TISIDB

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
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	PF05965 F/Y rich C-terminus PF05964 F/Y-rich N-terminus PF00628 PHD-finger PF00856 SET domain
Function	Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.

> Gene Ontology [ TOP ]
Biological Process	GO:0001555 oocyte growth GO:0006342 chromatin silencing GO:0006479 protein methylation GO:0007281 germ cell development GO:0007292 female gamete generation GO:0008213 protein alkylation GO:0009755 hormone-mediated signaling pathway GO:0009994 oocyte differentiation GO:0016049 cell growth GO:0016458 gene silencing GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018205 peptidyl-lysine modification GO:0022412 cellular process involved in reproduction in multicellular organism GO:0030518 intracellular steroid hormone receptor signaling pathway GO:0030520 intracellular estrogen receptor signaling pathway GO:0030522 intracellular receptor signaling pathway GO:0032259 methylation GO:0033143 regulation of intracellular steroid hormone receptor signaling pathway GO:0033145 positive regulation of intracellular steroid hormone receptor signaling pathway GO:0033146 regulation of intracellular estrogen receptor signaling pathway GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway GO:0034968 histone lysine methylation GO:0040029 regulation of gene expression, epigenetic GO:0043401 steroid hormone mediated signaling pathway GO:0043414 macromolecule methylation GO:0043627 response to estrogen GO:0045814 negative regulation of gene expression, epigenetic GO:0048477 oogenesis GO:0048545 response to steroid hormone GO:0048588 developmental cell growth GO:0048599 oocyte development GO:0051568 histone H3-K4 methylation GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound GO:1904837 beta-catenin-TCF complex assembly
Molecular Function	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:0042800 histone methyltransferase activity (H3-K4 specific)
Cellular Component	GO:0034708 methyltransferase complex GO:0035097 histone methyltransferase complex GO:0044666 MLL3/4 complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00310 Lysine degradation
Reactome	R-HSA-5619507: Activation of HOX genes during differentiation R-HSA-5617472: Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-3769402: Deactivation of the beta-catenin transactivating complex R-HSA-1266738: Developmental Biology R-HSA-201722: Formation of the beta-catenin R-HSA-3214841: PKMTs methylate histone lysines R-HSA-162582: Signal Transduction R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa00310 Lysine degradation

Reactome

R-HSA-5619507: Activation of HOX genes during differentiation
R-HSA-5617472: Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-3769402: Deactivation of the beta-catenin transactivating complex
R-HSA-1266738: Developmental Biology
R-HSA-201722: Formation of the beta-catenin
R-HSA-3214841: PKMTs methylate histone lysines
R-HSA-162582: Signal Transduction
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KMT2D 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 [ TOP ]
There is no record.

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
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 KMT2D 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	logFC: -2.69; FDR: 0.01650	Resistant to T cell-mediated killing
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	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
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 KMT2D 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	0.184	0.436
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.447	0.729
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.008	0.993
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.179	0.501
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.261	0.938
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.078	0.986
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.434	0.291
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.553	0.754
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.336	0.862
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.327	0.334
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	1.564	0.437
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.067	0.169

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KMT2D 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	21.4	5.9	15.5	0.304
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	33.3	-13.3	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	0	0	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	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	23.8	11.8	12	0.427
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	37.5	0	37.5	0.209
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	18.2	-2.8	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	44.4	18.8	25.6	0.205
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	60	22.2	37.8	0.266
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	14.3	10.7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	21.1	3.7	17.4	0.0687
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	22.7	7.7	15	0.377
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	18.8	0	18.8	0.228
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KMT2D. 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	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KMT2D. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KMT2D. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KMT2D. 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	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KMT2D expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KMT2D and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KMT2D
Name	lysine (K)-specific methyltransferase 2D
Aliases	CAGL114; TNRC21; trinucleotide repeat containing 21; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; KA ......
Chromosomal Location	12q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KMT2D collected from DrugBank database.

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

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