CD40

Summary

CD40 (CD40 molecule, HGNC:11919) is a protein-coding gene on chromosome 20q13.12, encoding Tumor necrosis factor receptor superfamily member 5 (P25942). Receptor for TNFSF5/CD40LG.

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.

Source: NCBI Gene 958 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyper-IgM syndrome type 3 (Definitive, ClinGen)
• GWAS associations: 27
• Clinical variants (ClinVar): 297 total — 13 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• MANE Select transcript: NM_001250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11919
Approved symbol	CD40
Name	CD40 molecule
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	p50, Bp50
Ensembl gene	ENSG00000101017
Ensembl biotype	protein_coding
OMIM	109535
Entrez	958

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000372276, ENST00000372285, ENST00000461171, ENST00000466205, ENST00000477696, ENST00000489304, ENST00000620709, ENST00000695669, ENST00000695670, ENST00000695671, ENST00000695672, ENST00000695673, ENST00000695674, ENST00000695675, ENST00000890861, ENST00000890862, ENST00000890863, ENST00000890864, ENST00000890865, ENST00000890866, ENST00000890867, ENST00000890868, ENST00000936297, ENST00000936298, ENST00000946602

RefSeq mRNA: 7 — MANE Select: NM_001250 NM_001250, NM_001302753, NM_001322421, NM_001322422, NM_001362758, NM_001424339, NM_152854

CCDS: CCDS13393, CCDS13394, CCDS93053

Canonical transcript exons

ENST00000372285 — 9 exons

Exon	Start	End
ENSE00003463300	46123126	46123219
ENSE00003474592	46128882	46129858
ENSE00003553589	46122610	46122756
ENSE00003616236	46121820	46121898
ENSE00003666903	46128330	46128358
ENSE00003673198	46122233	46122358
ENSE00003964679	46128138	46128224
ENSE00003964681	46118314	46118394
ENSE00003964691	46126640	46126701

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3047 / max 816.7242, expressed in 1148 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185054	16.3940	814
185053	2.3086	821
185052	1.4792	724
185055	0.1230	46

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	94.04	gold quality
right lung	UBERON:0002167	92.19	gold quality
spleen	UBERON:0002106	92.18	gold quality
upper lobe of left lung	UBERON:0008952	92.04	gold quality
left ovary	UBERON:0002119	91.97	gold quality
descending thoracic aorta	UBERON:0002345	91.61	gold quality
right ovary	UBERON:0002118	91.54	gold quality
vermiform appendix	UBERON:0001154	91.53	gold quality
mucosa of stomach	UBERON:0001199	91.24	gold quality
omental fat pad	UBERON:0010414	91.24	gold quality
peritoneum	UBERON:0002358	91.17	gold quality
upper lobe of lung	UBERON:0008948	90.94	gold quality
thoracic aorta	UBERON:0001515	90.81	gold quality
ascending aorta	UBERON:0001496	90.79	gold quality
granulocyte	CL:0000094	90.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.46	gold quality
right coronary artery	UBERON:0001625	90.28	gold quality
left coronary artery	UBERON:0001626	90.21	gold quality
pancreatic ductal cell	CL:0002079	89.97	gold quality
body of pancreas	UBERON:0001150	89.80	gold quality
coronary artery	UBERON:0001621	89.06	gold quality
body of uterus	UBERON:0009853	88.93	gold quality
endocervix	UBERON:0000458	88.86	gold quality
left uterine tube	UBERON:0001303	88.83	gold quality
parotid gland	UBERON:0001831	88.80	gold quality
tonsil	UBERON:0002372	88.66	gold quality
apex of heart	UBERON:0002098	88.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.46	gold quality
right lobe of thyroid gland	UBERON:0001119	88.33	gold quality
left lobe of thyroid gland	UBERON:0001120	88.33	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	94.24
E-GEOD-81383	yes	76.11
E-HCAD-13	yes	22.99
E-MTAB-9467	yes	21.03
E-CURD-112	yes	11.06
E-MTAB-6678	yes	7.11
E-ENAD-27	yes	4.03
E-MTAB-2983	no	729.18
E-MTAB-8498	no	575.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BCL2L1	Activation
BIK	Activation

Upstream regulators (CollecTRI, top): AHR, AKNA, AP1, CLEC7A, CUX1, FOXO1, IRF1, IRF6, JDP2, MITF, MYC, NFATC1, NFATC2, NFKB1, NFKB2, NFKB, NFKBIA, NR3C2, PAX6, PPARG, PRDM1, PTPN22, RBPJ, REL, RELA, RELB, SP1, SPI1, SPIB, STAT1, STAT6, TFE3, TFEC, THRA, TP53, TRAF6, TRERF1, USF1, USF2, XRCC5

miRNA regulators (miRDB)

