Seroatlas · Human Serome Atlas

CD40

Tumor necrosis factor receptor superfamily member 5

Also known as: Bp50, p50, TNFRSF5, TNR5_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
P25942
Gene
CD40
Ensembl
ENSG00000101017
Chromosome
20
Canonical length
277 aa
Protein class
Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Predicted membrane proteins, Predicted secreted proteins
Subcellular location
Vesicles,Plasma membrane
Secretome location
Secreted to blood
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene is a member of the TNF-receptor superfamily. The encoded protein is a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency type 3 (HIGM3). Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2014]

Canonical amino-acid sequenceUniProt

277 residues, UniProt reviewed canonical sequence.

>P25942|CD40
     1  MVRLPLQCVL WGCLLTAVHP EPPTACREKQ YLINSQCCSL CQPGQKLVSD CTEFTETECL
    61  PCGESEFLDT WNRETHCHQH KYCDPNLGLR VQQKGTSETD TICTCEEGWH CTSEACESCV
   121  LHRSCSPGFG VKQIATGVSD TICEPCPVGF FSNVSSAFEK CHPWTSCETK DLVVQQAGTN
   181  KTDVVCGPQD RLRALVVIPI IFGILFAILL VLVFIKKVAK KPTNKAPHPK QEPQEINFPD
   241  DLPGSNTAAP VQETLHGCQP VTQEDGKESR ISVQERQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD40 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)
0.48
Highest tissue expression
53 nTPM

Expression across tissuesHPA

Tissue

  • tonsil: 53 nTPM
  • lymph node: 45 nTPM
  • parathyroid gland: 41 nTPM
  • urinary bladder: 30 nTPM
  • appendix: 27 nTPM
  • lung: 22 nTPM

Single-cell type

  • epididymal basal cells: 152 nCPM
  • cdc: 103 nCPM
  • b-cells: 101 nCPM
  • vascular endothelial cells: 62 nCPM
  • epididymal clear cells: 57 nCPM
  • fallopian secretory cells: 54 nCPM

Immune cell

  • naive B-cell: 124 nTPM
  • memory B-cell: 108 nTPM
  • intermediate monocyte: 35 nTPM
  • non-classical monocyte: 27 nTPM
  • classical monocyte: 23 nTPM
  • total PBMC: 15 nTPM

Brain region

  • choroid plexus: 6.7 nTPM
  • white matter: 3.7 nTPM
  • spinal cord: 3.2 nTPM
  • medulla oblongata: 3.1 nTPM
  • pons: 2.4 nTPM
  • hypothalamus: 2.3 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD40.

Disease | AllUniProt

Conditions CD40 is implicated in, by any mechanism.

  • Immunodeficiency with hyper-IgM 3 (HIGM3) MIM:606843

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 295 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Hyper-IgM syndrome type 3

Disease | AutoantibodyPubMed

Conditions in which antibodies against CD40 are reported. Each links to that disease's full target list.

ReferencesPubMed · IEDB

Publications for CD40 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

33 publications

Show 20 more of 33 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)
0.42
gnomAD pLI
0.85
gnomAD missense Z
1.41
DepMap mean gene effect
-0.02
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CD40 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 CD40 as an antibody target. Whether an autoantibody or antibody against CD40 could matter depends on whether native CD40 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CD40 is annotated at the cell surface, where native CD40 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 CD40 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CD40. 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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