Human Gene CD40LG (ENST00000370629.7) from GENCODE V44
  Description: Homo sapiens CD40 ligand (CD40LG), mRNA. (from RefSeq NM_000074)
RefSeq Summary (NM_000074): 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].
Gencode Transcript: ENST00000370629.7
Gencode Gene: ENSG00000102245.9
Transcript (Including UTRs)
   Position: hg38 chrX:136,648,158-136,660,390 Size: 12,233 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg38 chrX:136,648,249-136,659,415 Size: 11,167 Coding Exon Count: 5 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:136,648,158-136,660,390)mRNA (may differ from genome)Protein (261 aa)
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-  Comments and Description Text from UniProtKB
  ID: CD40L_HUMAN
DESCRIPTION: RecName: Full=CD40 ligand; Short=CD40-L; AltName: Full=T-cell antigen Gp39; AltName: Full=TNF-related activation protein; Short=TRAP; AltName: Full=Tumor necrosis factor ligand superfamily member 5; AltName: CD_antigen=CD154; Contains: RecName: Full=CD40 ligand, membrane form; Contains: RecName: Full=CD40 ligand, soluble form;
FUNCTION: Mediates B-cell proliferation in the absence of co- stimulus as well as IgE production in the presence of IL-4. Involved in immunoglobulin class switching.
FUNCTION: Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.
SUBUNIT: Homotrimer.
SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.
SUBCELLULAR LOCATION: CD40 ligand, soluble form: Secreted.
TISSUE SPECIFICITY: Specifically expressed on activated CD4+ T- lymphocytes.
PTM: The soluble form derives from the membrane form by proteolytic processing.
PTM: N-linked glycan is a mixture of high mannose and complex type. Glycan structure does not influence binding affinity to CD40.
PTM: Not O-glycosylated.
DISEASE: Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:308230]; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.
SIMILARITY: Belongs to the tumor necrosis factor family.
WEB RESOURCE: Name=CD40Lbase; Note=CD40L defect database; URL="http://bioinf.uta.fi/CD40Lbase/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CD40LG";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: CD40LG
Diseases sorted by gene-association score: immunodeficiency, x-linked, with hyper-igm* (1571), cd40 ligand deficiency* (532), toxoplasmosis (44), rubella (42), pneumonia (35), cryoglobulinemia (34), congenital toxoplasmosis (33), hepatitis e (33), congenital syphilis (31), hemorrhagic fever with renal syndrome (25), q fever (25), meningoencephalitis (25), persistent generalized lymphadenopathy (24), secondary syphilis (24), erythema infectiosum (24), lyme disease (24), african tick-bite fever (23), acrodermatitis chronica atrophicans (23), waldenstrom macroglobulinemia (20), coccidiosis (19), macroglobulinemia (19), syphilis (19), exanthem (18), immunoglobulin alpha deficiency (18), myocarditis (18), iga glomerulonephritis (18), episodic angioedema with eosinophilia (18), dengue disease (18), autoimmune disease of blood (18), viral exanthem (18), antiphospholipid syndrome (18), cryofibrinogenemia (18), c1q nephropathy (18), brucellosis (17), leptospirosis (17), bartonellosis (17), scrub typhus (17), hemorrhagic fever (17), parotid disease (17), phlebotomus fever (16), cryptosporidiosis (16), pelvic inflammatory disease (16), primary immunodeficiency disease (16), epidemic typhus (16), systemic lupus erythematosus (16), monoclonal paraproteinemia (16), neuroretinitis (15), early congenital syphilis (15), systemic scleroderma (15), sporotrichosis (15), lymphoplasmacytic lymphoma (14), loeffler syndrome (14), colorado tick fever (14), epidemic pleurodynia (14), spastic monoplegia (14), viral labyrinthitis (14), benign mastocytoma (14), acute hemorrhagic encephalitis (14), ross river fever (14), legionellosis (14), basidiobolomycosis (14), hepatitis d (14), temporal arteritis (14), primary bacterial infectious disease (14), immunodeficiency with hyper-igm, type 3 (14), kidney leiomyosarcoma (14), schistosomiasis (13), heparin-induced thrombocytopenia (13), parasitic protozoa infectious disease (13), plasma protein metabolism disease (13), multifocal motor neuropathy (13), mumps (13), hyperimmunoglobulin syndrome (12), congenital rubella (12), vasomotor rhinitis (12), primary biliary cirrhosis (12), selective iga deficiency disease (12), cat-scratch disease (12), tetanus (12), hypersensitivity reaction type iii disease (12), miller fisher syndrome (12), echinococcosis (11), selective immunoglobulin deficiency disease (11), west nile fever (11), pfeiffer syndrome (11), agammaglobulinemia (11), tertiary syphilis (11), chronic polyneuropathy (11), diarrhea (11), subacute bacterial endocarditis (11), exanthema subitum (11), marginal zone b-cell lymphoma (11), fallopian tube disease (11), ornithosis (11), guillain-barre syndrome (11), brill-zinsser disease (11), immunoglobulin g deficiency (11), immune defect due to absence of thymus (11), zika fever (10), kyasanur forest disease (10), rheumatic fever (10), hypersensitivity reaction type iv disease (10), hydrops of gallbladder (10), granulomatous hepatitis (10), gastroduodenitis (10), cerebral arteritis (10), cryoglobulinemia, familial mixed (10), crest syndrome (10), common variable immunodeficiency (10), schnitzler syndrome (10), vasculitis (10), immune system disease (10), primary thrombocytopenia (10), indian tick typhus (10), herpetic whitlow (10), mixed connective tissue disease (10), exudative glomerulonephritis (10), chorioretinitis (10), hypersensitivity reaction disease (10), selective igg deficiency disease (10), commensal bacterial infectious disease (10), primary syphilis (10), facial nerve disease (10), cork-handlers' disease (10), autoimmune hemolytic anemia (10), pulmonary embolism and infarction (10), purpura (10), latent syphilis (9), capillariasis (9), dermatitis herpetiformis (9), viral infectious disease (9), salivary gland disease (9), polyneuropathy (9), plasmodium vivax malaria (9), alpha chain disease (9), autoimmune hepatitis (9), hypersensitivity reaction type ii disease (9), secondary progressive multiple sclerosis (9), middle cerebral artery infarction (9), connective tissue disease (9), progressive multifocal leukoencephalopathy (9), bacteriuria (9), mononeuritis of upper limb and mononeuritis multiplex (9), salpingitis (9), immunodeficiency with hyper-igm, type 2 (9), acute salpingitis (9), plasma cell neoplasm (9), chlamydia (9), indeterminate leprosy (9), cystic echinococcosis (9), asymptomatic neurosyphilis (9), glomerulonephritis (9), measles (8), aleutian mink disease (8), optic papillitis (8), pontiac fever (8), plasmodium malariae malaria (8), post-vaccinal encephalitis (8), transient arthritis (8), facial paralysis (8), focal chorioretinitis (8), geniculate herpes zoster (8), middle ear disease (8), meningovascular neurosyphilis (8), salpingo-oophoritis (8), toxocariasis (8), retinitis pigmentosa 48 (8), louping ill (8), rheumatoid lung disease (8), burkitt lymphoma (8), granulomatous gastritis (8), cutaneous lupus erythematosus (8), polyclonal hypergammaglobulinemia (8), chickenpox (8), autoimmune disease of urogenital tract (8), neuronitis (8), rabies (8), mature b-cell neoplasm (8), axillary adenitis (8), cardiovascular syphilis (8), monoclonal gammopathy of uncertain significance (8), eosinophilic meningitis (8), oropouche fever (8), trench fever (8), la crosse encephalitis (8), mononeuritis multiplex (8), orbital granuloma (8), endocrine exophthalmos (8), trichostrongyloidiasis (8), taeniasis (8), splenic disease (8), flinders island spotted fever (8), lassa fever (8), trichostrongylosis (8), osteosclerotic myeloma (8), viral hepatitis (8), rocky mountain spotted fever (7), meningitis (7), tertiary neurosyphilis (7), murray valley encephalitis (7), fournier gangrene (7), lung lymphoma (7), acalculous cholecystitis (7), livedoid vasculopathy (7), spinal cord disease (7), ocular toxoplasmosis (7), dysgammaglobulinemia (7), hypersensitivity vasculitis (7), japanese spotted fever (7), intussusception (7), ophthalmia neonatorum (7), diffuse glomerulonephritis (7), coccidioidomycosis (7), acquired immunodeficiency syndrome (7), spondyloarthropathy 1 (7), demyelinating disease (7), churg-strauss syndrome (7), cholangitis (7), mononeuropathy (7), transient hypogammaglobulinemia of infancy (7), evans' syndrome (7), inclusion conjunctivitis (7), leprosy (7), syphilitic meningitis (7), multiple sclerosis, disease progression, modifier of (7), extrinsic cardiomyopathy (7), early yaws (7), borderline leprosy (7), sclerosing cholangitis (7), chronic interstitial cystitis (7), otitis media (7), ventilation pneumonitis (7), b cell deficiency (7), fasciolopsiasis (7), acute retinal necrosis syndrome (7), lupus erythematosus (7), thrombocytopenia due to platelet alloimmunization (7), pericardium disease (7), non-secretory myeloma (7), erythema elevatum diutinum (7), legg-calve-perthes disease (7), pneumocystosis (6), encephalitozoonosis (6), heavy chain disease (6), periodontosis (6), pulmonary hemosiderosis (6), acrodermatitis (6), immunodeficiency with hyper-igm, type 4 (6), pustulosis palmaris et plantaris (6), endocardium disease (6), conjunctival disease (6), iridocyclitis (6), hemolytic-uremic syndrome (6), tolosa-hunt syndrome (6), dengue hemorrhagic fever (6), primary systemic mycosis (6), immunodeficiency-centromeric instability-facial anomalies syndrome (6), catastrophic antiphospholipid syndrome (6), rheumatic disease (6), takayasu arteritis (6), severe acute respiratory syndrome (6), bacterial conjunctivitis (6), heterophyiasis (6), chorioretinal scar (6), urethritis (6), sickle cell anemia (6), myasthenic syndrome, congenital, 10 (6), bronchitis (6), necrotizing ulcerative gingivitis (6), congenital hypogammaglobulinemia (6), buruli ulcer (6), korean hemorrhagic fever (6), cd3gamma deficiency (6), norwegian scabies (6), rift valley fever (6), parasitic ichthyosporea infectious disease (6), rhinosporidiosis (6), iritis (6), yellow nail syndrome (5), parasitic helminthiasis infectious disease (5), bronchopneumonia (5), central nervous system vasculitis (5), acute proliferative glomerulonephritis (5), spinocerebellar ataxia, autosomal recessive 10 (5), chronic lymphocytic leukemia (5), malaria (5), henoch-schoenlein purpura (5), bone inflammation disease (5), hyperglobulinemic purpura (5), panencephalitis, subacute sclerosing (5), peripheral nervous system disease (5), giardiasis (5), suppurative otitis media (5), autoimmune disease of gastrointestinal tract (5), lichen disease (5), functional colonic disease (5), gray platelet syndrome (5), chikungunya (5), human granulocytic anaplasmosis (5), spondylitis (5), facial hemiatrophy (5), amebiasis (5), asthma (5), ancylostomiasis (5), leukocyte disease (5), dressler's syndrome (5), intestinal schistosomiasis (5), brachial plexus neuritis (5), ehrlichiosis (5), lymph node disease (5), gamma heavy chain disease (5), human immunodeficiency virus infectious disease (5), cervix disease (5), dirofilariasis (5), panuveitis (5), opportunistic mycosis (5), legionnaires' disease (5), acute maxillary sinusitis (5), urethral syndrome (5), autoimmune disease of skin and connective tissue (5), colonic pseudo-obstruction (5), acrocallosal syndrome (5), blood coagulation disease (4), caffey disease (4), idiopathic neutropenia (4), hemorrhagic disease (4), jejunoileitis (4), vulvitis (4), branch retinal artery occlusion (4), pyelitis (4), byssinosis (4), dysentery (4), streptococcal meningitis (4), cogan syndrome (4), lymphatic system disease (4), lymphoproliferative syndrome 2 (4), carrion's disease (4), combined t cell and b cell immunodeficiency (4), thymic dysplasia (4), critical illness polyneuropathy (4), herpes gestationis (4), multiple cranial nerve palsy (4), chronic salpingitis (3), pleuropneumonia (3), vernal conjunctivitis (3), rheumatoid arthritis (3), bronchiolitis (3), celiac disease (2), mantle cell lymphoma (2), multiple myeloma (2), gastrointestinal system disease (2), blood platelet disease (2), respiratory system disease (2), urinary system disease (2), nervous system disease (1), rheumatoid arthritis, systemic juvenile (1), upper respiratory tract disease (1), myocardial infarction (1), lymphoma, malt, somatic (1), lymphoma, non-hodgkin (1), behcet syndrome (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.55 RPKM in Spleen
Total median expression: 13.85 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -18.7091-0.205 Picture PostScript Text
3' UTR -222.60975-0.228 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006052 - TNF
IPR021184 - TNF_CS
IPR003263 - TNF_ligand_5
IPR008983 - Tumour_necrosis_fac-like

Pfam Domains:
PF00229 - TNF(Tumour Necrosis Factor) family

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1ALY - X-ray MuPIT 1I9R - X-ray MuPIT 3LKJ - X-ray MuPIT 3QD6 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P29965
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005125 cytokine activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005174 CD40 receptor binding
GO:0005515 protein binding

Biological Process:
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007159 leukocyte cell-cell adhesion
GO:0007257 activation of JUN kinase activity
GO:0010469 regulation of receptor activity
GO:0030168 platelet activation
GO:0030183 B cell differentiation
GO:0031295 T cell costimulation
GO:0032733 positive regulation of interleukin-10 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032753 positive regulation of interleukin-4 production
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0042100 B cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0043066 negative regulation of apoptotic process
GO:0045190 isotype switching
GO:0048305 immunoglobulin secretion
GO:0050776 regulation of immune response
GO:0051023 regulation of immunoglobulin secretion
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:2000353 positive regulation of endothelial cell apoptotic process

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  BC071754 - Homo sapiens CD40 ligand, mRNA (cDNA clone MGC:88303 IMAGE:30418744), complete cds.
AK292637 - Homo sapiens cDNA FLJ75817 complete cds, highly similar to Homo sapiens CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome) (CD40LG), mRNA.
X68550 - H.sapiens TRAP mRNA for ligand of CD40.
X67878 - H.sapiens mRNA for CD40 ligand.
L07414 - Homo sapiens CD40 surface protein mRNA, complete cds.
BC074950 - Homo sapiens CD40 ligand, mRNA (cDNA clone MGC:103892 IMAGE:30915276), complete cds.
X96710 - H.sapiens mRNA for CD40-ligand.
Z15017 - H.sapiens mRNA for glycoprotein 39 (gp39).
JD166274 - Sequence 147298 from Patent EP1572962.
FN298241 - Homo sapiens mRNA for CD40 ligand (CD40LG gene).
CU687160 - Synthetic construct Homo sapiens gateway clone IMAGE:100023106 5' read CD40LG mRNA.
HQ447532 - Synthetic construct Homo sapiens clone IMAGE:100070871; CCSB014894_03 CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome) (CD40LG) gene, encodes complete protein.
AB590912 - Synthetic construct DNA, clone: pFN21AE1756, Homo sapiens CD40LG gene for CD40 ligand, without stop codon, in Flexi system.
AF529195 - Homo sapiens mutant CD154 mRNA, complete cds.
AY197739 - Homo sapiens CD154 protein (TNFSF5) mRNA, complete cds.
S66178 - CD40 ligand {58 bp deletion between residues 288-289} [human, HIGMX-1 patient, peripheral blood mononuclear cells, mRNA PartialMutant, 64 nt].
JD241676 - Sequence 222700 from Patent EP1572962.
JD148783 - Sequence 129807 from Patent EP1572962.
JD080753 - Sequence 61777 from Patent EP1572962.
JD263397 - Sequence 244421 from Patent EP1572962.
JD353413 - Sequence 334437 from Patent EP1572962.
JD119967 - Sequence 100991 from Patent EP1572962.
JD495023 - Sequence 476047 from Patent EP1572962.
JD314056 - Sequence 295080 from Patent EP1572962.
JD418792 - Sequence 399816 from Patent EP1572962.
JD298770 - Sequence 279794 from Patent EP1572962.
JD566112 - Sequence 547136 from Patent EP1572962.
JD153922 - Sequence 134946 from Patent EP1572962.
JD528826 - Sequence 509850 from Patent EP1572962.
JD261633 - Sequence 242657 from Patent EP1572962.
JD229549 - Sequence 210573 from Patent EP1572962.
JD392513 - Sequence 373537 from Patent EP1572962.
JD048083 - Sequence 29107 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04060 - Cytokine-cytokine receptor interaction
hsa04514 - Cell adhesion molecules (CAMs)
hsa04660 - T cell receptor signaling pathway
hsa04672 - Intestinal immune network for IgA production
hsa05310 - Asthma
hsa05320 - Autoimmune thyroid disease
hsa05322 - Systemic lupus erythematosus
hsa05330 - Allograft rejection
hsa05340 - Primary immunodeficiency
hsa05416 - Viral myocarditis

BioCarta from NCI Cancer Genome Anatomy Project
h_asbcellPathway - Antigen Dependent B Cell Activation
h_cd40Pathway - CD40L Signaling Pathway
h_th1th2Pathway - Th1/Th2 Differentiation
h_bbcellPathway - Bystander B Cell Activation
h_nktPathway - Selective expression of chemokine receptors during T-cell polarization

Reactome (by CSHL, EBI, and GO)

Protein P29965 (Reactome details) participates in the following event(s):

R-HSA-199404 CD40L binds CD40
R-HSA-5676597 TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds CD40
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-1280218 Adaptive Immune System
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-168256 Immune System
R-HSA-1280215 Cytokine Signaling in Immune system

-  Other Names for This Gene
  Alternate Gene Symbols: CD40L, CD40L_HUMAN, ENST00000370629.1, ENST00000370629.2, ENST00000370629.3, ENST00000370629.4, ENST00000370629.5, ENST00000370629.6, NM_000074, P29965, TNFSF5, TRAP, uc004faa.1, uc004faa.2, uc004faa.3, uc004faa.4, uc004faa.5
UCSC ID: ENST00000370629.7
RefSeq Accession: NM_000074
Protein: P29965 (aka CD40L_HUMAN)
CCDS: CCDS14659.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CD40LG:
xlhi (X-Linked Hyper IgM Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.