38 targeting CD40, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-6893-3P	97.79	64.91	1238

Literature-anchored findings (GeneRIF, showing 40)

• Review. In some cases of CLL the malignant cells express both CD40 and CD154. Implications for autoimmunity and therapy are discussed. (PMID:11042507)
• The capacity of natural killer cells to induce B cell activation is dependent on the interaction of CD40 with its ligand CD154. (PMID:11714772)
• A CD40 molecule with mutated nonfunctional signaling domains acts as a dominant negative inhibitor and effectively prevents NF-kB activation and the induction of gene expression changes. (PMID:11714804)
• Ceramide-rich membrane rafts mediate CD40 clustering in b lymphocytes (PMID:11751974)
• CD40 ligation induces macrophage IL-10 and TNF-alpha production: differential use of the PI3K and p42/44 MAPK-pathways. (PMID:11792123)
• CD40:CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes. (PMID:11817328)
• CD40 and CD40L are important in autoimmunity and other immune processes. At least 5 signal transduction pathways are involved. (PMID:11826760)
• CD40 activation induces p53-dependent VEGF secretion and cell migration in multiple myeloma cells. (PMID:11830495)
• Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma -induced CD40 expression in microglia/macrophages. (PMID:11830590)
• Dissection of B cell differentiation during primary immune responses in transgenic mice expressing the human CD40 antigen (PMID:11867568)
• The selective triggering of CD40 on keratinocytes in vivo enhances cell-mediated immunity. (PMID:11870634)
• High constitutive expression of CD40 on salivary gland epithelial cells from Sjogren syndrome indicated their intrinsic activation. It was also expressed by lymphocytes, ductal epithelium and endothelium, but not other cells. (PMID:11876766)
• Short-circuiting long-lived humoral immunity by the heightened engagement of CD40. (PMID:11877469)
• Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia (PMID:11891278)
• Absence of CD40/CD40L interactions results in increased susceptibility to disseminated infection with C. albicans through decreased NO-dependent killing of Candida by macrophages. (PMID:11981834)
• clustering of CD40 ligand is required to form a functional contact with CD40 (PMID:12011072)
• IL-1 plays a prominent role in the inflammatory response initiated by CD40 ligation in intact human skin. (PMID:12039918)
• Studies of the mechanism of CD40-mediated apoptosis of human Burkitt lymphoma cell lines revealed an increase in bax messenger RNA with a subsequent increase in Bax protein in the mitochondria. (PMID:12070030)
• Endogenous Act1 is recruited to the CD40 receptor in human intestinal (HT29) and cervical (HeLa) epithelial cells upon stimulation with CD40 ligand, indicating that Act1 is involved in this signaling pathway. (PMID:12089335)
• plasmin induction of CD40 in human monocytes (PMID:12093796)
• mediates activation of NF-kappa B in airway epithelial cells (PMID:12122011)
• CD40 and CD80 molecules were observed to play a specific role in the induction of cytotoxic function but not in IFN-gamma production of IL-2-activated NK effectors. (PMID:12149421)
• Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells. (PMID:12165546)
• CD40-mediated p38 mitogen-activated protein kinase activation is required for immunoglobulin class switch recombination to IgE (PMID:12209089)
• CD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: implications for allergic inflammation (PMID:12209092)
• results suggest that in DG75 cells, TRAF3-induced MEK1 activation may be involved in CD40-mediated upregulation of IL-4-driven germline C epsilon transcription (PMID:12220533)
• Treatment of human gingival fibroblasts with human leukocyte elastase down-regulated CD40 expression & binding to CD40 ligand. CD40 reduction by direct proteolysis by HLE was seen in skin & lung fibroblasts (not monocytes, macrophages, & dendritic cells). (PMID:12223522)
• CD27 and CD40 co-stimulatory signals regulated the p53-amplified apoptotic pathway in B cells through the inhibition of p53-independent apoptotic pathway primarily induced by BCR ligation (PMID:12324477)
• CD40 induces human multiple myeloma cell migration via phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling. (PMID:12433678)
• CD40 is a surface receptor through which the activity of Btk can be stimulated in human B cells. (PMID:12437073)
• CD40 ligation on monocytes accelerates the maturation of dendritic cells in the presence of GM-CSF/IL-4 (PMID:12488500)
• Incubation of vascular endothelium with CD40L resulted in increased expression of cell adhesion molecules. Consequently, the adhesion of activated CD4+ T lymphocytes to CD40L treated endothelium was increased. (PMID:12507785)
• CD40 has pro- and anti-apoptotic functions in malignant B-cells and epithelial cancers [review] (PMID:12510151)
• CD40 is present in ovarian cancer cells and can be used for targeted gene delivery in a Coxsackie adenovirus receptor-independent. manner (PMID:12576427)
• Expression of this antigen may identify prognostically favorable subgroups of diffuse large B-cell lymphoma. (PMID:12576441)
• the CD40 gene was a new susceptibility gene for GD within certain families because it was both linked and associated with Graves disease (PMID:12593727)
• CD40 triggering enhances fludarabine-induced apoptosis of chronic lymphocytic leukemia B-cells through autocrine release of tumor necrosis factor-alpha and interferon-gama and tumor necrosis factor receptor-I-II upregulation. (PMID:12604404)
• Expression of CD40, CD54 and HLA-DR were seen in the hair structure including the dermal papilla in alopecia areata. (PMID:12624779)
• CD40L enhances the capacity of Mycobacterium tuberculosis-responsive CD8+ T cells to produce IFN-gamma by increasing the number of IFN-gamma-producing CD8+ T cells and the amount of IFN-gamma produced per cell. (PMID:12626576)
• endothelial CD40, through activation of the PI3K/Akt signaling pathway, regulates cell survival, proliferation, migration, and vessel-like structure formation, all steps considered critical for angiogenesis (PMID:12637493)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd40	ENSMUSG00000017652
rattus_norvegicus	Cd40	ENSRNOG00000018488

