TNFRSF12A

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TNFRSF12A is a small protein in the tumor necrosis factor receptor (TNFR) family. It is also known as the TWEAK receptor (TWEAKR) or FN14. The human gene sits on chromosome 16p13.3, and the mouse version is on chromosome 17; the human and mouse receptors are about 93% similar.

TNFRSF12A sits on the cell surface as a type I transmembrane protein and binds its ligand TWEAK. It has a cysteine-rich extracellular domain and does not have a death domain, but it can still transmit signals that influence inflammation, the growth of new blood vessels (angiogenesis), cell growth, and sometimes cell death. Its activity is tightly regulated both in living organisms and in laboratory settings.

This receptor is expressed in many tissues, including the heart, kidney, lung, pancreas, and skeletal muscle. Through FN14/TWEAK signaling, it can promote inflammatory responses and tissue remodeling. Abnormal TNFRSF12A signaling has been linked to diseases such as acute ischemic stroke, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and cancer. In animal studies, blocking TWEAK with antibodies reduced disease severity, suggesting TNFRSF12A could be a potential target or biomarker for cancer treatment.

TNFRSF12A also interacts with TRAF proteins (TRAF1, TRAF2, TRAF3, and TRAF5), which help relay signals inside the cell.