TISIDB

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
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 Chromosome Note=Associates with euchromatic regions. Does not associate with heterochromatin.
Domain	PF12796 Ankyrin repeats (3 copies) PF05033 Pre-SET motif PF00856 SET domain
Function	Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.

> Gene Ontology [ TOP ]
Biological Process	GO:0006260 DNA replication GO:0006275 regulation of DNA replication GO:0006304 DNA modification GO:0006305 DNA alkylation GO:0006306 DNA methylation GO:0006479 protein methylation GO:0008213 protein alkylation GO:0009267 cellular response to starvation GO:0009991 response to extracellular stimulus GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018027 peptidyl-lysine dimethylation GO:0018205 peptidyl-lysine modification GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0032259 methylation GO:0034968 histone lysine methylation GO:0042594 response to starvation GO:0043414 macromolecule methylation GO:0044728 DNA methylation or demethylation GO:0051052 regulation of DNA metabolic process GO:0051567 histone H3-K9 methylation GO:0061647 histone H3-K9 modification GO:0070734 histone H3-K27 methylation GO:0071496 cellular response to external stimulus GO:0072331 signal transduction by p53 class mediator GO:1901796 regulation of signal transduction by p53 class mediator
Molecular Function	GO:0002039 p53 binding GO:0003682 chromatin binding GO:0008168 methyltransferase activity GO:0008170 N-methyltransferase activity GO:0008276 protein methyltransferase activity GO:0008757 S-adenosylmethionine-dependent methyltransferase activity GO:0016278 lysine N-methyltransferase activity GO:0016279 protein-lysine N-methyltransferase activity GO:0016741 transferase activity, transferring one-carbon groups GO:0018024 histone-lysine N-methyltransferase activity GO:0042054 histone methyltransferase activity GO:0046974 histone methyltransferase activity (H3-K9 specific) GO:0046976 histone methyltransferase activity (H3-K27 specific) GO:0070742 C2H2 zinc finger domain binding GO:1990841 promoter-specific chromatin binding
Cellular Component	GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00310 Lysine degradation
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-427389: ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression R-HSA-212165: Epigenetic regulation of gene expression R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-3214841: PKMTs methylate histone lysines R-HSA-5250913: Positive epigenetic regulation of rRNA expression R-HSA-73854: RNA Polymerase I Promoter Clearance R-HSA-73864: RNA Polymerase I Transcription R-HSA-73762: RNA Polymerase I Transcription Initiation R-HSA-504046: RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804760: Regulation of TP53 Activity through Methylation R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP) R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

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KEGG

hsa00310 Lysine degradation

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-427389: ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-212165: Epigenetic regulation of gene expression
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-3214841: PKMTs methylate histone lysines
R-HSA-5250913: Positive epigenetic regulation of rRNA expression
R-HSA-73854: RNA Polymerase I Promoter Clearance
R-HSA-73864: RNA Polymerase I Transcription
R-HSA-73762: RNA Polymerase I Transcription Initiation
R-HSA-504046: RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804760: Regulation of TP53 Activity through Methylation
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between EHMT2 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 EHMT2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23312906	Glioma; Mesothelioma	Promote immunity	In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes.The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies.

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
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 EHMT2 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	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
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 EHMT2 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	0.142	0.582
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.086	0.901
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.177	0.777
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.173	0.555
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.699	0.787
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.498	0.873
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.203	0.541
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.251	0.874
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.171	0.921
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.51	0.754
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	0.759	0.744
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.192	0.00441

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of EHMT2 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	5.9	1.2	1
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	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
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	7.4	3.4	4	0.587
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	33.3	12.5	20.8	0.312
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	40	22.2	17.8	0.58
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
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	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EHMT2. 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	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EHMT2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EHMT2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EHMT2. 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	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EHMT2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EHMT2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EHMT2
Name	euchromatic histone-lysine N-methyltransferase 2
Aliases	G9A; Em:AF134726.3; NG36/G9a; KMT1C; C6orf30; BAT8; chromosome 6 open reading frame 30; HLA-B associated tra ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EHMT2 collected from DrugBank database.

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

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