TISIDB

Summary
Symbol	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
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
Domain	PF00856 SET domain PF08236 SRI (Set2 Rpb1 interacting) domain PF00397 WW domain
Function	Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). ; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.

> Gene Ontology [ TOP ]
Biological Process	GO:0001501 skeletal system development GO:0001525 angiogenesis GO:0001570 vasculogenesis GO:0001701 in utero embryonic development GO:0001763 morphogenesis of a branching structure GO:0001838 embryonic epithelial tube formation GO:0001841 neural tube formation GO:0001843 neural tube closure GO:0001890 placenta development GO:0001892 embryonic placenta development GO:0006298 mismatch repair GO:0006354 DNA-templated transcription, elongation GO:0006368 transcription elongation from RNA polymerase II promoter GO:0006403 RNA localization GO:0006405 RNA export from nucleus GO:0006406 mRNA export from nucleus GO:0006479 protein methylation GO:0006913 nucleocytoplasmic transport GO:0007498 mesoderm development GO:0007507 heart development GO:0008213 protein alkylation GO:0010452 histone H3-K36 methylation GO:0010793 regulation of mRNA export from nucleus GO:0014020 primary neural tube formation GO:0015931 nucleobase-containing compound transport GO:0016331 morphogenesis of embryonic epithelium GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018023 peptidyl-lysine trimethylation GO:0018027 peptidyl-lysine dimethylation GO:0018205 peptidyl-lysine modification GO:0021915 neural tube development GO:0030900 forebrain development GO:0032239 regulation of nucleobase-containing compound transport GO:0032259 methylation GO:0032386 regulation of intracellular transport GO:0034728 nucleosome organization GO:0034968 histone lysine methylation GO:0035148 tube formation GO:0035239 tube morphogenesis GO:0035441 cell migration involved in vasculogenesis GO:0043414 macromolecule methylation GO:0046822 regulation of nucleocytoplasmic transport GO:0046831 regulation of RNA export from nucleus GO:0048332 mesoderm morphogenesis GO:0048514 blood vessel morphogenesis GO:0048562 embryonic organ morphogenesis GO:0048568 embryonic organ development GO:0048608 reproductive structure development GO:0048701 embryonic cranial skeleton morphogenesis GO:0048704 embryonic skeletal system morphogenesis GO:0048705 skeletal system morphogenesis GO:0048706 embryonic skeletal system development GO:0048863 stem cell differentiation GO:0048864 stem cell development GO:0050657 nucleic acid transport GO:0050658 RNA transport GO:0051028 mRNA transport GO:0051168 nuclear export GO:0051169 nuclear transport GO:0051236 establishment of RNA localization GO:0060039 pericardium development GO:0060562 epithelial tube morphogenesis GO:0060606 tube closure GO:0060669 embryonic placenta morphogenesis GO:0060976 coronary vasculature development GO:0060977 coronary vasculature morphogenesis GO:0061458 reproductive system development GO:0071166 ribonucleoprotein complex localization GO:0071426 ribonucleoprotein complex export from nucleus GO:0071427 mRNA-containing ribonucleoprotein complex export from nucleus GO:0071824 protein-DNA complex subunit organization GO:0072175 epithelial tube formation GO:0097198 histone H3-K36 trimethylation GO:0097676 histone H3-K36 dimethylation GO:1904888 cranial skeletal system development GO:2000197 regulation of ribonucleoprotein complex localization
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:0046975 histone methyltransferase activity (H3-K36 specific)
Cellular Component	-

> 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	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SETD2 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	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
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

[ TOP ]

Statistical results of SETD2 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: 2.72; FDR: 0.000381	Sensitive 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	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
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

[ TOP ]

Points in the above scatter plot represent the expression difference of SETD2 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	-0.051	0.808
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.02	0.988
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.072	0.942
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.088	0.778
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.11	0.967
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.341	0.921
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.068	0.848
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.074	0.966
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.067	0.972
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.538	0.601
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	1.445	0.3
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.011	0.828

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SETD2 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	5.9	-5.9	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	7.1	-7.1	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	19	11.8	7.2	0.672
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	30.8	18.2	12.6	0.649
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
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	2.6	3.7	-1.1	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	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	36.4	38.5	-2.1	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	33.3	0	33.3	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	40	41.7	-1.7	1

Summary
Symbol	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SETD2. 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	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SETD2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SETD2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SETD2. 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	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SETD2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SETD2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SETD2
Name	SET domain containing 2
Aliases	HYPB; HIF-1; KIAA1732; FLJ23184; KMT3A; HBP231; HSPC069; SET2; p231HBP; huntingtin yeast partner B; huntingt ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SETD2 collected from DrugBank database.

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

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