TNFSF12 gene

The TNFSF12 gene (TNFSF12 stands for: TNF Superfamily Member 12) is a protein-coding gene located on chromosome 17p13.1. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene.

The protein encoded by the TNFSF12 gene is a cytokine that belongs to the family of tumor necrosis factor (TNF) ligands. This protein is a ligand for the FN14/TWEAKR receptor. An important paralog of this gene is TNFSF13B. Alternative splicing leads to several transcript variants.

The TWEAK protein is a cytokine that has overlapping signaling functions with TNF, but has a much broader tissue distribution. The TWEAK cytokine occurs both in membrane-bound and secreted form. It can trigger apoptosis via several cell death pathways in a cell type-specific manner. It also promotes the proliferation and migration of endothelial cells and thus acts as a regulator of angiogenesis. Binds to FN14 and possibly also to TNRFSF12/APO3. The cytokine is a weak trigger of apoptosis in some cell types. It mediates the activation of NF-kappa-B. Promotes angiogenesis and proliferation of endothelial cells and is involved in the induction of inflammatory cytokines, including IL8.

Diseases associated with TNFSF12 include:

Common variable immunodeficiency(CVID). CVID includes a group of diseases characterized by low levels of immunoglobulins (Ig), resulting in an inability to produce antibodies to fight infections. Symptoms include susceptibility to bacterial infections, particularly in the sinuses, lungs and digestive tract. CVID can occur at any age, and genetic changes are found in about a third of cases. The diagnosis of CVID is based on clinical symptoms, laboratory tests and the exclusion of other diseases.)

and

Amnestic disorders.

Related signaling pathways include MIF-mediated glucocorticoid regulation and the TNFR1 signaling pathway.

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