ID4 Gene

HGNC Family	Basic helix-loop-helix proteins (BHLH)
Name	inhibitor of DNA binding 4, dominant negative helix-loop-helix protein
Description	This gene encodes a member of the inhibitor of DNA binding (ID) protein family. The encoded protein lacks DNA binding ability, and instead regulates gene expression through binding to and inhibiting basic helix-loop-helix transcription factors. This protein has been implicated in the regulation of diverse cellular processes that play a role in development and tumorigenesis. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ID4 is a member of the inhibitor of DNA‐binding (ID) protein family that plays multifaceted roles in both normal neural development and tumorigenesis. In the developing nervous system, ID4 is induced by bone morphogenetic protein signaling and functions by sequestering lineage‐determining basic helix–loop–helix transcription factors (such as OLIG1/2 and E2A) to inhibit oligodendrocyte commitment and promote astrogliogenesis. In this context, ID4 is also required for normal brain development by regulating the cell cycle (specifically the G1–S transition) of neural progenitors, thus controlling neural stem cell expansion and proper cortical growth (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the realm of cancer, ID4 exerts oncogenic functions by negatively regulating key tumor suppressors. In breast cancer, increased ID4 expression suppresses BRCA1 levels, thereby impairing DNA repair and contributing to tumor progression (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, its aberrant expression in astrocytes can drive transformation toward a stem-like state through the upregulation of cell cycle regulators and activation of Notch signaling, a mechanism implicated in glioblastoma development (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, gain-of-function mutant p53 induces ID4 expression via an E2F1-mediated mechanism, which in turn stabilizes pro-angiogenic mRNAs and enhances tumor neo-angiogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies reveal that ID4 functions as a critical regulator of cell fate by maintaining progenitor characteristics and modulating differentiation decisions in neural lineages, while its dysregulation contributes to oncogenic processes in multiple tissues.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jayshree Samanta, John A Kessler "}, {"type": "b", "children": [{"type": "t", "text": "Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01273"}], "href": "https://doi.org/10.1242/dev.01273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15280210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15280210"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyuson Yun, Akio Mantani, Sonia Garel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Id4 regulates neural progenitor proliferation and differentiation in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01430"}], "href": "https://doi.org/10.1242/dev.01430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15469968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15469968"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Solen Gokhan, Mireya Marin-Husstege, Shau Yu Yung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combinatorial profiles of oligodendrocyte-selective classes of transcriptional regulators differentially modulate myelin basic protein gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1850-05.2005"}], "href": "https://doi.org/10.1523/JNEUROSCI.1850-05.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16148239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16148239"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Piri L Welcsh, Ming K Lee, Rachel M Gonzalez-Hernandez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRCA1 transcriptionally regulates genes involved in breast tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.062181799"}], "href": "https://doi.org/10.1073/pnas.062181799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12032322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12032322"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Holger Heyn, Maria Engelmann, Sabine Schreek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA miR-335 is crucial for the BRCA1 regulatory cascade in breast cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.25962"}], "href": "https://doi.org/10.1002/ijc.25962"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21618216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21618216"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hye-Min Jeon, Xun Jin, Joong-Seob Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1668708"}], "href": "https://doi.org/10.1101/gad.1668708"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18676808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18676808"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Giulia Fontemaggi, Stefania Dell'Orso, Daniela Trisciuoglio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1669"}], "href": "https://doi.org/10.1038/nsmb.1669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19783986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19783986"}]}]}]}
Synonyms	BHLHB27, IDB4
Proteins	ID4_HUMAN
NCBI Gene ID	3400
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ID4 has 11,445 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for ID4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ID4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ID4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ID4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ID4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ID4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ID4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ID4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ID4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ID4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ID4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ID4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ID4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ID4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ID4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ID4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ID4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ID4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ID4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ID4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ID4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ID4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ID4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ID4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ID4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ID4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ID4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ID4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ID4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ID4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ID4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ID4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ID4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ID4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ID4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ID4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ID4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ID4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ID4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ID4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ID4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ID4 from the GeneSigDB Published Gene Signatures dataset.