TISIDB

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
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 II membrane protein
Domain	PF00059 Lectin C-type domain
Function	C-type lectin that functions as cell-surface receptor for a wide variety of ligands such as damaged cells, fungi and mycobacteria. Plays a role in the recognition of pathogenic fungi, such as Candida albicans. The detection of mycobacteria is via trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid. Specifically recognizes alpha-mannose residues on pathogenic fungi of the genus Malassezia. Recognizes also SAP130, a nuclear protein, that is released by dead or dying cells. Transduces signals through an ITAM-containing adapter protein, Fc receptor gamma chain /FCER1G. Induces secretion of inflammatory cytokines through a pathway that depends on SYK, CARD9 and NF-kappa-B.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002220 innate immune response activating cell surface receptor signaling pathway GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002286 T cell activation involved in immune response GO:0002292 T cell differentiation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002521 leukocyte differentiation GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0007159 leukocyte cell-cell adhesion GO:0009306 protein secretion GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0031349 positive regulation of defense response GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0042110 T cell activation GO:0042742 defense response to bacterium GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0098542 defense response to other organism GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0030246 carbohydrate binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5621480: Dectin-2 family R-HSA-168256: Immune System R-HSA-168249: Innate Immune System

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CLEC4E 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 CLEC4E and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27049944	Pancreatic Ductal Adenocarcinoma	Inhibit immunity	Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
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 CLEC4E 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	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
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 CLEC4E 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	-0.445	0.196
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.072	0.907
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.725	0.192
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.703	0.166
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.358	0.193
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.125	0.922
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.387	0.557
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.217	0.218
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.418	0.682
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.208	0.149
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	1.054	0.433
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.07	0.794

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CLEC4E 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	0	4.1	-4.1	0.561
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	5.1	-5.1	0.549
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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	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	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
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	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CLEC4E. 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	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CLEC4E. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CLEC4E. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CLEC4E. 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	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CLEC4E expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CLEC4E and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CLEC4E
Name	C-type lectin domain family 4, member E
Aliases	mincle; CLECSF9; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; C ......
Chromosomal Location	12p13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CLEC4E collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CLEC4E.

ID	Name	Drug Type	Targets	#Targets
DB04540	Cholesterol	Small Molecule	CLEC4E, NR1I3, RORA, VDR	4

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