MYD88

Summary

MYD88 (MYD88 innate immune signal transduction adaptor, HGNC:7562) is a protein-coding gene on chromosome 3p22.2, encoding Myeloid differentiation primary response protein MyD88 (Q99836). Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. In precision oncology, MYD88 L265P confers sensitivity to Ibrutinib in Lymphoplasmacytic Lymphoma (CIViC Level B); 2 further curated variant–drug associations are listed below.

This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 4615 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pyogenic bacterial infections due to MyD88 deficiency (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 192 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• MANE Select transcript: NM_002468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7562
Approved symbol	MYD88
Name	MYD88 innate immune signal transduction adaptor
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172936
Ensembl biotype	protein_coding
OMIM	602170
Entrez	4615

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000416282, ENST00000417037, ENST00000421516, ENST00000460295, ENST00000463956, ENST00000481122, ENST00000484513, ENST00000650112, ENST00000650905, ENST00000651800, ENST00000652213, ENST00000652590, ENST00000699084, ENST00000699085, ENST00000699086, ENST00000862995, ENST00000969067, ENST00000969068, ENST00000969069, ENST00000969070

RefSeq mRNA: 8 — MANE Select: NM_002468 NM_001172566, NM_001172567, NM_001172568, NM_001172569, NM_001365876, NM_001365877, NM_001374787, NM_002468

CCDS: CCDS2674, CCDS54565, CCDS54566, CCDS54567, CCDS54568, CCDS93244

Canonical transcript exons

ENST00000650905 — 5 exons

Exon	Start	End
ENSE00003478577	38140388	38140568
ENSE00003552693	38140757	38140848
ENSE00003582265	38139864	38139998
ENSE00003899079	38141132	38143022
ENSE00003899467	38138661	38139028

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.1142 / max 468.5162, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36093	39.1060	1806
36094	0.0082	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	98.24	gold quality
mononuclear cell	CL:0000842	98.23	gold quality
monocyte	CL:0000576	98.22	gold quality
granulocyte	CL:0000094	98.13	gold quality
blood	UBERON:0000178	98.03	gold quality
gingival epithelium	UBERON:0001949	97.48	gold quality
gingiva	UBERON:0001828	96.97	gold quality
ileal mucosa	UBERON:0000331	96.94	gold quality
periodontal ligament	UBERON:0008266	96.57	gold quality
esophagus squamous epithelium	UBERON:0006920	96.54	gold quality
squamous epithelium	UBERON:0006914	96.47	gold quality
epithelium of esophagus	UBERON:0001976	96.42	gold quality
tongue squamous epithelium	UBERON:0006919	96.40	gold quality
nasal cavity epithelium	UBERON:0005384	96.26	gold quality
palpebral conjunctiva	UBERON:0001812	96.16	gold quality
bone marrow	UBERON:0002371	96.16	gold quality
trabecular bone tissue	UBERON:0002483	96.06	gold quality
colonic mucosa	UBERON:0000317	95.64	gold quality
vermiform appendix	UBERON:0001154	95.60	gold quality
lower lobe of lung	UBERON:0008949	95.53	gold quality
jejunal mucosa	UBERON:0000399	95.32	gold quality
spleen	UBERON:0002106	95.27	gold quality
mucosa of urinary bladder	UBERON:0001259	95.23	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.18	gold quality
oral cavity	UBERON:0000167	95.01	gold quality
decidua	UBERON:0002450	94.95	gold quality
cervix epithelium	UBERON:0004801	94.86	gold quality
caecum	UBERON:0001153	94.63	gold quality
mammalian vulva	UBERON:0000997	94.62	gold quality
duodenum	UBERON:0002114	94.36	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	574.12
E-MTAB-7381	no	635.75
E-MTAB-6142	no	331.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CXCL1	Activation
CXCL2	Activation
IL1B	Activation

Upstream regulators (CollecTRI, top): AP1, CREM, CTCF, IFI16, IRF1, IRF6, LITAF, LRRFIP1, MTA1, NFKB, NFKBID, NR1H4, PPARG, RELA, STAT1, STAT3, STAT5A, STAT5B

miRNA regulators (miRDB)

63 targeting MYD88, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836

Literature-anchored findings (GeneRIF, showing 40)

• IFN-gamma markedly up-regulated CD14 and MyD88 but not TLR4 protein and MD-2 mRNA expression in human gingival fibroblasts. (PMID:11854210)
• Although expression levels of MyD88 mRNA and protein are normal in lipopolysaccharide (LPS)-tolerant monocytes, MyD88 fails to be recruited to TLR4 in response to LPS restimulation. (PMID:12391239)
• The MyD88 transduction signaling pathway is involved in endothelial activation by antiphospholipid antibodies. Delta MyD88 significantly abrogates antibody-induced as well as IL-1- or LPS-induced NF-kappa B activation. (PMID:12531807)
• saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4 and its downstream signaling pathways involving MyD88/IRAK/TRAF6 and PI3K/AKT. (PMID:12865424)
• an LPS-inducible splice variant of MyD88, MyD88(S), is not able to activate NF-kB, and functions as a dominant negative inhibitor of TLR/IL-1R-induced NF-kB activation. MyD88(S) still allows JNK phosphorylation and AP-1-dependent reporter gene induction (PMID:12885415)
• Mice deficient in Toll-like receptor (TLR)-2, TLR-4, TLR-2/TLR-4, and myeloid differentiation factor 88 produced the same amount of IL-6 as macrophages from normal mice. (PMID:14573621)
• MyD88 and Mal/TIRAP are essential for LPS-induced I kappa B alpha phosphorylation, NF-kappa B activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. (PMID:14630816)
• TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination. (PMID:15361868)
• TGF-beta1 can specifically interfere with TLR2, -4, or -5 ligand-induced responses involving the adaptor molecule MyD88 (myeloid differentiation factor 88) but not the TRAM/TRIF signaling pathway (PMID:15623538)
• BCG induced transcription and secretion of the chemokine CXCL8, by signalling through Toll-like receptors TLR2 and TLR4, in conjunction with myeloid differentiation factor 88 (MyD88)in neutrophils (PMID:15760459)
• activation of TLR4-MyD88-dependent and -independent signaling pathways by endotoxins determined by structure of the endotoxin (PMID:15845500)
• Analysis of a three-dimensional docking model of the TIR-TIR interaction between MyD88 and IL1RAcP (PMID:15849357)
• Monarch-1 associates with IRAK-1 but not MyD88, resulting in the blockage of IRAK-1 hyperphosphorylation (PMID:16203735)
• The adaptor MyD88 is specifically recruited to the bacterial or inclusion membrane during a productive infection with chlamydia. (PMID:16293622)
• By manipulating levels of MyD88 splicing, proinflammatory signaling through the IL-1R has been shown to be diminished, both in cell culture and in mouse liver (PMID:16517734)
• TGF-beta-activated kinase 1, TNF receptor-associated factor 6, and MyD88 are important signal transducers in H. pylori-infected human epithelial cells (PMID:16517750)
• MyD88 bridges TLR5 engagement to PI3K activation in response to flagellin (PMID:16644730)
• Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-gamma (PMID:17363736)
• IL-1RAcP, MyD88, and IRAK-4 are the stable components of the endogenous type I interleukin-1 (IL-1) receptor signaling complex (PMID:17507369)
• Data show that single-stranded RNA of HIV-1 encodes multiple uridine-rich Toll-like receptor 7/8 ligands that induce MyD88-dependent plasmacytoid dendritic cell and monocyte activation, as well as accessory cell-dependent T-cell activation. (PMID:17507480)
• TLR4 engagement by lipopolysaccharide completely fails to activate the MyD88-independent signaling pathway in human neutrophils, a feature of their terminal maturation. (PMID:17513785)
• ST2825 interfered with recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1beta-mediated activation of NF-kappaB transcriptional activity. (PMID:17548806)
• Distinct roles for the TIR and non-TIR regions in the subcellular localization and signaling properties of MyD88. (PMID:17583698)
• MyD88, IRAK1 and TRAF6 proteins are crucial early mediators for the IL-1beta-induced MMP-13 regulation through MAPK pathways and AP-1 activity. (PMID:17905570)
• MyD88dn reduced proliferation and induced apoptosis of MT2 cells (PMID:17920759)
• a role for NF-kappaB activation in the inhibition of HBV replication and suggest a novel mechanism for the inhibition of HBV replication by MyD88 protein. (PMID:17935950)
• MyD88 has a role in chemoresistance to paclitaxel in epithelial ovarian cancer (PMID:17940625)
• TRAF6 is involved but with different mechanisms in MyD88-induced activation of NF-kappaB. (PMID:18070982)
• Nitric oxide (NO) has a potential to retard induction of MyD88-dependent signaling events through the reversible and oxidative modification by NO. (PMID:18086890)
• EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2-myeloid differentiation factor 88 signaling pathway (PMID:18195069)
• MyD88 forms a complex with focal adhesion kinase (FAK) and myelin and T-cell associated maturation protein (MAL) in bacterial lipopolyssaccharide and protein I/II-activated fibroblast-like synoviocytes from rheumatoid arthitis patients. (PMID:18292575)
• scaffold protein MyD88 as the link coupling TLR2,4 to PKCepsilon recruitment, phosphorylation, and downstream signaling. (PMID:18458086)
• These results demonstrate that downregulation of IRAK-4 requires activation of the MyD88-dependent pathway and that the death domains of both MyD88 and IRAK-4 are important for this downregulation. (PMID:18503546)
• TLR4 may participate in cerebral ischemic injury through an MyD88-independent signal pathway. (PMID:18523439)
• microfilariae interfere with monocyte-derived DC function by altering TLR3 and TLR4 expression and interfering with both MyD88-dependent signaling and a pathway that ultimately diminishes NF-kappaB activity (PMID:18541719)
• PTP1B is a physiological negative regulator of TLR signaling via suppression of both MyD88- and TRIF-dependent production of proinflammatory cytokine and IFN-beta in macrophages. (PMID:18571728)
• These results suggest that TLR signaling is mediated via MyD88-independent pathways as well as MyD88-dependent pathways in human adipose tissue-derived mesenchymal stem cells. (PMID:18581201)
• study of MyD88 deficient children who had life-threatening pyogenic bacterial infection but normal resistance to other microbes;MyD88-dependent TLRs & IL-1Rs are essential for immunity to some pyogenic bacteria but redundant for defense to most infections (PMID:18669862)
• germinating but not resting conidia of A. fumigatus results in interleukin (IL)-8 synthesis that is controlled by phosphatidylinositol 3-kinase, p38 MAPK, and ERK1/2. MyD88 pathway is activated by A. fumigatus and leads to NF-kappaB activation (PMID:18703508)
• MyD88 is important in IL-6 and MMP-1 expressions in both acutely UV-irradiated skin and in chronically sun-exposed human skin (PMID:18719610)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	myd88	ENSDARG00000010169
mus_musculus	Myd88	ENSMUSG00000032508
rattus_norvegicus	Myd88	ENSRNOG00000013634
drosophila_melanogaster	Myd88	FBGN0033402