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 5 — P25942 (reviewed: P25942)

Alternative names: B-cell surface antigen CD40, Bp50, CD40L receptor, CDw40

All UniProt accessions (8): P25942, A0A087X1D0, A0A0S2Z349, A0A0S2Z3C7, A0A8Q3SI60, A0A8Q3WKP3, A0A8Q3WKP7, H0YE23

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion.

Subunit / interactions. Monomer and homodimer. The variant form found in the bladder carcinoma cell line Hu549 does not form homodimers. Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts with TRAF6 and MAP3K8; the interaction is required for ERK activation.

Subcellular location. Cell membrane Secreted.

Tissue specificity. B-cells and in primary carcinomas.

Disease relevance. Immunodeficiency with hyper-IgM 3 (HIGM3) [MIM:606843] A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P25942-1	I	yes
P25942-2	II

RefSeq proteins (7): NP_001241, NP_001289682, NP_001309350, NP_001309351, NP_001349687, NP_001411268, NP_690593 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR020435	TNFR_5	Family
IPR034021	TNFRSF5_N	Domain
IPR052135	TNFRSF5	Family

Pfam: PF00020

UniProt features (54 total): strand 21, disulfide bond 8, sequence variant 7, repeat 4, glycosylation site 2, topological domain 2, splice variant 2, helix 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
1LB6	X-RAY DIFFRACTION	1.8
1D00	X-RAY DIFFRACTION	2
7P3I	X-RAY DIFFRACTION	2.29
1CZZ	X-RAY DIFFRACTION	2.7
8YX1	X-RAY DIFFRACTION	2.7
5DMJ	X-RAY DIFFRACTION	2.79
8YX9	X-RAY DIFFRACTION	2.8
6PE8	X-RAY DIFFRACTION	2.84
6FAX	X-RAY DIFFRACTION	2.99
6PE9	X-RAY DIFFRACTION	3.13
5IHL	X-RAY DIFFRACTION	3.3
1FLL	X-RAY DIFFRACTION	3.5
3QD6	X-RAY DIFFRACTION	3.5
5DMI	X-RAY DIFFRACTION	3.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25942-F1	81.10	0.60

Antibody-complex structures (SAbDab): 8 — 5DMI, 5DMJ, 5IHL, 6FAX, 6PE8, 6PE9, 8YX1, 8YX9

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (8): 26–37, 38–51, 41–59, 62–77, 83–103, 105–119, 111–116, 125–143

Glycosylation sites (2): 153, 180

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

MSigDB gene sets: 527 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, CAR_TNFRSF25, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_B_CELL_ACTIVATION, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (43): immune response-regulating cell surface receptor signaling pathway (GO:0002768), intracellular calcium ion homeostasis (GO:0006874), inflammatory response (GO:0006954), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), B cell mediated immunity (GO:0019724), CD40 signaling pathway (GO:0023035), platelet activation (GO:0030168), positive regulation of B cell proliferation (GO:0030890), positive regulation of interleukin-12 production (GO:0032735), response to cobalamin (GO:0033590), response to type II interferon (GO:0034341), cellular response to erythropoietin (GO:0036018), B cell proliferation (GO:0042100), B cell activation (GO:0042113), defense response to protozoan (GO:0042832), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of angiogenesis (GO:0045766), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of isotype switching to IgG isotypes (GO:0048304), defense response to virus (GO:0051607), protein-containing complex assembly (GO:0065003), cellular response to lipopolysaccharide (GO:0071222), cellular response to mechanical stimulus (GO:0071260), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), positive regulation of protein kinase C signaling (GO:0090037), positive regulation of interleukin-4-mediated signaling pathway (GO:1902216), positive regulation of endothelial cell apoptotic process (GO:2000353), immune system process (GO:0002376), regulation of immunoglobulin production (GO:0002637), defense response (GO:0006952), response to bacterium (GO:0009617), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), response to nutrient levels (GO:0031667), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of immune response (GO:0050776)

GO Molecular Function (6): antigen binding (GO:0003823), enzyme binding (GO:0019899), protein domain specific binding (GO:0019904), ubiquitin protein ligase binding (GO:0031625), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), CD40 receptor complex (GO:0035631), neuronal cell body (GO:0043025), varicosity (GO:0043196), extracellular exosome (GO:0070062), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Adaptive Immune System	1
Cytokine Signaling in Immune system	1
TNFR2 non-canonical NF-kB pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell surface receptor signaling pathway	2
positive regulation of intracellular signal transduction	2
binding	2
protein binding	2
immune response-regulating signaling pathway	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
defense response	1
cell surface receptor signaling pathway via STAT	1
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
cell activation	1
blood coagulation	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
positive regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
response to vitamin	1
response to nitrogen compound	1
response to oxygen-containing compound	1
response to cytokine	1
innate immune response	1
response to erythropoietin	1
cellular response to cytokine stimulus	1
B cell activation	1
lymphocyte proliferation	1
lymphocyte activation	1
response to protozoan	1
defense response to other organism	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
intracellular signaling cassette	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1

Protein interactions and networks

STRING

3416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD40	CD80	P33681	999
CD40	CD40LG	P29965	999
CD40	CD28	P10747	997
CD40	TRAF6	Q9Y4K3	996
CD40	REL	Q04864	992
CD40	TRAF3	Q13114	992
CD40	RELA	Q04206	991
CD40	HSPA4	P34932	988
CD40	ICOS	Q9Y6W8	987
CD40	CD86	P42081	986
CD40	SELP	P16109	985
CD40	TNF	P01375	984
CD40	ICOSLG	O75144	977
CD40	CTLA4	P16410	973
CD40	TNFRSF13C	Q96RJ3	968

IntAct

105 interactions, top by confidence:

A	B	Type	Score
CD40	TRAF2	psi-mi:“MI:0915”(physical association)	0.960
TRAF2	CD40	psi-mi:“MI:0915”(physical association)	0.960
CD40	CMTM6	psi-mi:“MI:0915”(physical association)	0.670
CD40	SLC7A1	psi-mi:“MI:0915”(physical association)	0.670
TRAF6	CD40	psi-mi:“MI:0407”(direct interaction)	0.590
CYB561A3	CD40	psi-mi:“MI:0915”(physical association)	0.560
EBP	CD40	psi-mi:“MI:0915”(physical association)	0.560
MAL	CD40	psi-mi:“MI:0915”(physical association)	0.560
CD40	DEFB121	psi-mi:“MI:0915”(physical association)	0.560
CD40	SLC30A3	psi-mi:“MI:0915”(physical association)	0.560
CD40	MIP	psi-mi:“MI:0915”(physical association)	0.560
CD40	MFSD5	psi-mi:“MI:0915”(physical association)	0.560
CD40	TMEM147	psi-mi:“MI:0915”(physical association)	0.560
CD40	SLC39A13	psi-mi:“MI:0915”(physical association)	0.560
CD40	TLCD1	psi-mi:“MI:0915”(physical association)	0.560
CD40	CYB561A3	psi-mi:“MI:0915”(physical association)	0.560
CD40	INSIG2	psi-mi:“MI:0915”(physical association)	0.560
CD40	TMEM128	psi-mi:“MI:0915”(physical association)	0.560
CD40	PLP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (244): TRAF2 (Two-hybrid), FAF1 (Affinity Capture-Western), FAF1 (Reconstituted Complex), FAF1 (Two-hybrid), TRAF3 (Two-hybrid), CD40 (Affinity Capture-Western), TRAF1 (Affinity Capture-Western), CHUK (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), DIABLO (Affinity Capture-Western), CD40 (Affinity Capture-Western), IKBKB (Affinity Capture-Western), TRAF3 (Affinity Capture-Western), TRAF5 (Affinity Capture-Western), BIRC2 (Affinity Capture-Western)

ESM2 similar proteins: D4A6L0, E1BBQ2, O19131, P07174, P08138, P18519, P19438, P20959, P21744, P22692, P22934, P24591, P24854, P25118, P25942, P41272, P43489, P47741, P47879, P50555, P98174, Q05716, Q0VCT3, Q28203, Q3LRP1, Q3ZTK5, Q496Y0, Q4R4I0, Q5EAN7, Q5T848, Q5VV43, Q6UWJ8, Q7YRL5, Q8BX43, Q8C088, Q8C419, Q8HXH0, Q8K5A9, Q8SQ34, Q91VL8

Diamond homologs: A5D7R1, D3ZF92, O00300, O08712, O08727, O35305, O75509, O95407, P0DTN0, P20333, P25119, P25942, P25943, P27512, P29825, P36941, P43489, P83626, Q28203, Q3LRP1, Q3ZTK5, Q63199, Q7YRL5, Q8SQ34, Q9EPU5, Q9Y6Q6, O73559, P0DSV7, P0DSV8, P68636, P68637, P28908, P07174, P08138, P15725, P20334, P47741, P50284, Q07011, Q9Z0W1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CD40	“up-regulates activity”	TRAF2	binding
CD40LG	“up-regulates activity”	CD40	binding
CD40	up-regulates	Inflammation
CD40	“up-regulates activity”	TRAF3	binding
NfKb-p65/p50	“up-regulates quantity by expression”	CD40	“transcriptional regulation”
sirolimus	“down-regulates quantity by repression”	CD40
CD40	“up-regulates quantity by expression”	BCL2L1	“transcriptional regulation”
CD40	“up-regulates quantity by expression”	BIK	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of apoptotic process	6	12.2×	5e-04
positive regulation of canonical NF-kappaB signal transduction	5	8.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

297 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	6
Uncertain significance	82
Likely benign	149
Benign	25

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
17748	NM_001250.6(CD40):c.408A>T (p.Thr136=)	Pathogenic
17749	NM_001250.6(CD40):c.247T>C (p.Cys83Arg)	Pathogenic
17750	NM_001250.6(CD40):c.257-2A>T	Pathogenic
2024847	NM_001250.6(CD40):c.157G>T (p.Glu53Ter)	Pathogenic
2032027	NM_001250.6(CD40):c.33G>A (p.Trp11Ter)	Pathogenic
2424026	NC_000020.10:g.(?44746983)(44757679_?)del	Pathogenic
29611	NM_001250.6(CD40):c.95TAA[1] (p.Ile33del)	Pathogenic
3248233	NC_000020.10:g.(?44519965)(44751017_?)del	Pathogenic
3248346	NC_000020.10:g.(?44577592)(45362473_?)del	Pathogenic
3643241	NM_001250.6(CD40):c.87del (p.Lys29fs)	Pathogenic
3724127	NM_001250.6(CD40):c.287_297del (p.Thr96fs)	Pathogenic
4848600	NC_000020.10:g.(?44746952)(44758498_?)del	Pathogenic
631877	NM_001250.6(CD40):c.397C>T (p.Gln133Ter)	Pathogenic
2138351	NM_001250.6(CD40):c.832_*1del (p.Ter278AlaextTer?)	Likely pathogenic
2183112	NM_001250.6(CD40):c.1del (p.Met1fs)	Likely pathogenic
2777170	NM_001250.6(CD40):c.445G>A (p.Gly149Ser)	Likely pathogenic
2785002	NM_001250.6(CD40):c.646+1G>A	Likely pathogenic
2818861	NM_001250.6(CD40):c.497+1G>A	Likely pathogenic
3629833	NM_001250.6(CD40):c.430G>A (p.Glu144Lys)	Likely pathogenic

SpliceAI

1472 predictions. Top by Δscore:

