TISIDB

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
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	PF00010 Helix-loop-helix DNA-binding domain
Function	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'.

> Gene Ontology [ TOP ]
Biological Process	GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0010720 positive regulation of cell development GO:0045666 positive regulation of neuron differentiation GO:0050769 positive regulation of neurogenesis GO:0051962 positive regulation of nervous system development GO:0065004 protein-DNA complex assembly GO:0071824 protein-DNA complex subunit organization
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001011 transcription factor activity, sequence-specific DNA binding, RNA polymerase recruiting GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001083 transcription factor activity, RNA polymerase II basal transcription factor binding GO:0001085 RNA polymerase II transcription factor binding GO:0001087 transcription factor activity, TFIIB-class binding GO:0001091 RNA polymerase II basal transcription factor binding GO:0001093 TFIIB-class transcription factor binding GO:0001098 basal transcription machinery binding GO:0001099 basal RNA polymerase II transcription machinery binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor binding GO:0043425 bHLH transcription factor binding GO:0046982 protein heterodimerization activity GO:0070888 E-box binding
Cellular Component	GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0005667 transcription factor complex GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-375170: CDO in myogenesis R-HSA-1266738: Developmental Biology R-HSA-201722: Formation of the beta-catenin R-HSA-525793: Myogenesis R-HSA-162582: Signal Transduction R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TCF4 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 TCF4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25568183	Melanoma	Inhibit immunity (T cell function)	Hence, β-catenin/TCF4 signaling induces local regulatory DC and regulatory T-cell phenotypes via the RA pathway, identifying this pathway as an important target for anticancer immunotherapy.

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
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 TCF4 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	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
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 TCF4 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	-1.113	0.0482
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.435	0.327
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.889	0.49
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.024	0.952
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.095	0.969
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.065	0.984
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.545	0.295
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.522	0.754
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.597	0.743
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.033	0.434
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	2.154	0.258
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.159	0.219

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TCF4 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	7.4	5.5	1.9	0.66
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	6.8	0.6	1
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	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	7.4	0.5	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TCF4. 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	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TCF4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TCF4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TCF4. 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	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TCF4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TCF4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TCF4
Name	transcription factor 4
Aliases	SEF2-1B; ITF2; bHLHb19; E2-2; ITF-2; PTHS; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1D; SL3-3 enhancer factor 2; c ......
Chromosomal Location	18q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TCF4 collected from DrugBank database.

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

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