Protein

Protein identifiers

Myeloid differentiation primary response protein MyD88 — Q99836 (reviewed: Q99836)

All UniProt accessions (6): Q99836, A0A0A0MSI9, A0A3B3ITY3, A0A3F2YP85, A0A494C0J8, A0A8V8TP38

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses such as SARS-CoV-2, SARS-CoV and HIV-1, induces IL1B release through NLRP3 inflammasome activation. MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine.

Subunit / interactions. Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR5, IRAK1, IRAK2 and IRAK4 via their respective TIR domains. Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7. Interacts with LRRFIP1 and LRRFIP2; this interaction positively regulates Toll-like receptor (TLR) signaling in response to agonist. Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via H2A and OB-fold regions); this interaction is direct. Interacts with OTUD4 deubiquitinase; the interaction is direct. Interacts with TLR4. (Microbial infection) In case of infection, interacts with uropathogenic E.coli protein TcpC; suppressing Toll-like receptor (TLR)-mediated cytokine production. (Microbial infection) In case of infection, interacts with uropathogenic E.faecalis protein TcpF; suppressing Toll-like receptor (TLR)-mediated cytokine production. (Microbial infection) In case of infection, interacts with B.melitensis protein TcpB. (Microbial infection) Interacts with human metapneumovirus protein M2-2; this interaction prevents MYD88-mediated cytokine secretion. (Microbial infection) Interacts with human cytomegalovirus protein UL88; this interaction degrades MYD88 and reduces innate immune activation.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Ubiquitinated; undergoes ‘Lys-63’-linked polyubiquitination. OTUD4 specifically hydrolyzes ‘Lys-63’-linked polyubiquitinated MYD88. Deubiquitinated by USP3 that cleaves ‘Lys-63’-linked ubiquitin chains leading to inhibition of MYD88-induced NF-kappa-B signaling. (Microbial infection) Ubiquitinated by human herpesvirus 8 (KSHV) protein RTA/ORF50, leading to proteasomal degradation and suppression of TLR4 signaling pathway.

Disease relevance. Immunodeficiency 68 (IMD68) [MIM:612260] An autosomal recessive primary immunodeficiency characterized by life-threatening, often recurrent, pyogenic bacterial infections, including invasive pneumococcal disease, beginning in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry. Macroglobulinemia, Waldenstrom, 1 (WM1) [MIM:153600] A malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein. Clinical features are variable and include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Many patients have asymptomatic or indolent disease. The disease is caused by variants affecting the gene represented in this entry. Defects in MYD88 are frequently found in many hematological malignancies, such as activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL), cutaneous diffuse large B cell lymphoma (CBCL) and primary central nervous system lymphoma (PCNSL).

Domain organisation. The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.

Isoforms (6)

UniProt ID	Names	Canonical?
Q99836-1	1	yes
Q99836-2	2
Q99836-3	3
Q99836-4	4
Q99836-5	5
Q99836-6	6

RefSeq proteins (8): NP_001166037, NP_001166038, NP_001166039, NP_001166040, NP_001352805, NP_001352806, NP_001361716, NP_002459* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR000488	Death_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR017281	Myelin_different_resp_MyD88	Family
IPR034249	MyD88_Death	Domain
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily

Pfam: PF00531, PF13676

UniProt features (70 total): helix 20, sequence variant 18, strand 11, mutagenesis site 8, splice variant 6, domain 2, sequence conflict 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4EO7	X-RAY DIFFRACTION	1.45
9HFV	X-RAY DIFFRACTION	1.45
4DOM	X-RAY DIFFRACTION	1.8
9HGH	X-RAY DIFFRACTION	1.9
7BER	X-RAY DIFFRACTION	2.3
7L6W	X-RAY DIFFRACTION	2.3
8S78	ELECTRON CRYSTALLOGRAPHY	2.85
7BEQ	ELECTRON CRYSTALLOGRAPHY	3
6I3N	ELECTRON MICROSCOPY	3.1
8W8M	ELECTRON MICROSCOPY	3.28
8YYM	ELECTRON MICROSCOPY	3.3
3MOP	X-RAY DIFFRACTION	3.4
2JS7	SOLUTION NMR
2Z5V	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99836-F1	81.75	0.15

Functional residue map

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

Post-translational modifications (1): 244

Mutagenesis-validated functional residues (8):

Position	Phenotype
179	in pococurante (poc); abolished myd88-dependent sensing of most toll-like receptor (tlr) ligands.
196	reduced interaction with tirap, and strongly reduced activity. strongly reduced interaction with tirap; when associated
197	slightly reduced activity.
203	abolished interaction with e.coli tcpc without affecting ability to promote toll-like receptor (tlr)-mediated cytokine p
217	strongly reduced activity.
280	abolished interaction with e.coli tcpc without affecting ability to promote toll-like receptor (tlr)-mediated cytokine p
282	slightly reduced activity.
288	slightly reduced activity, and reduced interaction with tirap. strongly reduced interaction with tirap; when associated

Function

Pathways and Gene Ontology

Reactome pathways

44 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-209543	p75NTR recruits signalling complexes
R-HSA-3134963	DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5602680	MyD88 deficiency (TLR5)
R-HSA-5603037	IRAK4 deficiency (TLR5)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9020702	Interleukin-1 signaling
R-HSA-975110	TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome
R-HSA-975871	MyD88 cascade initiated on plasma membrane
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-1606322	ZBP1(DAI) mediated induction of type I IFNs
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System

MSigDB gene sets: 741 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_AMINE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (75): response to molecule of fungal origin (GO:0002238), leukocyte activation involved in inflammatory response (GO:0002269), neutrophil activation involved in immune response (GO:0002283), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), phagocytosis (GO:0006909), apoptotic process (GO:0006915), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), JNK cascade (GO:0007254), Toll signaling pathway (GO:0008063), induced systemic resistance (GO:0009682), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), microglia differentiation (GO:0014004), response to amine (GO:0014075), immunoglobulin mediated immune response (GO:0016064), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of type I interferon production (GO:0032481), response to peptidoglycan (GO:0032494), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-17 production (GO:0032740), positive regulation of interleukin-23 production (GO:0032747), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), toll-like receptor 4 signaling pathway (GO:0034142), toll-like receptor 5 signaling pathway (GO:0034146), toll-like receptor 8 signaling pathway (GO:0034158), toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124), interleukin-33-mediated signaling pathway (GO:0038172), defense response to bacterium (GO:0042742), defense response to protozoan (GO:0042832), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), response to amino acid (GO:0043200), skin development (GO:0043588), innate immune response (GO:0045087), response to ethanol (GO:0045471), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330)

GO Molecular Function (12): Toll binding (GO:0005121), death receptor binding (GO:0005123), interleukin-1 receptor binding (GO:0005149), Toll-like receptor binding (GO:0035325), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), TIR domain binding (GO:0070976), ATP-dependent histone chaperone activity (GO:0140674), signaling receptor binding (GO:0005102), cytokine receptor binding (GO:0005126), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), extrinsic component of plasma membrane (GO:0019897), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Diseases associated with the TLR signaling cascade	4
Cytosolic sensors of pathogen-associated DNA	2
MyD88 dependent cascade initiated on endosome	2
Immune System	2
Antigen processing-Cross presentation	1
Intracellular signaling by second messengers	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
ZBP1(DAI) mediated induction of type I IFNs	1
p75NTR signals via NF-kB	1
Negative regulation of the PI3K/AKT network	1
Interleukin-1 family signaling	1
Toll Like Receptor 9 (TLR9) Cascade	1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	3
cellular anatomical structure	3
cell surface receptor signaling pathway	2
response to nitrogen compound	2
positive regulation of cytokine production	2
protein binding	2
binding	2
response to fungus	1
response to external biotic stimulus	1
inflammatory response	1
leukocyte activation	1
myeloid cell activation involved in immune response	1
immune response	1
neutrophil activation	1
toll-like receptor signaling pathway	1
endocytosis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
MAPK cascade	1
defense response to bacterium	1
innate immune response	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
central nervous system development	1
glial cell differentiation	1
macrophage differentiation	1
B cell mediated immunity	1
cellular response to lipopolysaccharide	1
regulation of type I interferon production	1
type I interferon production	1
response to molecule of bacterial origin	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

199 interactions, top by confidence:

A	B	Type	Score
MYD88	MYD88	psi-mi:“MI:0915”(physical association)	0.960

BioGRID (205): MYD88 (Two-hybrid), IRAK4 (Two-hybrid), MYD88 (Reconstituted Complex), SPOP (Affinity Capture-MS), SPOP (Two-hybrid), MYD88 (Two-hybrid), MYD88 (Affinity Capture-Western), MYD88 (Co-localization), CYLD (Affinity Capture-Western), IRAK4 (Two-hybrid), MYD88 (Two-hybrid), SPOP (Affinity Capture-MS), MYD88 (Two-hybrid), MYD88 (Affinity Capture-RNA), UBAP1 (Affinity Capture-Western)

ESM2 similar proteins: A2TF48, A5HNF6, A8QMS7, B3SRQ2, B3Y678, B3Y679, B3Y680, B3Y681, B3Y682, B3Y683, B6CJX2, C8BKC7, F1QWA8, I3L5V6, O02697, O88879, P0CI65, P22366, P42338, P48736, P52735, Q13158, Q28DJ2, Q3UR70, Q3V3E1, Q4LBC6, Q599T9, Q5FWM2, Q5XJ85, Q60992, Q61160, Q645M6, Q6AZT7, Q6Y1S1, Q7TNH6, Q7Z494, Q7ZYP6, Q803A6, Q8BGG7, Q8BTI9

Diamond homologs: A2TF48, A5HNF6, A8QMS7, B2LT64, B3SRQ2, B3Y678, B3Y679, B3Y680, B3Y681, B3Y682, B3Y683, B6CJX2, C8BKC7, P22366, Q28DJ2, Q4LBC6, Q599T9, Q5FWM2, Q5XJ85, Q61098, Q6IA17, Q6Y1S1, Q99836, Q9DF60, Q9JLZ8, Q9R1F8, Q9V477, Q9WV82, V5NAL9, P59822, Q61730, Q9NPH3, Q13478, Q9HB75, P53355, P58727, Q2V898, Q68Y56, Q9GL65, Q9MYW3

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
TIRAP	“up-regulates activity”	MYD88	binding
MYD88	“up-regulates activity”	IRAK4	binding
MYD88	“up-regulates activity”	TRAF6	binding
MYD88	“up-regulates activity”	DHX9	binding
MYD88	“up-regulates activity”	DHX36	binding
IL1RL1	“up-regulates activity”	MYD88	binding
SRC	“up-regulates activity”	MYD88	phosphorylation
MYD88	“up-regulates activity”	IRAK1	binding
IL1R1	“up-regulates activity”	MYD88	binding
TLR4	“up-regulates activity”	MYD88	binding
MYD88	“up-regulates activity”	TRAF3	binding
TLRs	“up-regulates activity”	MYD88	binding
TLR2	“up-regulates activity”	MYD88	binding
TLR9	“up-regulates activity”	MYD88	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
IRAK4 deficiency (TLR2/4)	5	68.0×	2e-06
Interleukin-1 family signaling	5	32.4×	4e-05
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	8	29.0×	1e-07
MyD88 cascade initiated on plasma membrane	5	24.3×	9e-05
MyD88-independent TLR4 cascade	5	21.9×	1e-04
Toll Like Receptor TLR6:TLR2 Cascade	5	20.9×	1e-04
Toll Like Receptor TLR1:TLR2 Cascade	5	20.0×	2e-04
Toll Like Receptor 4 (TLR4) Cascade	6	18.8×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
MyD88-dependent toll-like receptor signaling pathway	8	166.4×	5e-14
toll-like receptor signaling pathway	8	107.0×	1e-12
interleukin-1-mediated signaling pathway	5	89.2×	1e-07
lipopolysaccharide-mediated signaling pathway	6	70.2×	3e-08
toll-like receptor 4 signaling pathway	6	70.2×	3e-08
canonical NF-kappaB signal transduction	6	48.9×	1e-07
positive regulation of interleukin-12 production	5	43.5×	5e-06
positive regulation of chemokine production	5	41.6×	5e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — CLLSLL, DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	84
Likely benign	83
Benign	7

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1323304	NM_002468.5(MYD88):c.157G>T (p.Glu53Ter)	Pathogenic
2135205	NM_002468.5(MYD88):c.256_257del (p.Val86fs)	Pathogenic
3246904	NC_000003.11:g.(?38180153)(38182777_?)del	Pathogenic
7496	NM_002468.5(MYD88):c.278T>C (p.Leu93Pro)	Pathogenic
1508469	NM_002468.5(MYD88):c.463+1G>A	Likely pathogenic

SpliceAI

904 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38139034:G:GT	donor_gain	1.0000
3:38139862:A:AG	acceptor_gain	1.0000
3:38139863:G:GG	acceptor_gain	1.0000
3:38139863:GAGGA:G	acceptor_gain	1.0000
3:38139996:TGGG:T	donor_loss	1.0000
3:38139997:GG:G	donor_gain	1.0000
3:38139998:GG:G	donor_gain	1.0000
3:38139998:GGTAA:G	donor_loss	1.0000
3:38139999:G:GG	donor_gain	1.0000
3:38139999:GTA:G	donor_loss	1.0000
3:38140000:T:A	donor_loss	1.0000
3:38140382:A:AG	acceptor_gain	1.0000
3:38140383:C:G	acceptor_gain	1.0000
3:38140383:CCCAG:C	acceptor_loss	1.0000
3:38140384:CCAG:C	acceptor_loss	1.0000
3:38140385:CAGGG:C	acceptor_loss	1.0000
3:38140386:A:T	acceptor_loss	1.0000
3:38140386:AG:A	acceptor_gain	1.0000
3:38140387:G:A	acceptor_loss	1.0000
3:38140387:GG:G	acceptor_gain	1.0000
3:38140387:GGGC:G	acceptor_gain	1.0000
3:38140387:GGGCA:G	acceptor_gain	1.0000
3:38140491:G:GT	donor_gain	1.0000
3:38140494:GTT:G	donor_gain	1.0000
3:38140495:T:G	donor_gain	1.0000
3:38140550:G:GG	donor_gain	1.0000
3:38140847:AGGT:A	donor_loss	1.0000
3:38140848:GGTAA:G	donor_loss	1.0000
3:38140850:T:G	donor_loss	1.0000
3:38139862:AGAG:A	acceptor_gain	0.9900

AlphaMissense

1913 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38140815:T:C	F235L	1.000
3:38140817:C:A	F235L	1.000
3:38140817:C:G	F235L	1.000
3:38140405:T:C	F161L	0.999
3:38140407:C:A	F161L	0.999
3:38140407:C:G	F161L	0.999
3:38140418:T:A	I165N	0.999
3:38140469:T:C	L182P	0.999
3:38140496:T:C	L191S	0.999
3:38140511:G:C	R196P	0.999
3:38140556:T:C	L211P	0.999
3:38140777:T:A	V222D	0.999
3:38140783:C:T	S224F	0.999
3:38140831:C:A	A240E	0.999
3:38141251:T:A	W286R	0.999
3:38141251:T:C	W286R	0.999
3:38140412:C:A	A163D	0.998
3:38140414:T:C	F164L	0.998
3:38140416:C:A	F164L	0.998
3:38140416:C:G	F164L	0.998
3:38140420:T:C	C166R	0.998
3:38140422:C:G	C166W	0.998
3:38140444:T:C	F174L	0.998
3:38140446:T:A	F174L	0.998
3:38140446:T:G	F174L	0.998
3:38140510:C:A	R196S	0.998
3:38140559:T:A	I212N	0.998
3:38140568:G:T	R215M	0.998
3:38140780:T:A	V223D	0.998
3:38140816:T:C	F235S	0.998

dbSNP variants (sampled 300 via entrez): RS1000026301 (3:38140764 C>G,T), RS1002094943 (3:38140607 G>T), RS1002842616 (3:38140168 G>A), RS1003022889 (3:38142096 T>C), RS1003545590 (3:38136994 C>A,G,T), RS1004141438 (3:38140314 A>G), RS1004255722 (3:38136902 C>A,G,T), RS1004507623 (3:38139886 C>A,G,T), RS1005554501 (3:38142028 G>A,T), RS1006101991 (3:38138499 C>G,T), RS1006337916 (3:38138127 C>A), RS1006526116 (3:38143323 A>AC), RS1007236319 (3:38139058 C>G), RS1007571831 (3:38139304 G>T), RS1008685567 (3:38140274 A>G)

