CD40LG

Protein identityUniProt · HPA

UniProt accession

P29965

Gene

CD40LG

Ensembl

ENSG00000102245

Chromosome

X

Canonical length

261 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus,Plasma membrane

Secretome location

Secreted to blood

Quaternary structure

Homotrimer

OverviewNCBI Gene

The protein encoded by this gene is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper-IgM syndrome. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

261 residues, UniProt reviewed canonical sequence.

>P29965|CD40LG
     1  MIETYNQTSP RSAATGLPIS MKIFMYLLTV FLITQMIGSA LFAVYLHRRL DKIEDERNLH
    61  EDFVFMKTIQ RCNTGERSLS LLNCEEIKSQ FEGFVKDIML NKEETKKENS FEMQKGDQNP
   121  QIAAHVISEA SSKTTSVLQW AEKGYYTMSN NLVTLENGKQ LTVKRQGLYY IYAQVTFCSN
   181  REASSQAPFI ASLCLKSPGR FERILLRAAN THSSAKPCGQ QSIHLGGVFE LQPGASVFVN
   241  VTDPSQVSHG TGFTSFGLLK L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD40LG 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

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD40LG.

Disease | AllUniProt

Conditions CD40LG is implicated in, by any mechanism.

• Immunodeficiency with hyper-IgM, type 1 (HIGM1) MIM:308230

Disease | GeneticClinVar

104 pathogenic / likely-pathogenic of 338 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyper-IgM syndrome type 1
• Inborn genetic diseases
• Common variable immunodeficiency
• Hyperimmunoglobulin M syndrome
• Nonpapillary renal cell carcinoma

Disease | AutoantibodyPubMed

Conditions in which antibodies against CD40LG are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 17
• Lupus Nephritis 8
• Purpura, Thrombocytopenic, Idiopathic 5
• Diabetes Mellitus, Type 1 4
• Glomerulonephritis 3
• Proteinuria 3

ReferencesPubMed · IEDB

Publications for CD40LG 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.

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)

0.56

gnomAD pLI

0.72

gnomAD missense Z

1.3

DepMap mean gene effect

0.09

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

• B cell differentiation
• B cell proliferation
• CD40 signaling pathway
• cell surface receptor signaling pathway
• inflammatory response
• integrin-mediated signaling pathway
• isotype switching
• leukocyte cell-cell adhesion
• negative regulation of apoptotic process
• platelet activation
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of endothelial cell apoptotic process
• positive regulation of extrinsic apoptotic signaling pathway
• positive regulation of interleukin-10 production
• positive regulation of interleukin-12 production
• positive regulation of interleukin-4 production
• positive regulation of NF-kappaB transcription factor activity
• positive regulation of T cell proliferation
• regulation of immunoglobulin production
• T cell costimulation

Molecular functions

• CD40 receptor binding
• cytokine activity
• integrin binding
• protein serine/threonine kinase activator activity
• tumor necrosis factor receptor binding

Cellular components

• cell surface
• external side of plasma membrane
• extracellular space
• Golgi apparatus
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Tumour necrosis factor domain
• Tumour necrosis factor-like domain superfamily
• Tumour necrosis factor, conserved site
• TNF(Tumour Necrosis Factor) family
• CD40 ligand

KeywordsUniProt

• Cell membrane
• Cytokine
• Disulfide bond
• Glycoprotein
• Membrane
• Secreted
• Signal-anchor
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CD40LG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD28