TISIDB

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
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	PF00010 Helix-loop-helix DNA-binding domain
Function	Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0001503 ossification GO:0001649 osteoblast differentiation GO:0001655 urogenital system development GO:0001656 metanephros development GO:0001822 kidney development GO:0006260 DNA replication GO:0006275 regulation of DNA replication GO:0007507 heart development GO:0007517 muscle organ development GO:0007623 circadian rhythm GO:0030278 regulation of ossification GO:0030279 negative regulation of ossification GO:0030903 notochord development GO:0042476 odontogenesis GO:0042692 muscle cell differentiation GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0045445 myoblast differentiation GO:0045661 regulation of myoblast differentiation GO:0045662 negative regulation of myoblast differentiation GO:0045667 regulation of osteoblast differentiation GO:0045668 negative regulation of osteoblast differentiation GO:0048511 rhythmic process GO:0048568 embryonic organ development GO:0051052 regulation of DNA metabolic process GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051147 regulation of muscle cell differentiation GO:0051148 negative regulation of muscle cell differentiation GO:0070542 response to fatty acid GO:0071229 cellular response to acid chemical GO:0071396 cellular response to lipid GO:0071398 cellular response to fatty acid GO:0071407 cellular response to organic cyclic compound GO:0072001 renal system development GO:0072750 cellular response to leptomycin B GO:1901344 response to leptomycin B
Molecular Function	GO:0003714 transcription corepressor activity GO:0008134 transcription factor binding GO:0043177 organic acid binding GO:1901707 leptomycin B binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04350 TGF-beta signaling pathway hsa04550 Signaling pathways regulating pluripotency of stem cells
Reactome	-

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ID3 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 ID3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21191065	Lung Carcinoma	Inhibit immunity (T cell function)	We have shown that galectin-1 is highly expressed in lung cancer cell lines, together with the serum and surgical samples from lung cancer patients. Functionally, lung cancer-derived galectin-1 has been shown to alter the phenotypes of monocyte-derived DCs (MdDCs) and impair alloreactive T cell response, concomitant with the increase of CD4(+)CD25(+)FOXP3(+) regulatory T cells. The regulatory effect of galectin-1 is mediated, in part, through its ability to induce, in an Id3 (inhibitor of DNA binding 3)-dependent manner, the expression of IL-10 in monocytes and MdDCs. Of note, significant upregulation of IL-10 was seen in tumor-infiltrating CD11c(+) DCs in human lung cancer samples.

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
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 ID3 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	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
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 ID3 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	-1.214	0.0239
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.722	0.442
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.865	0.668
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.758	0.0897
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.683	0.708
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.852	0.709
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.208	0.694
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.261	0.834
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.131	0.925
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.81	0.721
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	1.414	0.671
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.114	0.439

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ID3 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	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	0	0	0	1
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	0	0	0	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	20	11.1	8.9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
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	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ID3. 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	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ID3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ID3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ID3. 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	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ID3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ID3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ID3
Name	inhibitor of DNA binding 3, dominant negative helix-loop-helix protein
Aliases	HEIR-1; bHLHb25; ID-like protein inhibitor HLH 1R21; class B basic helix-loop-helix protein 25; helix-loop-h ......
Chromosomal Location	1p36.13-p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ID3 collected from DrugBank database.

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

Browse ID3