CD40LG

Summary

CD40LG (CD40 ligand, HGNC:11935) is a protein-coding gene on chromosome Xq26.3, encoding CD40 ligand (P29965). Cytokine that acts as a ligand to CD40/TNFRSF5. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 959 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyper-IgM syndrome type 1 (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 347 total — 78 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11935
Approved symbol	CD40LG
Name	CD40 ligand
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	CD40L, TRAP, gp39, hCD40L, CD154, CD40-L, HIGM1, T-BAM
Ensembl gene	ENSG00000102245
Ensembl biotype	protein_coding
OMIM	300386
Entrez	959

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000370628, ENST00000370629, ENST00000695724, ENST00000695725, ENST00000695726, ENST00000695727, ENST00000695728, ENST00000695729

RefSeq mRNA: 1 — MANE Select: NM_000074 NM_000074

CCDS: CCDS14659

Canonical transcript exons

ENST00000370629 — 5 exons

Exon	Start	End
ENSE00000677016	136650266	136650397
ENSE00000677017	136654373	136654430
ENSE00000677018	136656356	136656418
ENSE00001125156	136659039	136660390
ENSE00001453187	136648158	136648404

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 87.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.0913 / max 815.4538, expressed in 150 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197721	4.1941	142
197722	0.8972	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	87.82	gold quality
lymph node	UBERON:0000029	78.93	gold quality
blood	UBERON:0000178	76.57	gold quality
vermiform appendix	UBERON:0001154	74.90	gold quality
rectum	UBERON:0001052	70.28	gold quality
caecum	UBERON:0001153	69.10	gold quality
spleen	UBERON:0002106	68.19	gold quality
ileal mucosa	UBERON:0000331	68.09	silver quality
gall bladder	UBERON:0002110	68.03	gold quality
cervix squamous epithelium	UBERON:0006922	67.79	gold quality
mucosa of transverse colon	UBERON:0004991	67.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.66	gold quality
small intestine	UBERON:0002108	63.88	gold quality
leukocyte	CL:0000738	62.72	gold quality
bone marrow	UBERON:0002371	62.53	gold quality
colonic epithelium	UBERON:0000397	62.12	silver quality
duodenum	UBERON:0002114	61.46	gold quality
endothelial cell	CL:0000115	60.88	gold quality
bone marrow cell	CL:0002092	60.86	silver quality
mononuclear cell	CL:0000842	60.08	gold quality
tonsil	UBERON:0002372	59.92	gold quality
monocyte	CL:0000576	59.83	gold quality
upper lobe of left lung	UBERON:0008952	58.90	gold quality
right coronary artery	UBERON:0001625	58.36	gold quality
smooth muscle tissue	UBERON:0001135	57.83	gold quality
omental fat pad	UBERON:0010414	57.55	gold quality
peritoneum	UBERON:0002358	57.51	gold quality
upper lobe of lung	UBERON:0008948	57.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.69	gold quality
right lung	UBERON:0002167	56.59	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	58.04
E-CURD-46	yes	36.56
E-HCAD-1	yes	35.74
E-MTAB-8410	yes	15.88
E-ANND-3	yes	5.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IGSF6	Repression

Upstream regulators (CollecTRI, top): AKNA, AP1, EGR1, EGR3, FOS, GATA3, JUN, JUND, MITF, NFAM1, NFATC2, NFATC3, NFIL3, NFKB1, NFKB, NR3C1, REL, RELA, STAT1, TFE3, TFEB, USF1, USF2

miRNA regulators (miRDB)

73 targeting CD40LG, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-377-5P	99.70	65.28	712

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

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 regulated by the interaction of CD40 with its ligand CD154. (PMID:11714772)
• the CD40L gene 3’-flanking region acts as a T cell-specific classical transcriptional enhancer by a NF-kappaB p50-dependent mechanism. (PMID:11751888)
• CD40/CD40L interactions are important for the activation of macrophages as effector cells that mediate inflammation and tissue damage in T cell-mediated inflammatory processes. (PMID:11792121)
• CD40 ligand contacts between fibroblasts and cells secreting IL-4 may promote the profibrotic effects of IL-4 by affecting signal transduction and reducing the anti-fibrotic effects of IFN-gamma. (PMID:11801648)
• CD40L-deficient T cells in carriers of X-linked hyper-IgM syndrome are minimally impaired in comparison with CD40L-expressing T cells in several parameters of T cell priming. (PMID:11801691)
• sCD40L levels in blood, quantities released from platelets ex vivo, and quantities released from SFFLRN stimulated platelets ex vivo were compared for preeclamptic and normal pregnancies. (PMID:11816717)
• 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)
• review of the role of CD154 and the type-1 cytokine response (PMID:11865444)
• CD40L appears to be an alphaIIbbeta3 integrin ligand, a platelet agonist, and necessary for stability of arterial thrombi. (PMID:11875495)
• Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia (PMID:11891278)
• Role of surface IgM and IgD on survival/apoptosis of B-cell chronic lymphocytic leukemia cells. (PMID:11902141)
• Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells. (PMID:11902332)
• dinucleotide microsatellite in multiple sclerosis (PMID:11918631)
• Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome. (PMID:11922919)
• Burkitt lymphoma cell population depletion activates autonomous CD154-dependent survival. (PMID:11964311)
• role in inducing tissue factor expression in endothelial cells (PMID:11978801)
• Levels of soluble CD40 ligand (CD154) in serum are increased in human immunodeficiency virus type 1-infected patients and correlate with CD4(+) T-cell counts (PMID:11986259)
• Clustering of CD40 ligand is required to form a functional contact with CD40 (PMID:12011072)
• cd154 (cd40 ligand)is expressed during treatment with calcineurin inhibitors after organ transplantation. (PMID:12042657)
• Leishmania priming of human dendritic cells for CD40 ligand-induced interleukin-12p70 secretion is strain and species dependent (PMID:12117904)
• CD40 ligand (CD154) does not contribute to lymphocyte-mediated inhibition of virulent Mycobacterium tuberculosis within human monocytes (PMID:12117990)
• association of a common variant in CD40L with a malaria resistance phenotype (PMID:12140747)
• effect of platelet-derived CD40L on the tissue factor activity of human CD40-positive melanoma cells and monocytes (PMID:12192302)
• In human lung myofibroblasts,CD40 ligand is induced by lipopolysaccharide, thrombin and TNF-alpha. (PMID:12207328)
• CD154 expression in renal cell carcinoma (PMID:12209602)
• Treatment of human gingival fibroblasts with human leukocyte elastase down-regulated CD40 binding to CD40 ligand. HLE treatment of HGF decreases IL-8 and macrophage chemoattractant protein-1 production by HGF when stimulated by CD40L. (PMID:12223522)
• Impact of both donor and recipient strains on cardiac allograft survival after blockade of the cd40 costimulatory pathway (PMID:12352896)
• upregulation of CD40L on platelets triggers CD40L-dependent matrix degradation by vascular endothelial cells (PMID:12379582)
• CD40L induces proliferation, self-renewal, rescue from apoptosis, and production of cytokines by CD40-expressing AML blasts. (PMID:12423681)
• CD40L has a role in activating antigen-presenting cells (APCs) and thereby initiating the human immune response in HIV infection (PMID:12427285)
• findings suggests that there are two groups of immune thrombocytopenic purpura (ITP) patients, one with elevated and one with normal of sCD40L; pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway (PMID:12460235)
• CD154 function is determined by binding to PTB and PTB-T and is involved in autoimmune disease (PMID:12509450)
• CD40L expression on CD4+ T-cells is significantly higher in patients with Kawasaki disease (KD) than in the febrile control group, which implies that CD40L over-expression might play a role in the immunopathogenesis of KD. (PMID:12563087)
• CD40L can induce maturation of monocyte-derived dendritic cells and elicit sustained antiviral cytotoxic T lymphocyte responses, either alone or cooperatively with TNF-alpha or RANKL. (PMID:12574344)
• Proapoptotic genes BAX and CD40L are predictors of survival in transitional cell carcinoma of the bladder. (PMID:12592374)
• Serum levels of sCD40L significantly higher in MCTD than in healthy individuals. May play role in pathogenesis of MCTD. (PMID:12605316)
• A key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. (PMID:12672403)
• high shear stress induces CD40L translocation to the platelet surface, which is mediated by the von Willebrand factor (VWF)-GP Ibalpha interaction and enhanced in the presence of a low concentration of epinephrine (PMID:12676191)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd40lg	ENSMUSG00000031132
rattus_norvegicus	Cd40lg	ENSRNOG00000000871

Paralogs (8): FASLG (ENSG00000117560), TNFSF11 (ENSG00000120659), TNFSF10 (ENSG00000121858), TNFSF14 (ENSG00000125735), TNFSF15 (ENSG00000181634), LTA (ENSG00000226979), LTB (ENSG00000227507), TNF (ENSG00000232810)

Protein

Protein identifiers

CD40 ligand — P29965 (reviewed: P29965)

Alternative names: T-cell antigen Gp39, TNF-related activation protein, Tumor necrosis factor ligand superfamily member 5

All UniProt accessions (4): P29965, A0A8Q3WKP2, A0A8Q3WL88, Q3L8U2

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that acts as a ligand to CD40/TNFRSF5. Costimulates T-cell proliferation and cytokine production. Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation. Induces the activation of NF-kappa-B. Induces the activation of kinases MAPK8 and PAK2 in T-cells. Induces tyrosine phosphorylation of isoform 3 of CD28. Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4. Involved in immunoglobulin class switching. Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling.

Subunit / interactions. Homotrimer. Interacts with isoform 3 of CD28. CD40 ligand, soluble form: Exists as either a monomer or a homotrimer. Forms a ternary complex between CD40 and integrins for CD40-CD40LG signaling.

Subcellular location. Cell membrane. Cell surface Secreted.

Tissue specificity. Specifically expressed on activated CD4+ T-lymphocytes.

Post-translational modifications. The soluble form derives from the membrane form by proteolytic processing. N-linked glycan is a mixture of high mannose and complex type. Glycan structure does not influence binding affinity to CD40. Not O-glycosylated.

Disease relevance. Immunodeficiency with hyper-IgM, type 1 (HIGM1) [MIM:308230] 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tumor necrosis factor family.

RefSeq proteins (1): NP_000065* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003263	CD40L	Family
IPR006052	TNF_dom	Domain
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR021184	TNF_CS	Conserved_site

Pfam: PF00229

UniProt features (64 total): sequence variant 35, strand 12, mutagenesis site 4, chain 2, topological domain 2, turn 2, glycosylation site 2, transmembrane region 1, domain 1, site 1, helix 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6W9G	X-RAY DIFFRACTION	1.82
1ALY	X-RAY DIFFRACTION	2
7SGM	X-RAY DIFFRACTION	2
3LKJ	X-RAY DIFFRACTION	2.5
6BRB	X-RAY DIFFRACTION	2.82
1I9R	X-RAY DIFFRACTION	3.1
9I5N	ELECTRON MICROSCOPY	3.4
3QD6	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29965-F1	82.34	0.55

Antibody-complex structures (SAbDab): 1 — 1I9R

Functional residue map

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

Catalytic / active sites (1): 112–113 (cleavage)

Disulfide bonds (1): 178–218

Glycosylation sites (2): 240, 240

Mutagenesis-validated functional residues (4):

Position	Phenotype
170	decreases itga5:itgb1 binding, b-cell activation, activation of nf-kappa-b signaling, and anti-apoptotic signaling; in s
224	decreases itga5:itgb1 binding, b-cell activation, activation of nf-kappa-b signaling, and anti-apoptotic signaling; when
226	decreases itga5:itgb1 binding, b-cell activation, activation of nf-kappa-b signaling, and anti-apoptotic signaling; when
252	decreases itga5:itgb1 binding, b-cell activation, activation of nf-kappa-b signaling, and anti-apoptotic signaling; in s

Function

Pathways and Gene Ontology

Reactome pathways

6 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
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 413 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_B_CELL_ACTIVATION, GCANCTGNY_MYOD_Q6, GOBP_PLATELET_ACTIVATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_LYMPHOCYTE_COSTIMULATION, GOCC_CELL_SURFACE, GOBP_B_CELL_PROLIFERATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (26): regulation of immunoglobulin production (GO:0002637), inflammatory response (GO:0006954), leukocyte cell-cell adhesion (GO:0007159), cell surface receptor signaling pathway (GO:0007166), integrin-mediated signaling pathway (GO:0007229), CD40 signaling pathway (GO:0023035), platelet activation (GO:0030168), B cell differentiation (GO:0030183), T cell costimulation (GO:0031295), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-4 production (GO:0032753), B cell proliferation (GO:0042100), positive regulation of T cell proliferation (GO:0042102), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), isotype switching (GO:0045190), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of endothelial cell apoptotic process (GO:2000353), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), regulation of immune system process (GO:0002682), immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165), regulation of gene expression (GO:0010468), signaling (GO:0023052)

GO Molecular Function (7): cytokine activity (GO:0005125), tumor necrosis factor receptor binding (GO:0005164), CD40 receptor binding (GO:0005174), integrin binding (GO:0005178), protein serine/threonine kinase activator activity (GO:0043539), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Immune System	2
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
positive regulation of cytokine production	3
cellular anatomical structure	3
cell surface receptor signaling pathway	2
B cell activation	2
positive regulation of T cell activation	2
tumor necrosis factor receptor superfamily binding	2
immunoglobulin production	1
regulation of production of molecular mediator of immune response	1
defense response	1
cell-cell adhesion	1
signal transduction	1
cell activation	1
blood coagulation	1
lymphocyte differentiation	1
lymphocyte costimulation	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
lymphocyte proliferation	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
positive regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
extrinsic apoptotic signaling pathway	1
positive regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
receptor ligand activity	1

Protein interactions and networks

STRING

3058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD40LG	CD40	P25942	999
CD40LG	CD80	P33681	998
CD40LG	CD86	P42081	998
CD40LG	CD28	P10747	997
CD40LG	ICOS	Q9Y6W8	990
CD40LG	ICOSLG	O75144	989
CD40LG	A0A087X1L8	A0A087X1L8	988
CD40LG	SELPLG	Q14242	982
CD40LG	CD4	P01730	976
CD40LG	CD70	P32970	964
CD40LG	TNFSF4	P23510	958
CD40LG	SELP	P16109	944
CD40LG	TNFRSF13B	O14836	937
CD40LG	TNFRSF4	P43489	936
CD40LG	CD276	Q5ZPR3	935

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CD40LG	CD40	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (12): CD40LG (Affinity Capture-RNA), HPR (Affinity Capture-Western), APOA1 (Affinity Capture-Western), RNF128 (Affinity Capture-Western), CD40LG (Biochemical Activity), PHB (Reconstituted Complex), CD40LG (Affinity Capture-MS), CD40 (Affinity Capture-Western), TRAF2 (Affinity Capture-Western), BIRC2 (Affinity Capture-Western), BIRC3 (Affinity Capture-Western), TRAF1 (Affinity Capture-Western)

ESM2 similar proteins: D5K8A9, O02757, O02765, O35734, O97605, O97626, P04924, P06804, P16599, P23563, P27548, P29965, P31042, P35330, P36939, P36940, P41047, P43303, P43488, P48023, P51749, P59694, P63304, P63305, P63306, P63307, P63308, Q28071, Q539C2, Q5NKV2, Q5U462, Q75N23, Q7TS55, Q861W5, Q8BHK6, Q8IYV9, Q95MQ5, Q9BDM3, Q9BDM7, Q9BDN1

Diamond homologs: O97605, O97626, P27548, P29965, P51749, P63304, P63305, Q95MQ5, Q9BDM3, Q9BDM7, Q9BDN3, Q9I8D8, Q9Z2V2, P59694, Q75N23, O35734, O77510, O77764, P01374, P01375, P04924, P06804, P09225, P10154, P13296, P16599, P19101, P23383, P23563, P26445, P29553, P33620, P36939, P36940, P41047, P48094, P51435, P51742, P51743, P59684

