TISIDB

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
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	-
Domain	PF12851 Oxygenase domain of the 2OGFeDO superfamily
Function	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.

> Gene Ontology [ TOP ]
Biological Process	GO:0001655 urogenital system development GO:0001822 kidney development GO:0001889 liver development GO:0002244 hematopoietic progenitor cell differentiation GO:0002318 myeloid progenitor cell differentiation GO:0006206 pyrimidine nucleobase metabolic process GO:0006211 5-methylcytosine catabolic process GO:0006304 DNA modification GO:0006479 protein methylation GO:0006486 protein glycosylation GO:0006493 protein O-linked glycosylation GO:0008213 protein alkylation GO:0009100 glycoprotein metabolic process GO:0009101 glycoprotein biosynthetic process GO:0009112 nucleobase metabolic process GO:0009791 post-embryonic development GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018023 peptidyl-lysine trimethylation GO:0018205 peptidyl-lysine modification GO:0019857 5-methylcytosine metabolic process GO:0019858 cytosine metabolic process GO:0020027 hemoglobin metabolic process GO:0022612 gland morphogenesis GO:0030099 myeloid cell differentiation GO:0032259 methylation GO:0034968 histone lysine methylation GO:0035510 DNA dealkylation GO:0043413 macromolecule glycosylation GO:0043414 macromolecule methylation GO:0044270 cellular nitrogen compound catabolic process GO:0044728 DNA methylation or demethylation GO:0046700 heterocycle catabolic process GO:0048536 spleen development GO:0048732 gland development GO:0048872 homeostasis of number of cells GO:0051568 histone H3-K4 methylation GO:0061008 hepaticobiliary system development GO:0061484 hematopoietic stem cell homeostasis GO:0070085 glycosylation GO:0070988 demethylation GO:0070989 oxidative demethylation GO:0072001 renal system development GO:0072527 pyrimidine-containing compound metabolic process GO:0072529 pyrimidine-containing compound catabolic process GO:0072576 liver morphogenesis GO:0080111 DNA demethylation GO:0080182 histone H3-K4 trimethylation GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0005506 iron ion binding GO:0008198 ferrous iron binding GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors GO:0051213 dioxygenase activity GO:0070579 methylcytosine dioxygenase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-212165: Epigenetic regulation of gene expression R-HSA-74160: Gene Expression R-HSA-5221030: TET1,2,3 and TDG demethylate DNA

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TET2 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 TET2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29849141	Chronic Lymphocytic Leukemia	Resistant to immunotherapy	TET2-disrupted CAR T cells exhibited an epigenetic profile consistent with altered T cell differentiation and, at the peak of expansion, displayed a central memory phenotype. Experimental knockdown of TET2 recapitulated the potency-enhancing effect of TET2 dysfunction in this patient's CAR T cells.

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
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 TET2 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	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
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 TET2 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	-0.143	0.638
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.24	0.713
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.078	0.894
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.157	0.656
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.4	0.876
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.149	0.963
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.053	0.884
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.024	0.987
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.077	0.961
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.537	0.393
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	1.067	0.211
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.089	0.18

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TET2 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	11.1	2.7	8.4	0.12
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	11.1	3.4	7.7	0.176
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	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
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	0	0	1
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	2.6	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	18.2	0	18.2	0.199
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	20	0	20	0.294

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TET2. 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	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TET2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TET2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TET2. 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	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TET2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TET2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TET2
Name	tet methylcytosine dioxygenase 2
Aliases	FLJ20032; KIAA1546; tet oncogene family member 2; probable methylcytosine dioxygenase TET2; Methylcytosine d ......
Chromosomal Location	4q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TET2 collected from DrugBank database.

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

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