Variant	Effect	Δscore
20:46118392:GCT:G	donor_gain	1.0000
20:46118395:G:GG	donor_gain	1.0000
20:46128222:TCA:T	donor_gain	1.0000
20:46128224:AGTGA:A	donor_loss	1.0000
20:46128225:G:C	donor_loss	1.0000
20:46128225:G:GG	donor_gain	1.0000
20:46128226:T:A	donor_loss	1.0000
20:46118390:CCGCT:C	donor_gain	0.9900
20:46118391:CGCT:C	donor_gain	0.9900
20:46118392:GCTG:G	donor_gain	0.9900
20:46118393:CT:C	donor_gain	0.9900
20:46122359:G:GG	donor_gain	0.9900
20:46122752:GATTG:G	donor_gain	0.9900
20:46122753:ATTGG:A	donor_loss	0.9900
20:46122754:TTGGT:T	donor_loss	0.9900
20:46122757:G:GA	donor_loss	0.9900
20:46122758:TAAGT:T	donor_loss	0.9900
20:46125871:TTCTA:T	donor_gain	0.9900
20:46126609:T:TA	acceptor_gain	0.9900
20:46126613:T:TA	acceptor_gain	0.9900
20:46126616:A:AG	acceptor_gain	0.9900
20:46126617:T:G	acceptor_gain	0.9900
20:46126625:C:G	acceptor_gain	0.9900
20:46126637:T:G	acceptor_gain	0.9900
20:46128136:A:AG	acceptor_gain	0.9900
20:46128137:G:GG	acceptor_gain	0.9900
20:46128220:TATCA:T	donor_gain	0.9900
20:46128223:CA:C	donor_gain	0.9900
20:46128227:GA:G	donor_loss	0.9900
20:46128328:A:AG	acceptor_gain	0.9900

AlphaMissense

1814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:46122301:T:C	F67L	0.996
20:46122303:C:A	F67L	0.996
20:46122303:C:G	F67L	0.996
20:46123173:T:C	F151L	0.990
20:46123175:C:A	F151L	0.990
20:46123175:C:G	F151L	0.990
20:46122331:T:A	C77S	0.985
20:46122332:G:C	C77S	0.985
20:46122302:T:G	F67C	0.984
20:46123203:T:A	C161S	0.984
20:46123204:G:C	C161S	0.984
20:46123214:G:C	W164C	0.982
20:46123214:G:T	W164C	0.982
20:46126698:T:A	C186S	0.982
20:46126699:G:C	C186S	0.982
20:46129011:A:C	S269R	0.980
20:46129013:T:A	S269R	0.980
20:46129013:T:G	S269R	0.980
20:46121889:T:A	C41S	0.979
20:46121890:G:C	C41S	0.979
20:46122660:T:A	C103S	0.978
20:46122661:G:C	C103S	0.978
20:46122349:T:A	C83S	0.977
20:46122350:G:C	C83S	0.977
20:46123174:T:G	F151C	0.976
20:46123203:T:C	C161R	0.976
20:46123158:T:A	C146S	0.975
20:46123159:G:C	C146S	0.975
20:46123176:T:C	S152P	0.975
20:46129007:A:C	K267N	0.975

dbSNP variants (sampled 300 via entrez): RS1000053915 (20:46120868 C>T), RS1000182570 (20:46123997 T>C), RS1000311280 (20:46116579 C>T), RS1000637688 (20:46123020 G>A,T), RS1001076318 (20:46128176 A>G), RS1001128452 (20:46127899 G>A,T), RS1001540702 (20:46116883 C>A,T), RS1001763118 (20:46124999 C>A), RS1001797227 (20:46124586 C>A,G), RS1001981055 (20:46116469 A>C), RS1002048694 (20:46117976 C>T), RS1002080352 (20:46123646 G>A), RS1002154035 (20:46123293 G>A,C), RS1002599530 (20:46118483 G>A), RS1002664736 (20:46119245 A>C,G)

Disease associations

OMIM: gene MIM:109535 | disease phenotypes: MIM:606843, MIM:256540, MIM:308230

GenCC curated gene-disease

Disease	Classification	Inheritance
hyper-IgM syndrome type 3	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hyper-IgM syndrome type 3	Definitive	AR

Mondo (3): hyper-IgM syndrome type 3 (MONDO:0011735), galactosialidosis (MONDO:0009737), hyper-IgM syndrome type 1 (MONDO:0010626)

Orphanet (3): Hyper-IgM syndrome type 3 (Orphanet:101090), Galactosialidosis (Orphanet:351), X-linked hyper-IgM syndrome (Orphanet:101088)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001875	Decreased total neutrophil count
HP:0002718	Recurrent bacterial infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002847	Impaired memory B cell generation
HP:0002849	Absence of lymph node germinal center
HP:0002959	Impaired Ig class switch recombination
HP:0003496	Increased circulating IgM level
HP:0004315	Decreased circulating IgG concentration
HP:0005479	Decreased circulating IgE concentration