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CD40LG	down-regulates	PTPN7
CD40LG	“up-regulates activity”	CD40	binding
CD40LG	“down-regulates quantity by repression”	IGSF6	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	78
Likely pathogenic	31
Uncertain significance	79
Likely benign	84
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070422	NM_000074.3(CD40LG):c.470del (p.Asn157fs)	Pathogenic
1071618	NM_000074.3(CD40LG):c.15C>A (p.Tyr5Ter)	Pathogenic
1074317	NM_000074.3(CD40LG):c.346+1G>A	Pathogenic
11157	NM_000074.3(CD40LG):c.703G>C (p.Ala235Pro)	Pathogenic
11159	NM_000074.3(CD40LG):c.680G>T (p.Gly227Val)	Pathogenic
11160	NM_000074.3(CD40LG):c.464T>C (p.Leu155Pro)	Pathogenic
11161	CD40LG, THR211ASP	Pathogenic
11163	NM_000074.3(CD40LG):c.419G>A (p.Trp140Ter)	Pathogenic
11166	NM_000074.3(CD40LG):c.412_419del	Pathogenic
11167	CD40LG, 10-BP DEL	Pathogenic
11168	NM_000074.3(CD40LG):c.368C>A (p.Ala123Glu)	Pathogenic
11169	NM_000074.3(CD40LG):c.189dup (p.Val64fs)	Pathogenic
11170	NG_007280.1:g.5145_5146insAluAluYb8inv	Pathogenic
1195319	NM_000074.3(CD40LG):c.289-2A>C	Pathogenic
1327990	NM_000074.3(CD40LG):c.166G>T (p.Glu56Ter)	Pathogenic
1381599	NM_000074.3(CD40LG):c.156+2T>C	Pathogenic
1402799	NM_000074.3(CD40LG):c.409+1G>C	Pathogenic
1405864	NM_000074.3(CD40LG):c.385G>T (p.Glu129Ter)	Pathogenic
1413373	NM_000074.3(CD40LG):c.598A>T (p.Arg200Ter)	Pathogenic
1423116	NM_000074.3(CD40LG):c.289-1G>A	Pathogenic
1444168	NM_000074.3(CD40LG):c.478C>T (p.Gln160Ter)	Pathogenic
1454482	NC_000023.10:g.(?135730388)(135737600_?)del	Pathogenic
1706555	NM_000074.3(CD40LG):c.161_162insG (p.Asp55fs)	Pathogenic
1803793	NM_000074.3(CD40LG):c.229del (p.Arg77fs)	Pathogenic
1996844	NM_000074.3(CD40LG):c.43del (p.Thr15fs)	Pathogenic
1997026	NM_000074.3(CD40LG):c.268C>T (p.Gln90Ter)	Pathogenic
2013065	NM_000074.3(CD40LG):c.431del (p.Gly144fs)	Pathogenic
2039120	NM_000074.3(CD40LG):c.299T>A (p.Leu100Ter)	Pathogenic
2054209	NM_000074.3(CD40LG):c.756del (p.Phe253fs)	Pathogenic
2092047	NM_000074.3(CD40LG):c.340del (p.Gln114fs)	Pathogenic

SpliceAI

389 predictions. Top by Δscore:

Variant	Effect	Δscore
X:136650259:A:AG	acceptor_gain	1.0000
X:136650260:A:G	acceptor_gain	1.0000
X:136650264:A:AG	acceptor_gain	1.0000
X:136650264:A:G	acceptor_loss	1.0000
X:136650265:G:GG	acceptor_gain	1.0000
X:136650265:GATA:G	acceptor_gain	1.0000
X:136650398:G:GC	donor_loss	1.0000
X:136656350:TTTCA:T	acceptor_loss	1.0000
X:136656351:TTCA:T	acceptor_loss	1.0000
X:136656353:CA:C	acceptor_loss	1.0000
X:136656355:G:GC	acceptor_loss	1.0000
X:136648400:ACAAG:A	donor_loss	0.9900
X:136648402:AAGGT:A	donor_loss	0.9900
X:136648403:AGG:A	donor_loss	0.9900
X:136648405:GTA:G	donor_loss	0.9900
X:136648406:T:G	donor_loss	0.9900
X:136656354:A:AG	acceptor_gain	0.9900
X:136656355:G:GG	acceptor_gain	0.9900
X:136659037:A:AG	acceptor_gain	0.9900
X:136659038:G:GA	acceptor_gain	0.9900
X:136659038:GT:G	acceptor_gain	0.9900
X:136650398:G:GG	donor_gain	0.9800
X:136656354:AGGT:A	acceptor_gain	0.9800
X:136656355:GGT:G	acceptor_gain	0.9800
X:136656355:GGTG:G	acceptor_gain	0.9800
X:136656417:TGGTA:T	donor_loss	0.9800
X:136656419:G:GG	donor_gain	0.9800
X:136656419:G:T	donor_loss	0.9800
X:136656420:TAA:T	donor_loss	0.9800
X:136656421:AA:A	donor_loss	0.9800