Disease associations

OMIM: gene MIM:602170 | disease phenotypes: MIM:612260

GenCC curated gene-disease

Disease	Classification	Inheritance
pyogenic bacterial infections due to MyD88 deficiency	Strong	Autosomal recessive

Mondo (2): pyogenic bacterial infections due to MyD88 deficiency (MONDO:0012839), diffuse large B-cell lymphoma (MONDO:0018905)

Orphanet (2): OBSOLETE: Bacterial susceptibility due to TLR signaling pathway deficiency (Orphanet:183713), Diffuse large B-cell lymphoma (Orphanet:544)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000225	Gingival bleeding
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000520	Proptosis
HP:0000573	Retinal hemorrhage
HP:0000965	Cutis marmorata
HP:0000979	Purpura
HP:0000980	Pallor
HP:0001025	Urticaria
HP:0001251	Ataxia
HP:0001271	Polyneuropathy
HP:0001297	Stroke
HP:0001442	Typified by somatic mosaicism
HP:0001581	Recurrent skin infections
HP:0001635	Congestive heart failure
HP:0001744	Splenomegaly
HP:0001874	Abnormality of neutrophils
HP:0001875	Decreased total neutrophil count
HP:0001897	Normocytic anemia
HP:0001909	Leukemia
HP:0001945	Fever
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002039	Anorexia
HP:0002076	Migraine
HP:0002093	Respiratory insufficiency
HP:0002113	Pulmonary infiltrates
HP:0002202	Pleural effusion

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003875_38	Gut microbiota (bacterial taxa)	6.000000e-09
GCST005992_30	Mean corpuscular hemoglobin concentration	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0004528	mean corpuscular hemoglobin concentration

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
C567379	MYD88 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5919 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
MYD88 L265P	Ibrutinib	Lymphoplasmacytic Lymphoma	Sensitivity/Response	CIViC B	EID986
MYD88 L265P	IRAK-1/4 Inhibitor + IMG-2005-5	Lymphoplasmacytic Lymphoma	Sensitivity/Response	CIViC D	EID1641
MYD88 Overexpression	Paclitaxel	Breast Cancer	Resistance	CIViC D	EID734

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6853	Toxicity	3	fentanyl

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6853	MYD88	3	3.25	1	fentanyl
rs387907272	MYD88		0.00	0

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5,7-dimethyl-2-piperazin-1-ylquinoline-3-carbonitrile	IC50	2340 nM	US-12509465: Benzoimidazole derivatives as anticancer agents
2-(1,3-benzothiazol-2-ylsulfanyl)-N-[(E)-furan-2-ylmethylideneamino]acetamide	IC50	11800 nM	US-12509465: Benzoimidazole derivatives as anticancer agents
3-[(3-methylphenyl)methylsulfanyl]-6-thiophen-2-ylpyridazine	IC50	25500 nM	US-12509465: Benzoimidazole derivatives as anticancer agents

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects reaction, increases phosphorylation, decreases reaction, increases expression, increases reaction (+2 more)	11
Particulate Matter	decreases reaction, affects cotreatment, increases abundance, increases expression, decreases expression	5
Acetaminophen	decreases expression, affects response to substance	4
Air Pollutants	decreases expression, decreases reaction, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects expression, decreases expression	4
nickel chloride	decreases reaction, increases expression	3
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate	decreases reaction, increases expression, increases reaction	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	3
Cannabidiol	decreases expression	3
Quercetin	decreases reaction, increases expression, decreases expression	3
Cyclosporine	decreases expression, decreases methylation	3
nuciferine	decreases reaction, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
FSL-1 lipoprotein, synthetic	affects reaction, increases expression, increases secretion	2
ST2825	decreases reaction, increases expression, increases reaction, increases abundance	2
Resveratrol	decreases activity, decreases reaction, increases expression	2
Benzene	increases expression	2
Diethylhexyl Phthalate	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Doxorubicin	decreases expression, increases expression	2
Methotrexate	increases expression, affects cotreatment, decreases expression	2
Nickel	increases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Zinc Acetate	decreases reaction, increases expression, affects cotreatment, decreases expression	2
Apigenin	decreases reaction, increases expression, increases reaction	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
3-hydro-2,2,5,6-tetramethylpyrazine	decreases reaction, increases expression	1
FR900359	decreases phosphorylation	1
5-(3-(4-(4-benzylpiperazin-1-yl)-N-(4-phenylthiazol-2-yl))propanamide	decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3779231	Binding	Inhibition of Flag-tagged MyD88-HA-tagged MyD88 (unknown origin) homodimerization transfected in HEK293 cells after 7 hrs by Co-immunoprecipitation assay	Design, synthesis, and evaluation of 2-piperidone derivatives for the inhibition of β-amyloid aggregation and inflammation mediated neurotoxicity. — Bioorg Med Chem

