination[6]:
| Variant | rsID | Effect | Clinical Significance |
|---|---|---|---|
| M196R | rs1061622 | Missense (exon 6) | Associated with modified AD risk, altered TNF signaling |
| T676G | rs1061624 | 3'UTR | Influences TNFRSF1B mRNA stability; associations with autoimmune disease |
| A1466G | rs3397 | 3'UTR | Modified receptor expression levels |
| -3609C/T | rs652625 | Promoter | Alters transcriptional activity |
| Feature | TNFR1 (TNFRSF1A | TNFR2 (TNFRSF1B) |
|---|---|---|
| Size | 55 kDa | 75 kDa |
| Expression | Ubiquitous | Restricted (immune cells, neurons, endothelium) |
| Ligand preference | Soluble TNF | Transmembrane TNF |
| Death domain | Yes (TRADD/FADD/caspase-8) | No |
| Primary signaling | Apoptosis, inflammation | Survival, tissue repair |
| CNS role | Neuroinflammation, neuronal death | Neuroprotection, remyelination |
TNFRSF1B has a more restricted expression pattern than TNFRSF1A[1]:
A key therapeutic strategy is to selectively activate TNFR2 without engaging TNFR1[7]:
Faustman D & Davis M, TNF receptor 2 pathway: drug target for autoimmune diseases (2010). 2010. ↩︎
Cheng X et al. TNFR2 pathway modulates amyloid pathology and neuroinflammation in Alzheimer's disease (2018). 2018. ↩︎
McCoy MK & Bhatt DG, TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease (2018). 2018. ↩︎
Arnett HA et al. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination (2001). 2001. ↩︎
Fischer R et al. Selective activation of tumor necrosis factor receptor II induces anti-inflammatory responses and reduces experimental arthritis (2018). 2018. ↩︎