AlphaMissense

1733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:136659047:T:A	W140R	0.996
X:136659047:T:C	W140R	0.996
X:136659049:G:C	W140C	0.996
X:136659049:G:T	W140C	0.996
X:136659345:T:A	V239D	0.989
X:136659399:G:A	G257D	0.987
X:136659158:T:C	F177L	0.985
X:136659160:C:A	F177L	0.985
X:136659160:C:G	F177L	0.985
X:136656391:A:C	S128R	0.983
X:136656393:T:A	S128R	0.983
X:136656393:T:G	S128R	0.983
X:136650323:T:A	C72S	0.982
X:136650324:G:C	C72S	0.982
X:136659048:G:C	W140S	0.981
X:136659321:T:C	L231S	0.981
X:136659314:T:C	F229L	0.979
X:136659316:T:A	F229L	0.979
X:136659316:T:G	F229L	0.979
X:136659111:T:C	L161P	0.978
X:136659134:T:G	Y169D	0.977
X:136659398:G:C	G257R	0.976
X:136659153:T:A	V175D	0.975
X:136659246:T:C	L206P	0.975
X:136659117:T:A	V163D	0.973
X:136659405:T:C	L259P	0.972
X:136650323:T:C	C72R	0.971
X:136659390:C:A	T254K	0.971
X:136659392:T:C	S255P	0.971
X:136648385:T:C	L46P	0.970

dbSNP variants (sampled 300 via entrez): RS1000546748 (X:136650966 G>A), RS1000550722 (X:136660169 G>A), RS1000866634 (X:136656066 G>A), RS1001276404 (X:136655647 T>C), RS1001615881 (X:136650801 C>T), RS1001714115 (X:136657498 G>A), RS1001915392 (X:136659381 C>A), RS1002714772 (X:136652963 C>A,T), RS1003195609 (X:136655350 T>C), RS1003733851 (X:136652836 G>A), RS1003957406 (X:136657094 C>T), RS1004051141 (X:136654374 A>G), RS1004520254 (X:136647193 A>G), RS1004611925 (X:136646678 G>T), RS1004627667 (X:136656964 C>A,G,T)

Disease associations

OMIM: gene MIM:300386 | disease phenotypes: MIM:308230, MIM:607594

GenCC curated gene-disease

Disease	Classification	Inheritance
hyper-IgM syndrome type 1	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hyper-IgM syndrome type 1	Definitive	XL

Mondo (3): hyper-IgM syndrome type 1 (MONDO:0010626), common variable immunodeficiency (MONDO:0015517), hyper-IgM syndrome (MONDO:0003947)

Orphanet (2): X-linked hyper-IgM syndrome (Orphanet:101088), OBSOLETE: Common variable immunodeficiency (Orphanet:1572)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000155	Oral ulcer
HP:0000230	Gingivitis
HP:0001263	Global developmental delay
HP:0001287	Meningitis
HP:0001347	Hyperreflexia
HP:0001394	Cirrhosis
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001878	Hemolytic anemia
HP:0002014	Diarrhea
HP:0002240	Hepatomegaly
HP:0002376	Developmental regression
HP:0002718	Recurrent bacterial infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002783	Recurrent lower respiratory tract infections
HP:0002847	Impaired memory B cell generation
HP:0002849	Absence of lymph node germinal center
HP:0002959	Impaired Ig class switch recombination
HP:0002961	Dysgammaglobulinemia
HP:0003261	Increased circulating IgA concentration
HP:0003496	Increased circulating IgM level
HP:0003593	Infantile onset
HP:0004315	Decreased circulating IgG concentration
HP:0005419	Decreased T cell activation
HP:0005479	Decreased circulating IgE concentration
HP:0009098	Chronic oral candidiasis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003097_45	Pediatric autoimmune diseases	1.000000e-08
GCST009565_1	CD40 ligand levels	1.000000e-25
GCST90002388_278	Lymphocyte count	1.000000e-11
GCST90002400_6	Plateletcrit	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004790	CD40 ligand measurement
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017074	Common Variable Immunodeficiency	C20.673.330
D053306	Hyper-IgM Immunodeficiency Syndrome	C15.378.147.333.249; C16.320.413; C16.320.798.625; C20.673.430.250; C20.673.795.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3580491 (SINGLE PROTEIN), CHEMBL4106121 (PROTEIN-PROTEIN INTERACTION), CHEMBL4106122 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1126535	CD40LG		0.00	0

ChEMBL bioactivities

8 potent at pChembl≥5 of 13 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
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

