TISIDB

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
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	Cell membrane Single-pass type I membrane protein. Golgi apparatus Cell surface
Domain	PF09067 Erythropoietin receptor PF00041 Fibronectin type III domain
Function	Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

> Gene Ontology [ TOP ]
Biological Process	GO:0001666 response to hypoxia GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0007596 blood coagulation GO:0007599 hemostasis GO:0030168 platelet activation GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0034109 homotypic cell-cell adhesion GO:0036293 response to decreased oxygen levels GO:0036294 cellular response to decreased oxygen levels GO:0038163 thrombopoietin-mediated signaling pathway GO:0046651 lymphocyte proliferation GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050817 coagulation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050878 regulation of body fluid levels GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0070098 chemokine-mediated signaling pathway GO:0070482 response to oxygen levels GO:0070527 platelet aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0071453 cellular response to oxygen levels GO:0071456 cellular response to hypoxia
Molecular Function	GO:0004896 cytokine receptor activity GO:0038164 thrombopoietin receptor activity
Cellular Component	GO:0043025 neuronal cell body GO:0044297 cell body

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04630 Jak-STAT signaling pathway
Reactome	R-HSA-109582: Hemostasis R-HSA-76009: Platelet Aggregation (Plug Formation) R-HSA-76002: Platelet activation, signaling and aggregation

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MPL 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 MPL and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25252915	Lung Carcinoma	Promote immunity (T cell function)	In the metastatic model of Lewis lung carcinoma, vaccination of the TAA survivin with SA-4-1BBL/MPL yielded superior efficacy against pulmonary metastases. Therapeutic efficacy of SA-4-1BBL/MPL was achieved in the absence of detectable toxicity, correlating with enhanced dendritic cell activation, CD8(+) T-cell function, and an increased intratumoral ratio of CD8(+) T effector cells to CD4(+)FoxP3(+) T regulatory cells.

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
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 MPL 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	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
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 MPL 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.559	0.244
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.282	0.827
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.902	0.601
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.218	0.121

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MPL 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	0	7.1	0.452
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	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
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	18.2	-18.2	0.199
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	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MPL. 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	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MPL. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MPL. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MPL. 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	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MPL expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MPL and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MPL
Name	MPL proto-oncogene, thrombopoietin receptor
Aliases	CD110; TPOR; myeloproliferative leukemia virus oncogene; C-MPL; CD110V; THCYT2; TPO-R; myeloproliferative le ......
Chromosomal Location	1p34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MPL collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MPL.

ID	Name	Drug Type	Targets	#Targets
DB05332	Romiplostim	Biotech	MPL	1
DB05930	SB-559448	Small Molecule	MPL	1
DB06210	Eltrombopag	Small Molecule	MPL	1
DB06534	Thrombopoietin	Biotech	MPL	1

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