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000232_3	Rheumatoid arthritis	8.000000e-09
GCST000425_6	Multiple sclerosis	1.000000e-07
GCST001198_64	Multiple sclerosis	5.000000e-10
GCST001341_6	Multiple sclerosis	5.000000e-06
GCST001455_3	Kawasaki disease	5.000000e-08
GCST001456_4	Kawasaki disease	6.000000e-09
GCST001725_65	Inflammatory bowel disease	1.000000e-13
GCST002318_1	Rheumatoid arthritis	4.000000e-18
GCST002318_64	Rheumatoid arthritis	1.000000e-16
GCST002879_4	Chronic hepatitis B infection	3.000000e-15
GCST003995_12	Tonsillectomy	7.000000e-12
GCST004131_122	Inflammatory bowel disease	2.000000e-06
GCST004132_43	Crohn’s disease	2.000000e-07
GCST005014_178	Tonsillectomy	7.000000e-12
GCST005531_69	Multiple sclerosis	8.000000e-16
GCST005537_55	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-12
GCST005568_22	Rheumatoid arthritis (ACPA-positive)	1.000000e-09
GCST005568_42	Rheumatoid arthritis (ACPA-positive)	9.000000e-11
GCST005569_16	Rheumatoid arthritis	2.000000e-07
GCST005752_163	Systemic lupus erythematosus	1.000000e-08
GCST006048_22	Rheumatoid arthritis (ACPA-positive)	2.000000e-13
GCST006959_141	Rheumatoid arthritis	3.000000e-14
GCST006959_51	Rheumatoid arthritis	4.000000e-14
GCST007062_6	Hodgkin’s lymphoma	2.000000e-08
GCST007400_68	Systemic lupus erythematosus	1.000000e-07
GCST009731_44	Blood protein levels in cardiovascular risk	2.000000e-121
GCST010979_6	Kawasaki disease	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0010607	tumor necrosis factor, receptor superfamily, member 5 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536411	Neuraminidase deficiency with beta-galactosidase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1250358 (SINGLE PROTEIN), CHEMBL4106122 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4810485	CD40		0.00	0
rs1883832	CD40		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Immune checkpoint catalytic receptors

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
mitazalimab	Agonist	11.0	pKd
iscalimab	Binding	9.16	pKd

ChEMBL bioactivities

11 potent at pChembl≥5 of 16 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL1241018
7.11	IC50	78	nM	CHEMBL1241017
6.77	IC50	170	nM	CHEMBL4080373
6.51	IC50	310	nM	CHEMBL4060985
6.44	IC50	360	nM	CHEMBL4090673
6.00	IC50	990	nM	CHEMBL4098397
5.65	IC50	2260	nM	CHEMBL4082979
5.63	IC50	2330	nM	CHEMBL4072368
5.35	IC50	4500	nM	CHEMBL4080373
5.03	IC50	9400	nM	CHEMBL4090673
5.00	IC50	9900	nM	CHEMBL1241019

