Seroatlas · Human Serome Atlas

TNFRSF21

Tumor necrosis factor receptor superfamily member 21

Also known as: CD358, DR6, TNR21_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
O75509
Gene
TNFRSF21
Ensembl
ENSG00000146072
Chromosome
6
Canonical length
655 aa
Protein class
CD markers, Plasma proteins, Predicted membrane proteins
Subcellular location
Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]

Canonical amino-acid sequenceUniProt

655 residues, UniProt reviewed canonical sequence.

>O75509|TNFRSF21
     1  MGTSPSSSTA LASCSRIARR ATATMIAGSL LLLGFLSTTT AQPEQKASNL IGTYRHVDRA
    61  TGQVLTCDKC PAGTYVSEHC TNTSLRVCSS CPVGTFTRHE NGIEKCHDCS QPCPWPMIEK
   121  LPCAALTDRE CTCPPGMFQS NATCAPHTVC PVGWGVRKKG TETEDVRCKQ CARGTFSDVP
   181  SSVMKCKAYT DCLSQNLVVI KPGTKETDNV CGTLPSFSSS TSPSPGTAIF PRPEHMETHE
   241  VPSSTYVPKG MNSTESNSSA SVRPKVLSSI QEGTVPDNTS SARGKEDVNK TLPNLQVVNH
   301  QQGPHHRHIL KLLPSMEATG GEKSSTPIKG PKRGHPRQNL HKHFDINEHL PWMIVLFLLL
   361  VLVVIVVCSI RKSSRTLKKG PRQDPSAIVE KAGLKKSMTP TQNREKWIYY CNGHGIDILK
   421  LVAAQVGSQW KDIYQFLCNA SEREVAAFSN GYTADHERAY AALQHWTIRG PEASLAQLIS
   481  ALRQHRRNDV VEKIRGLMED TTQLETDKLA LPMSPSPLSP SPIPSPNAKL ENSALLTVEP
   541  SPQDKNKGFF VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF
   601  DDMLHFLNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH LPDLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFRSF21 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)
0.5
Highest tissue expression
138 nTPM

Expression across tissuesHPA

Tissue

  • urinary bladder: 138 nTPM
  • spinal cord: 109 nTPM
  • stomach: 57 nTPM
  • parathyroid gland: 55 nTPM
  • adipose tissue: 52 nTPM
  • kidney: 46 nTPM

Single-cell type

  • urothelial cells: 982 nCPM
  • papillary tip epithelial cells: 359 nCPM
  • prostatic club cells: 339 nCPM
  • ocular epithelial cells: 323 nCPM
  • syncytiotrophoblasts: 275 nCPM
  • kupffer cells: 237 nCPM

Immune cell

  • plasmacytoid DC: 69 nTPM
  • myeloid DC: 1.9 nTPM
  • total PBMC: 0.6 nTPM
  • eosinophil: 0.2 nTPM
  • classical monocyte: 0.1 nTPM
  • naive B-cell: 0.1 nTPM

Brain region

  • white matter: 217 nTPM
  • medulla oblongata: 172 nTPM
  • pons: 126 nTPM
  • cerebellum: 113 nTPM
  • thalamus: 113 nTPM
  • spinal cord: 104 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)
0.61
gnomAD pLI
0.04
gnomAD missense Z
1.22
DepMap mean gene effect
0.07
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TNFRSF21 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 TNFRSF21 as an antibody target. Whether an autoantibody or antibody against TNFRSF21 could matter depends on whether native TNFRSF21 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TNFRSF21 is annotated at the cell surface, where native TNFRSF21 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 TNFRSF21 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TNFRSF21. 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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