Seroatlas · Human Serome Atlas

TNFRSF4

Tumor necrosis factor receptor superfamily member 4

Also known as: ACT35, CD134, OX40, TNR4_HUMAN, TXGP1L

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

Protein identityUniProt · HPA

UniProt accession
P43489
Gene
TNFRSF4
Ensembl
ENSG00000186827
Chromosome
1
Canonical length
277 aa
Protein class
Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. Knockout studies in mice suggested that this receptor promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. The knockout studies also suggested the roles of this receptor in CD4+ T cell response, as well as in T cell-dependent B cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

277 residues, UniProt reviewed canonical sequence.

>P43489|TNFRSF4
     1  MCVGARRLGR GPCAALLLLG LGLSTVTGLH CVGDTYPSND RCCHECRPGN GMVSRCSRSQ
    61  NTVCRPCGPG FYNDVVSSKP CKPCTWCNLR SGSERKQLCT ATQDTVCRCR AGTQPLDSYK
   121  PGVDCAPCPP GHFSPGDNQA CKPWTNCTLA GKHTLQPASN SSDAICEDRD PPATQPQETQ
   181  GPPARPITVQ PTEAWPRTSQ GPSTRPVEVP GGRAVAAILG LGLVLGLLGP LAILLALYLL
   241  RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFRSF4 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)
0.53
Highest tissue expression
13 nTPM

Expression across tissuesHPA

Tissue

  • spleen: 13 nTPM
  • heart muscle: 10 nTPM
  • adipose tissue: 9.6 nTPM
  • breast: 6.3 nTPM
  • lung: 6.2 nTPM
  • lymph node: 5.5 nTPM

Single-cell type

  • innate lymphoid cells: 127 nCPM
  • plasma cells: 86 nCPM
  • mast cells: 50 nCPM
  • cdc: 41 nCPM
  • t-cells: 35 nCPM
  • thymocytes: 31 nCPM

Immune cell

  • T-reg: 31 nTPM
  • memory CD4 T-cell: 26 nTPM
  • NK-cell: 5.3 nTPM
  • total PBMC: 2.7 nTPM
  • MAIT T-cell: 2.4 nTPM
  • naive CD4 T-cell: 2.3 nTPM

Brain region

  • cerebellum: 2 nTPM
  • cerebral cortex: 1.4 nTPM
  • hippocampal formation: 1.4 nTPM
  • amygdala: 1 nTPM
  • thalamus: 1 nTPM
  • white matter: 1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNFRSF4.

Disease | AllUniProt

Conditions TNFRSF4 is implicated in, by any mechanism.

ReferencesPubMed · IEDB

Publications for TNFRSF4 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

9 publications

Show 4 more

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)
1.32
gnomAD pLI
0
gnomAD missense Z
0.62
DepMap mean gene effect
-0.01
DepMap dependency class
selective

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

InteractionsUniProt · HPA

Protein binding partners of TNFRSF4 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 TNFRSF4 as an antibody target. Whether an autoantibody or antibody against TNFRSF4 could matter depends on whether native TNFRSF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TNFRSF4 is annotated at the cell surface, where native TNFRSF4 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 TNFRSF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TNFRSF4. 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).

© 2026 · Seroatlas, Discover Oregon LLC · Terms of use

Loading the interactive Seroatlas protein explorer...