PubChem BioAssay actives

11 with measured affinity, of 48 total; 9 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2,6-diamino-N-[2-[[(2S)-1-[[(2S)-1-[[6-[4-[(2S,5S,10S)-2,5-bis[4-[6-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2,6-diaminohexanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoylamino]butyl]-7,12-dioxo-1,4,8-triazacyclododec-10-yl]butylamino]-6-oxohexyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]hexanamide	512588: Inhibition of recombinant human CD40L:mouse CD8 tail binding to human CD40 by surface plasmon resonance method	ic50	0.0500	uM
(2S)-2,6-diamino-N-[2-[[(2S)-1-[[(2S)-1-[[6-[4-[(2S,5R,8S,11R,14S,17R)-8,14-bis[4-[6-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2,6-diaminohexanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoylamino]butyl]-5,11,17-trimethyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]butylamino]-6-oxohexyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]hexanamide	512588: Inhibition of recombinant human CD40L:mouse CD8 tail binding to human CD40 by surface plasmon resonance method	ic50	0.0780	uM
8-[[4-[4-[(4-methoxycarbonylbenzoyl)amino]phenyl]benzoyl]amino]naphthalene-1-sulfonic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	0.1700	uM
8-[[4-[4-[(4-nitrobenzoyl)amino]phenyl]benzoyl]amino]naphthalene-1-sulfonic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	0.3100	uM
4-[[4-[4-[(4-nitrobenzoyl)amino]phenyl]benzoyl]amino]naphthalene-1-carboxylic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	0.3600	uM
8-[[4-[4-(1H-benzotriazole-5-carbonylamino)phenyl]benzoyl]amino]naphthalene-1-sulfonic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	0.9900	uM
4-hydroxy-7-[[5-hydroxy-7-sulfo-6-[[2-sulfo-4-[(4-sulfophenyl)diazenyl]phenyl]diazenyl]naphthalen-2-yl]carbamoylamino]-3-[[2-sulfo-4-[(4-sulfophenyl)diazenyl]phenyl]diazenyl]naphthalene-2-sulfonic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	2.2600	uM
4-[[4-[4-[(4-nitrobenzoyl)amino]phenyl]benzoyl]amino]naphthalene-1-sulfonic acid	1465876: Inhibition of human Fc-conjugated CD40/FLAG-tagged biotinylated CD40L costimulatory protein-protein interaction incubated for 1 hr by ELISA-type assay	ic50	2.3300	uM
N’-[1,3-bis[3-[6-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2,6-diaminohexanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoylamino]propoxy]-2-[3-[6-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2,6-diaminohexanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoylamino]propoxymethyl]propan-2-yl]butanediamide	512588: Inhibition of recombinant human CD40L:mouse CD8 tail binding to human CD40 by surface plasmon resonance method	ic50	9.9000	uM

CTD chemical–gene interactions

136 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, increases expression, decreases reaction, decreases expression, affects response to substance	10
Valproic Acid	affects expression, increases expression	5
Arsenic	affects cotreatment, increases expression, decreases methylation, decreases expression, increases abundance	3
Poly I-C	affects cotreatment, increases secretion, increases expression	3
Tretinoin	increases expression, affects cotreatment, decreases expression	3
Particulate Matter	increases expression, increases reaction, affects expression, affects reaction	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
nickel sulfate	decreases reaction, increases expression	2
Ribomunyl	increases secretion, increases expression, affects cotreatment	2
mercuric bromide	decreases expression, affects cotreatment	2
lipopolysaccharide, E. coli O26-B6	increases expression	2
lipopolysaccharide, E coli O55-B5	increases expression	2
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	2
Gemcitabine	decreases expression	2
Curcumin	decreases expression, affects cotreatment, increases expression	2
Diethylhexyl Phthalate	increases expression, affects cotreatment, decreases expression	2
Dinitrochlorobenzene	increases expression	2
Fluorouracil	decreases response to substance, affects binding, affects cotreatment, decreases reaction	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases reaction, increases expression, affects binding, affects cotreatment	2
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression, affects expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	decreases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
TL8-506	affects cotreatment, increases expression	1
helenalin	decreases reaction, increases expression	1
2-anisidine	affects expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1250027	Binding	Inhibition of recombinant human CD40L:mouse CD8 tail binding to human CD40 by surface plasmon resonance method	C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L. — Nat Chem Biol

Cellosaurus cell lines

11 cell lines: 5 cancer cell line, 4 transformed cell line, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9832	293-CD40	Transformed cell line	Female
CVCL_A8CE	HEK-Blue CD40L	Transformed cell line	Female
CVCL_B0YY	Abcam U2OS CD40 KO	Cancer cell line	Female
CVCL_D7M3	Ubigene A-549 CD40 KO	Cancer cell line	Male
CVCL_D8IN	Ubigene HCT 116 CD40 KO	Cancer cell line	Male
CVCL_E6PL	Genomeditech CHO-K1 H_CD40(TNFRSF5)	Spontaneously immortalized cell line	Female
CVCL_E6TF	Genomeditech HEK-293 H_CD40(TNFRSF5) Reporter	Transformed cell line	Female
CVCL_E6VQ	Genomeditech Jurkat H_CD40(TNFRSF5) Reporter	Cancer cell line	Male
CVCL_KA33	CHO-K1/CD40	Spontaneously immortalized cell line	Female
CVCL_UE25	293T human CD40	Transformed cell line	Female

Clinical trials (associated diseases)

7 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01416467	Not specified	COMPLETED	Characterization of the Patient Population With Galactosialidosis
NCT01891422	Not specified	COMPLETED	Longitudinal Studies of the Glycoproteinoses
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT00004341	Not specified	UNKNOWN	Study of Genetic and Molecular Defects in Primary Immunodeficiency Disorders
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies