TISIDB

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
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 ; SUBCELLULAR LOCATION: MLL cleavage product N320: Nucleus.; SUBCELLULAR LOCATION: MLL cleavage product C180: Nucleus. Note=Localizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320.
Domain	PF05965 F/Y rich C-terminus PF05964 F/Y-rich N-terminus PF00628 PHD-finger PF00856 SET domain PF02008 CXXC zinc finger domain
Function	Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (PubMed:12453419, PubMed:20677832, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis. Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001894 tissue homeostasis GO:0003002 regionalization GO:0006304 DNA modification GO:0006305 DNA alkylation GO:0006306 DNA methylation GO:0006473 protein acetylation GO:0006475 internal protein amino acid acetylation GO:0006479 protein methylation GO:0007389 pattern specification process GO:0007611 learning or memory GO:0007612 learning GO:0007623 circadian rhythm GO:0007632 visual behavior GO:0008213 protein alkylation GO:0008306 associative learning GO:0008542 visual learning GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0009791 post-embryonic development GO:0009952 anterior/posterior pattern specification GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0016570 histone modification GO:0016571 histone methylation GO:0016573 histone acetylation GO:0018022 peptidyl-lysine methylation GO:0018023 peptidyl-lysine trimethylation GO:0018026 peptidyl-lysine monomethylation GO:0018027 peptidyl-lysine dimethylation GO:0018205 peptidyl-lysine modification GO:0018393 internal peptidyl-lysine acetylation GO:0018394 peptidyl-lysine acetylation GO:0031056 regulation of histone modification GO:0031058 positive regulation of histone modification GO:0031060 regulation of histone methylation GO:0031062 positive regulation of histone methylation GO:0032259 methylation GO:0032409 regulation of transporter activity GO:0032411 positive regulation of transporter activity GO:0032922 circadian regulation of gene expression GO:0034968 histone lysine methylation GO:0035065 regulation of histone acetylation GO:0035162 embryonic hemopoiesis GO:0035640 exploration behavior GO:0035690 cellular response to drug GO:0035864 response to potassium ion GO:0042391 regulation of membrane potential GO:0042493 response to drug GO:0043414 macromolecule methylation GO:0043543 protein acylation GO:0043966 histone H3 acetylation GO:0043967 histone H4 acetylation GO:0043970 histone H3-K9 acetylation GO:0043974 histone H3-K27 acetylation GO:0043984 histone H4-K16 acetylation GO:0044154 histone H3-K14 acetylation GO:0044648 histone H3-K4 dimethylation GO:0044708 single-organism behavior GO:0044728 DNA methylation or demethylation GO:0048167 regulation of synaptic plasticity GO:0048168 regulation of neuronal synaptic plasticity GO:0048172 regulation of short-term neuronal synaptic plasticity GO:0048511 rhythmic process GO:0048536 spleen development GO:0048568 embryonic organ development GO:0048871 multicellular organismal homeostasis GO:0048872 homeostasis of number of cells GO:0048873 homeostasis of number of cells within a tissue GO:0050804 modulation of synaptic transmission GO:0050890 cognition GO:0051568 histone H3-K4 methylation GO:0051569 regulation of histone H3-K4 methylation GO:0051571 positive regulation of histone H3-K4 methylation GO:0051899 membrane depolarization GO:0060216 definitive hemopoiesis GO:0060249 anatomical structure homeostasis GO:0061647 histone H3-K9 modification GO:0071440 regulation of histone H3-K14 acetylation GO:0080182 histone H3-K4 trimethylation GO:1901674 regulation of histone H3-K27 acetylation GO:1901983 regulation of protein acetylation GO:1902275 regulation of chromatin organization GO:1905269 positive regulation of chromatin organization GO:2000615 regulation of histone H3-K9 acetylation GO:2000756 regulation of peptidyl-lysine acetylation GO:2001023 regulation of response to drug GO:2001025 positive regulation of response to drug GO:2001038 regulation of cellular response to drug GO:2001040 positive regulation of cellular response to drug
Molecular Function	GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0003680 AT DNA 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:0042393 histone binding GO:0042800 histone methyltransferase activity (H3-K4 specific) GO:0045322 unmethylated CpG binding GO:0070577 lysine-acetylated histone binding
Cellular Component	GO:0034708 methyltransferase complex GO:0035097 histone methyltransferase complex GO:0044665 MLL1/2 complex GO:0071339 MLL1 complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00310 Lysine degradation
Reactome	R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-3214841: PKMTs methylate histone lysines

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KMT2A 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 KMT2A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28131992	Pancreatic Carcinoma	Inhibit immunity (T cell function)	The Fas-FasL/CTLs and the MLL1-H3K4me3-PD-L1 axis play contrasting roles in pancreatic cancer immune surveillance and evasion.
23014531	Leukemia	Inhibit immunity (NK cell function)	Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell-resistant MLL-rearranged leukemias.

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
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 KMT2A 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	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
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 KMT2A 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	-0.172	0.484
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.052	0.962
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.258	0.748
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.144	0.6
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.106	0.97
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.191	0.958
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.169	0.644
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.423	0.808
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.11	0.955
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.285	0.817
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	1.026	0.535
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.047	0.391

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of KMT2A 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	14.8	6.8	8	0.247
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	14.8	8.5	6.3	0.453
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	33.3	12.5	20.8	0.312
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	22.2	-2.2	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	0	50	0.109
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	15.4	-10.9	0.541
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	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	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KMT2A. 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	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KMT2A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KMT2A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KMT2A. 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	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KMT2A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KMT2A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KMT2A
Name	lysine (K)-specific methyltransferase 2A
Aliases	HRX; ALL-1; HTRX1; CXXC7; MLL1A; MLL; myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) hom ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KMT2A collected from DrugBank database.

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

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