TISIDB

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
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	Membrane; Single-pass type I membrane protein.
Domain	PF12662 Complement Clr-like EGF-like PF07645 Calcium-binding EGF domain PF00059 Lectin C-type domain PF09064 Thrombomodulin like fifth domain
Function	Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.

> Gene Ontology [ TOP ]
Biological Process	GO:0002237 response to molecule of bacterial origin GO:0007565 female pregnancy GO:0007596 blood coagulation GO:0007599 hemostasis GO:0009314 response to radiation GO:0010165 response to X-ray GO:0010212 response to ionizing radiation GO:0010543 regulation of platelet activation GO:0010544 negative regulation of platelet activation GO:0014074 response to purine-containing compound GO:0030168 platelet activation GO:0030193 regulation of blood coagulation GO:0030194 positive regulation of blood coagulation GO:0030195 negative regulation of blood coagulation GO:0032102 negative regulation of response to external stimulus GO:0032103 positive regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0042730 fibrinolysis GO:0044706 multi-multicellular organism process GO:0046683 response to organophosphorus GO:0050817 coagulation GO:0050818 regulation of coagulation GO:0050819 negative regulation of coagulation GO:0050820 positive regulation of coagulation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050878 regulation of body fluid levels GO:0050900 leukocyte migration GO:0051591 response to cAMP GO:0051917 regulation of fibrinolysis GO:0051918 negative regulation of fibrinolysis GO:0061041 regulation of wound healing GO:0061045 negative regulation of wound healing GO:0090303 positive regulation of wound healing GO:1900046 regulation of hemostasis GO:1900047 negative regulation of hemostasis GO:1900048 positive regulation of hemostasis GO:1903034 regulation of response to wounding GO:1903035 negative regulation of response to wounding GO:1903036 positive regulation of response to wounding
Molecular Function	-
Cellular Component	GO:0016327 apicolateral plasma membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-202733: Cell surface interactions at the vascular wall R-HSA-140875: Common Pathway of Fibrin Clot Formation R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade) R-HSA-109582: Hemostasis

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between THBD 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 THBD and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25046660	Leukemia	Promote immunity	Taken together, our findings point toward a novel role of human NK cells bridging innate and adaptive immunity through selective induction of cell-associated Ag cross-presentation by CD141(high) DC, a process that could be exploited to better harness Ag-specific cellular immunity in immunotherapy.
29664013	melanoma	Promote immunity	This poor-prognosis subgroup exhibited expression profiles consistent with β-catenin-mediated failure to recruit CD141+ DCs.

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
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 THBD 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	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
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 THBD 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	-0.213	0.682
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.251	0.87
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.177	0.87
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.848	0.203
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.194	0.586
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.414	0.878
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.229	0.665
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.327	0.807
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.146	0.919
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.963	0.416
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	2.057	0.208
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.769	2.59e-05

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of THBD 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	7.1	17.6	-10.5	0.607
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	14.3	10.7	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	7.9	0	7.9	0.26
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	12.5	0	12.5	0.485
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	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of THBD. 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	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of THBD. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by THBD. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of THBD. 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	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of THBD expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between THBD and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	THBD
Name	thrombomodulin
Aliases	CD141; AHUS6; BDCA3; THPH12; THRM; CD141 antigen; fetomodulin; CD antigen CD141
Chromosomal Location	20p11.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting THBD collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting THBD.

ID	Name	Drug Type	Targets	#Targets
DB00055	Drotrecogin alfa	Biotech	CP, F2, F5, F8, GGCX, PF4, PROCR, PROS1, SERPINA5, SERPINB6, SERPI ......	12
DB01050	Ibuprofen	Small Molecule	BCL2, CFTR, FABP2, PLAT, PPARA, PPARG, PTGS1, PTGS2, SLC15A1, THBD	10
DB09213	Dexibuprofen	Small Molecule	BCL2, CFTR, FABP2, PLAT, PPARG, PTGS1, PTGS2, THBD	8

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