TISIDB

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
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	Nucleus
Domain	PF02373 JmjC domain
Function	Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000302 response to reactive oxygen species GO:0001704 formation of primary germ layer GO:0001707 mesoderm formation GO:0002437 inflammatory response to antigenic stimulus GO:0003158 endothelium development GO:0006482 protein demethylation GO:0006979 response to oxidative stress GO:0007369 gastrulation GO:0007498 mesoderm development GO:0007507 heart development GO:0008214 protein dealkylation GO:0009636 response to toxic substance GO:0010035 response to inorganic substance GO:0014706 striated muscle tissue development GO:0014823 response to activity GO:0016570 histone modification GO:0016577 histone demethylation GO:0021537 telencephalon development GO:0021543 pallium development GO:0021761 limbic system development GO:0021766 hippocampus development GO:0030900 forebrain development GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0035051 cardiocyte differentiation GO:0042542 response to hydrogen peroxide GO:0042692 muscle cell differentiation GO:0045165 cell fate commitment GO:0045446 endothelial cell differentiation GO:0048332 mesoderm morphogenesis GO:0048333 mesodermal cell differentiation GO:0048738 cardiac muscle tissue development GO:0051146 striated muscle cell differentiation GO:0055007 cardiac muscle cell differentiation GO:0060537 muscle tissue development GO:0060992 response to fungicide GO:0070076 histone lysine demethylation GO:0070301 cellular response to hydrogen peroxide GO:0070988 demethylation GO:0071557 histone H3-K27 demethylation
Molecular Function	GO:0003682 chromatin binding GO:0008013 beta-catenin binding GO:0032451 demethylase activity GO:0032452 histone demethylase activity GO:0051213 dioxygenase activity GO:0071558 histone demethylase activity (H3-K27 specific)
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-3214842: HDMs demethylate histones R-HSA-2559580: Oxidative Stress Induced Senescence

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KDM6B 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 KDM6B and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26567139	Colon Carcinoma	Inhibit immunity (infiltration)	We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival.

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
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 KDM6B 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	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
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 KDM6B 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	-0.039	0.881
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.62	0.626
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.381	0.706
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.472	0.211
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.609	0.828
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.293	0.938
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.31	0.393
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.357	0.791
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.277	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.621	0.485
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	1.159	0.33
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.128	0.135

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KDM6B 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	14.3	0	14.3	0.196
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	3.7	4.1	-0.4	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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	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	15.4	9.1	6.3	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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KDM6B. 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	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KDM6B. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KDM6B. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KDM6B. 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	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KDM6B expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KDM6B and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KDM6B
Name	lysine (K)-specific demethylase 6B
Aliases	KIAA0346; JMJD3; jumonji domain containing 3; jumonji domain containing 3, histone lysine demethylase; jmjC ......
Chromosomal Location	17p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KDM6B collected from DrugBank database.

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

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