TISIDB

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
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 Multi-pass membrane protein Early endosome membrane Multi-pass membrane protein Recycling endosome membrane Multi-pass membrane protein Note=Co-localizes with PD-L1/CD274 in the plasma membrane and in recycling endosomes.
Domain	PF01284 Membrane-associating domain
Function	Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its STUB1-mediated ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy.

> Gene Ontology [ TOP ]
Biological Process	-
Molecular Function	GO:0005125 cytokine activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CMTM6 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 CMTM6 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28813417	Melanoma	Inhibit immunity	CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo.

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
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 CMTM6 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	Second most enriched score: 0.8	Sensitive to T cell-mediated killing
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	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
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 CMTM6 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	0.028	0.909
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.067	0.98
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.103	0.956
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.188	0.681
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.181	0.913
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.195	0.924
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.044	0.926
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.016	0.994
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.134	0.953
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.027	0.985
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	0.417	0.849
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.121	0.2

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CMTM6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CMTM6. 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	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CMTM6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CMTM6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CMTM6. 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	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CMTM6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CMTM6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CMTM6
Name	CKLF-like MARVEL transmembrane domain containing 6
Aliases	FLJ20396; CKLFSF6; chemokine-like factor super family 6; chemokine-like factor superfamily 6; PRO2219; chemo ......
Chromosomal Location	3p22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CMTM6 collected from DrugBank database.

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

Browse CMTM6