Cellosaurus cell lines

47 cell lines: 43 cancer cell line, 4 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4213	HBL-1 [Human diffuse large B-cell lymphoma]	Cancer cell line	Male
CVCL_5J54	THP1-Dual KO-MyD	Cancer cell line	Male
CVCL_8795	OCI-Ly10	Cancer cell line	Female
CVCL_8800	OCI-Ly3	Cancer cell line	Male
CVCL_9550	SU-DHL-2	Cancer cell line	Female
CVCL_A035	BCWM.1	Cancer cell line	Female
CVCL_A442	TMD8	Cancer cell line	Male
CVCL_A8CD	293-hMyD88	Transformed cell line	Female
CVCL_A8CX	HEK-Blue-Lucia TNF-alpha	Transformed cell line	Female
CVCL_B8L2	Abcam HCT 116 MYD88 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00355199	PHASE3	COMPLETED	Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
NCT00400478	PHASE3	COMPLETED	A Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation in Patients With Aggressive B-cell Lymphoma: NHL-13
NCT00499018	PHASE3	UNKNOWN	Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
NCT00790036	PHASE3	COMPLETED	Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy
NCT00846157	PHASE3	UNKNOWN	Biocell Natural Killer Mixture in Diffuse Large B Cell Lymphoma (DLBCL) Patients
NCT01122472	PHASE3	COMPLETED	Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
NCT01148446	PHASE3	COMPLETED	R-CHOP Versus R-mini-CEOP in Elderly Patients(>65)With DLBCL
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01285765	PHASE3	COMPLETED	Evaluate a Treatment Adapted to the PET Response Compared to a Standard Treatment, for Low Risk DLBCL CD 20+ Patients
NCT01287741	PHASE3	TERMINATED	A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)
NCT01321541	PHASE3	COMPLETED	Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant
NCT01459887	PHASE3	COMPLETED	Study of Recombinant Human-Mouse Chimeric Anti-CD20 Monoclonal Antibody to Treat Non-hodgkin’s Lymphoma
NCT01510184	PHASE3	TERMINATED	Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT01852435	PHASE3	UNKNOWN	R-CEOP-90/R-CEOP-70 Versus R-CHOP-50 in the Treatment of Diffuse Large B-cell Lymphoma and Follicular Lymphoma Grade 3B
NCT02054559	PHASE3	WITHDRAWN	R-CHOP Alone vs. R-CHOP Plus Radiotherapy for Localized CD20+ DLBCL
NCT02128061	PHASE3	COMPLETED	Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
NCT02268045	PHASE3	COMPLETED	Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin’s Lymphoma
NCT02366663	PHASE3	TERMINATED	BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL
NCT02449265	PHASE3	UNKNOWN	Efficacy of Consolidative Involved-site Radiotherapy for Patients With Limited-stage Diffuse Large B-cell Lymphoma
NCT02449278	PHASE3	UNKNOWN	The Palliative Benefit of Involved-site Radiotherapy for Patients With Advanced-stage Diffuse Large B-cell Lymphoma
NCT02531841	PHASE3	UNKNOWN	High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma
NCT02617485	PHASE3	COMPLETED	MabionCD20 Compared to MabThera in Lymphoma Patients
NCT02767674	PHASE3	UNKNOWN	Trial of R-GemOx Versus R-miniCHOP Regimen in First-line Treatment of Elderly Diffuse Large B Cell Lymphoma
NCT02772822	PHASE3	UNKNOWN	A Study Comparing the Efficiency and Safety of S-CHOP(Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone) Versus R-CHOP in Untreated CD20(Cluster of Differentiation Antigen 20)-Positive DLBCL Patients
NCT02777736	PHASE3	UNKNOWN	CNS Prophylaxis in Diffuse Large B-cell Lymphoma
NCT02842931	PHASE3	UNKNOWN	R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis
NCT02951156	PHASE3	TERMINATED	Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
NCT03123718	PHASE3	UNKNOWN	High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL
NCT03151044	PHASE3	UNKNOWN	R±CEOP90 Versus R±CEOP75 in Newly Diagnosed Young Patients With Medium/High-risk DLBCL
NCT03213977	PHASE3	UNKNOWN	R-DA-EDOCH Versus R-CEOP90, With/Without Upfront Auto-HSCT in Young Patients With High-risk DLBCL