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Tumor necrosis factor (ligand) superfamily, member 12
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM602695 MGI1196259 HomoloGene7979 GeneCards: TNFSF12 Gene
Species Human Mouse
Entrez 8742 21944
Ensembl ENSG00000239697 ENSMUSG00000097328
UniProt O43508 O54907
RefSeq (mRNA) NM_003809 NM_011614
RefSeq (protein) NP_003800 NP_035744
Location (UCSC) Chr 17:
7.45 – 7.46 Mb
Chr 11:
69.68 – 69.7 Mb
PubMed search [1] [2]

Tumor necrosis factor ligand superfamily member 12 also known as TNF-related weak inducer of apoptosis (TWEAK) is a protein that in humans is encoded by the TNFSF12 gene.[1][2][3]


The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis.[3]

Clinical signficance[edit]

NFAT1 regulates the expression of TWEAKR and its ligand TWEAK (this protein) with lipocalin 2 to increase breast cancer cell invasion.[4]


  1. ^ Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, Garcia I, Browning JL (Jan 1998). "TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis". J Biol Chem 272 (51): 32401–10. doi:10.1074/jbc.272.51.32401. PMID 9405449. 
  2. ^ Marsters SA, Sheridan JP, Pitti RM, Brush J, Goddard A, Ashkenazi A (Aug 1998). "Identification of a ligand for the death-domain-containing receptor Apo3". Curr Biol 8 (9): 525–8. doi:10.1016/S0960-9822(98)70204-0. PMID 9560343. 
  3. ^ a b "Entrez Gene: TNFSF12 tumor necrosis factor (ligand) superfamily, member 12". 
  4. ^ Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S (October 2012). "Lipocalin 2, the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion". J. Cell. Sci. 125 (Pt 19): 4475–86. doi:10.1242/jcs.099879. PMID 22767506. 

Further reading[edit]