Seroatlas · Human Serome Atlas

TNF

Tumor necrosis factor

Also known as: DIF, TNF-alpha, TNFA, TNFA_HUMAN, TNFSF2

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

Protein identityUniProt · HPA

UniProt accession
P01375
Gene
TNF
Ensembl
ENSG00000232810
Chromosome
6
Canonical length
233 aa
Protein class
Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
Secretome location
Secreted to blood
Quaternary structure
Homotrimer

OverviewNCBI Gene

This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

233 residues, UniProt reviewed canonical sequence.

>P01375|TNF
     1  MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR
    61  EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR
   121  DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE
   181  TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNF 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)
0.4
Highest tissue expression
20 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 20 nTPM
  • spleen: 6.1 nTPM
  • lymph node: 4.2 nTPM
  • appendix: 4 nTPM
  • lung: 3.4 nTPM
  • heart muscle: 2.7 nTPM

Single-cell type

  • microglia: 7.8 nCPM
  • nk-cells: 1.4 nCPM
  • t-cells: 1.3 nCPM
  • loop of henle epithelial cells: 1.2 nCPM
  • monocytes: 1 nCPM
  • proximal tubule cells: 1 nCPM

Immune cell

  • non-classical monocyte: 73 nTPM
  • intermediate monocyte: 42 nTPM
  • MAIT T-cell: 41 nTPM
  • gdT-cell: 26 nTPM
  • neutrophil: 23 nTPM
  • memory CD4 T-cell: 20 nTPM

Brain region

  • choroid plexus: 1.1 nTPM
  • cerebellum: 0.5 nTPM
  • cerebral cortex: 0.5 nTPM
  • pons: 0.5 nTPM
  • hippocampal formation: 0.4 nTPM
  • thalamus: 0.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNF.

Disease | AllUniProt

Conditions TNF is implicated in, by any mechanism.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 24 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • TNF receptor binding, altered

Disease | AutoantibodyPubMed

Conditions in which antibodies against TNF are reported. Each links to that disease's full target list.

Showing 10 of 12 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for TNF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

126 publications

Show 20 more of 126 total

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)
0.49
gnomAD pLI
0.8
gnomAD missense Z
1.62
DepMap mean gene effect
-0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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

InteractionsUniProt · HPA

Protein binding partners of TNF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

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

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

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

  • This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer.

Canonical record: https://seroatlas.com/gene/TNF. 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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