TISIDB

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Nucleus
Domain	PF00531 Death domain PF01582 TIR domain
Function	Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:24316379, PubMed:19506249). Increases IL-8 transcription (PubMed:9013863). 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. 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 (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0009612 response to mechanical stimulus GO:0010608 posttranscriptional regulation of gene expression GO:0031349 positive regulation of defense response GO:0032479 regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032606 type I interferon production GO:0032620 interleukin-17 production GO:0032627 interleukin-23 production GO:0032635 interleukin-6 production GO:0032660 regulation of interleukin-17 production GO:0032667 regulation of interleukin-23 production GO:0032675 regulation of interleukin-6 production GO:0032740 positive regulation of interleukin-17 production GO:0032747 positive regulation of interleukin-23 production GO:0032755 positive regulation of interleukin-6 production GO:0034162 toll-like receptor 9 signaling pathway GO:0042742 defense response to bacterium GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043487 regulation of RNA stability GO:0043488 regulation of mRNA stability GO:0043489 RNA stabilization GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0048255 mRNA stabilization GO:0050727 regulation of inflammatory response GO:0050830 defense response to Gram-positive bacterium GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0070555 response to interleukin-1 GO:0070935 3'-UTR-mediated mRNA stabilization GO:0071214 cellular response to abiotic stimulus GO:0071260 cellular response to mechanical stimulus GO:0071496 cellular response to external stimulus GO:0098542 defense response to other organism
Molecular Function	GO:0005123 death receptor binding GO:0005126 cytokine receptor binding GO:0032813 tumor necrosis factor receptor superfamily binding GO:0043621 protein self-association GO:0070976 TIR domain binding
Cellular Component	GO:0010008 endosome membrane GO:0044440 endosomal part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04064 NF-kappa B signaling pathway hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-1280218: Adaptive Immune System R-HSA-1236975: Antigen processing-Cross presentation R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA R-HSA-3134963: DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-HSA-1643685: Disease R-HSA-5602358: Diseases associated with the TLR signaling cascade R-HSA-5260271: Diseases of Immune System R-HSA-1236974: ER-Phagosome pathway R-HSA-5603041: IRAK4 deficiency (TLR2/4) R-HSA-5603037: IRAK4 deficiency (TLR5) R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-446652: Interleukin-1 signaling R-HSA-975871: MyD88 cascade initiated on plasma membrane R-HSA-5602498: MyD88 deficiency (TLR2/4) R-HSA-5602680: MyD88 deficiency (TLR5) R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-166058: MyD88 R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-1810476: RIP-mediated NFkB activation via ZBP1 R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-166520: Signalling by NGF R-HSA-445989: TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines R-HSA-933541: TRAF6 mediated IRF7 activation R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-933542: TRAF6 mediated NF-kB activation R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades R-HSA-1606322: ZBP1(DAI) mediated induction of type I IFNs R-HSA-193704: p75 NTR receptor-mediated signalling R-HSA-209543: p75NTR recruits signalling complexes R-HSA-193639: p75NTR signals via NF-kB

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04064 NF-kappa B signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-1280218: Adaptive Immune System
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-3134963: DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-1643685: Disease
R-HSA-5602358: Diseases associated with the TLR signaling cascade
R-HSA-5260271: Diseases of Immune System
R-HSA-1236974: ER-Phagosome pathway
R-HSA-5603041: IRAK4 deficiency (TLR2/4)
R-HSA-5603037: IRAK4 deficiency (TLR5)
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-446652: Interleukin-1 signaling
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-5602498: MyD88 deficiency (TLR2/4)
R-HSA-5602680: MyD88 deficiency (TLR5)
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-166058: MyD88
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-1810476: RIP-mediated NFkB activation via ZBP1
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-166520: Signalling by NGF
R-HSA-445989: TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-1606322: ZBP1(DAI) mediated induction of type I IFNs
R-HSA-193704: p75 NTR receptor-mediated signalling
R-HSA-209543: p75NTR recruits signalling complexes
R-HSA-193639: p75NTR signals via NF-kB

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MYD88 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between MYD88 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23184679	Colon carcinoma	Inhibit immunity	However, MDSCs obtained from tumor-bearing Myd88(-/-) mice failed to suppress antigen-specific proliferation of CD8(+) T cells and CD4(+) T cells, whereas MDSCs from wild-type mice significantly suppressed both types of T cells. Consistent with this, we found that the levels of costimulatory molecules and MHC class II were significantly increased in MDSCs obtained from Myd88(-/-) mice compared with wild-type mice after tumor challenge. Finally, the blockade of Myd88 signaling by treatment with Myd88 inhibitory peptide, during later tumor stages, significantly inhibited the growth of immunogenic tumors.
17363736	Multiple Myeloma-IgG	Inhibit immunity (T cell function)	We observed that B7-H1 was expressed in most MM plasma cells, but not cells isolated from monoclonal gammopathy of undetermined significance or healthy donors. This expression was increased or induced by IFN-gamma and Toll-like receptor (TLR) ligands in isolated MM plasma cells. Blocking the MEK/ERK pathway inhibited IFN-gamma-mediated and TLR-mediated expression of B7-H1. 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. IFN-gamma-induced STAT1 activation, via MEK/ERK and MyD88/TRAF6, and inhibition of STAT1 reduced B7-H1 expression. MM plasma cells stimulated with IFN-gamma or TLR ligands inhibited cytotoxic T lymphocytes (CTLs) generation and this immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, the UO126 MEK inhibitor, or by transfection of a dominant-negative mutant of MyD88.
20823152	Colon Carcinoma; Colorectal Carcinoma; Melanoma; Breast Carcinoma	Promote immunity (T cell function)	Importantly, in vivo intratumoral injection of Ad-MyD88 into established tumor masses enhanced adaptive immune responses and inhibited local tumor immunosuppression, resulting in significantly inhibited local and systemic growth of multiple tumor types. Finally, Ad-MyD88 infection of primary human dendritic cells, tumor-associated fibroblasts, and colorectal carcinoma cells elicited significant Th1-type cytokine responses, resulting in enhanced tumor cell lysis and expansion of human tumor antigen-specific T cells.
29653983	squamous cell carcinoma	Promote immunity (T cell function); essential for immunotherapy	In mice with wild-type caspase-1, MyD88-silenced tumors displayed reduced growth rate, but in chimeric mice with caspase-1 null bone marrow cells, MyD88-silenced tumors did not display differential tumor growth rate.
28011934	Melanoma	Promote immunity	Specifically, MyD88, an essential component of the IL-33 signaling pathway, was required for the IL-33-mediated increase in mDC number and upregulation in expression of costimulatory molecules.

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of MYD88 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of MYD88 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.214	0.365
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.136	0.95
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.268	0.862
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.567	0.229
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.415	0.789
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.768	0.724
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.047	0.909
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.004	0.998
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.033	0.986
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.736	0.626
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.618	0.795
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.069	0.334

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MYD88 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MYD88. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MYD88. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MYD88. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MYD88. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MYD88 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MYD88 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MYD88
Name	myeloid differentiation primary response 88
Aliases	myeloid differentiation primary response gene (88); MYD88D; Myeloid differentiation primary response protein ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MYD88 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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