Seroatlas · Human Serome Atlas

TNFSF12

Tumor necrosis factor ligand superfamily member 12

Also known as: APO3L, DR3LG, TNF12_HUMAN, TWEAK

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O43508
Gene
TNFSF12
Ensembl
ENSG00000239697
Chromosome
17
Canonical length
249 aa
Protein class
Predicted intracellular proteins, Predicted secreted proteins
Subcellular location
Vesicles
Secretome location
Secreted to blood
Quaternary structure
Homotrimer

OverviewNCBI Gene

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, which exists in both membrane-bound and secreted forms, 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. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

Canonical amino-acid sequenceUniProt

249 residues, UniProt reviewed canonical sequence.

>O43508|TNFSF12
     1  MAARRSQRRR GRRGEPGTAL LVPLALGLGL ALACLGLLLA VVSLGSRASL SAQEPAQEEL
    61  VAEEDQDPSE LNPQTEESQD PAPFLNRLVR PRRSAPKGRK TRARRAIAAH YEVHPRPGQD
   121  GAQAGVDGTV SGWEEARINS SSPLRYNRQI GEFIVTRAGL YYLYCQVHFD EGKAVYLKLD
   181  LLVDGVLALR CLEEFSATAA SSLGPQLRLC QVSGLLALRP GSSLRIRTLP WAHLKAAPFL
   241  TYFGLFQVH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFSF12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.45
Highest tissue expression
103 nTPM

Expression across tissuesHPA

Tissue

  • blood vessel: 103 nTPM
  • colon: 84 nTPM
  • cerebral cortex: 65 nTPM
  • amygdala: 64 nTPM
  • urinary bladder: 60 nTPM
  • adipose tissue: 54 nTPM

Single-cell type

  • bergmann glia: 22 nCPM
  • microglia: 21 nCPM
  • oligodendrocyte progenitor cells: 14 nCPM
  • brain excitatory neurons: 12 nCPM
  • other brain neurons: 10 nCPM
  • astrocytes: 9.9 nCPM

Immune cell

  • eosinophil: 2.3 nTPM
  • gdT-cell: 1.7 nTPM
  • intermediate monocyte: 1.3 nTPM
  • naive CD8 T-cell: 1.3 nTPM
  • MAIT T-cell: 1.1 nTPM
  • memory CD8 T-cell: 0.9 nTPM

Brain region

  • thalamus: 45 nTPM
  • medulla oblongata: 44 nTPM
  • amygdala: 43 nTPM
  • cerebral cortex: 43 nTPM
  • midbrain: 36 nTPM
  • spinal cord: 36 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.41
gnomAD pLI
0.77
gnomAD missense Z
0.98
DepMap mean gene effect
-0.04
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TNFSF12 as an antibody target. Whether an autoantibody or antibody against TNFSF12 could matter depends on whether native TNFSF12 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TNFSF12 is annotated at the cell surface, where native TNFSF12 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label TNFSF12 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TNFSF12. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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