PubChem BioAssay actives

8 with measured affinity, of 46 total; 6 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
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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases reaction, increases expression, affects activity, increases reaction (+1 more)	3
Atorvastatin	decreases expression	2
Air Pollutants	affects expression	2
Aspirin	decreases expression	2
Doxorubicin	decreases response to substance, affects cotreatment, increases expression, decreases reaction, increases cleavage (+1 more)	2
Erythrosine	affects binding, decreases reaction	2
Paclitaxel	decreases reaction, increases cleavage, increases reaction, decreases response to substance, affects cotreatment (+1 more)	2
Reactive Oxygen Species	affects cotreatment, decreases reaction, increases abundance, affects binding, increases reaction (+4 more)	2
Particulate Matter	affects expression, decreases methylation, increases expression	2
bisphenol F	decreases expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
diphenyleneiodonium	affects binding, affects cotreatment, decreases reaction, increases abundance	1
emulphogene BC 720	increases expression	1
gallein	decreases reaction, affects binding	1
3,3’-diindolylmethane	increases expression	1
sodium arsenite	decreases expression	1
indirubin	affects cotreatment, decreases reaction, increases expression	1
diphenyliodonium	affects cotreatment, decreases reaction, increases abundance, increases reaction, increases expression (+1 more)	1
candesartan	decreases expression, increases reaction	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, increases reaction, affects cotreatment, decreases reaction	1
bisphenol S	increases expression	1
Aspirin, Dipyridamole Drug Combination	decreases expression	1
Fingolimod Hydrochloride	decreases expression	1
Clopidogrel	decreases reaction, increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Vemurafenib	increases expression, affects cotreatment	1
Eptifibatide	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4688318	Binding	Inhibition of CD40L (unknown origin)	Biologic-like In Vivo Efficacy with Small Molecule Inhibitors of TNFα Identified Using Scaffold Hopping and Structure-Based Drug Design Approaches. — J Med Chem

Cellosaurus cell lines

14 cell lines: 10 transformed cell line, 2 cancer cell line, 1 telomerase immortalized cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2Z02	ID00002	Transformed cell line	Male
CVCL_2Z27	ID00063	Transformed cell line	Male
CVCL_2Z28	ID00064	Transformed cell line	Male
CVCL_4V25	293-CD40L	Transformed cell line	Female
CVCL_4V26	293-CD40L-sCD40L	Transformed cell line	Female
CVCL_A2XK	YK6-CD40Lg-IL21	Telomerase immortalized cell line	Male
CVCL_B8D3	Abcam HCT 116 CD40LG KO	Cancer cell line	Male
CVCL_B9FA	Abcam A-549 CD40LG KO	Cancer cell line	Male
CVCL_E3RF	HS5-CD40L	Transformed cell line	Male
CVCL_E3RI	HS5-CD40L-IL4	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT01489618	PHASE2	TERMINATED	Prime Boost Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02579967	PHASE2	RECRUITING	Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
NCT03663933	PHASE2	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation
NCT04339777	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
NCT04925375	PHASE2	RECRUITING	Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
NCT05593588	PHASE2	ENROLLING_BY_INVITATION	Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency
NCT06897358	PHASE2	ACTIVE_NOT_RECRUITING	Leniolisib for Immune Dysregulation in CVID
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
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
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00004695	Not specified	COMPLETED	Randomized Study of Polyethylene-Glycol-Conjugated Interleukin 2 in Patients With Common Variable Immunodeficiency
NCT00015431	Not specified	COMPLETED	Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin
NCT00943514	Not specified	RECRUITING	Natural History of Bronchiectasis
NCT01196702	Not specified	COMPLETED	Lymphocyte Immunophenotyping in Common Variable Immunodeficiency
NCT01981785	Not specified	UNKNOWN	Investigation of Immune Disorders and Deficiencies
NCT02960399	Not specified	TERMINATED	Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
NCT03188419	Not specified	COMPLETED	Breadth of Donor Options for People With Inherited Diseases Requiring Allogeneic Hematopoietic Stem Cell Transplant in the Era of Alternative Donor Transplants Using Post-Transplantation Cyclophosphamide
NCT03211689	Not specified	COMPLETED	The Impact of Exercise on Stress, Fatigue, and Quality of Life in Individuals With Primary Immunodeficiency Disease
NCT03534479	Not specified	COMPLETED	Human IgGs and Endothelial Function in Vivo in Humans
NCT05310604	Not specified	COMPLETED	Early Detection of Primary Antibody Deficiencies in Primary Care Facilities by an Algorithm Driven Selection of Serologic Testing in Individuals at Risk.
NCT05321407	Not specified	ACTIVE_NOT_RECRUITING	COVID-19 Vaccine Responses in PIDD Subjects