IGFBP6 Gene

Name	insulin-like growth factor binding protein 6
Description	Enables identical protein binding activity and insulin-like growth factor II binding activity. Involved in cell migration and positive regulation of stress-activated MAPK cascade. Part of insulin-like growth factor binary complex. Implicated in obesity. Biomarker of breast cancer; in situ carcinoma; leiomyoma; and neovascular inflammatory vitreoretinopathy. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Insulin‐like growth factor binding protein–6 (IGFBP6) is emerging as a multifunctional regulator that not only modulates IGF signaling through its high–affinity binding to IGF–II but also exerts a variety of IGF–independent actions. Several studies have demonstrated that IGFBP6 is subject to proteolytic processing by matrix metalloproteinases; for example, MMP–2 and MMP–7 cleave IGFBP6, an event that can modify IGF bioavailability and thereby influence downstream signaling pathways involved in processes such as angiogenesis and tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the developing nervous system, proteolytic cleavage of IGFBP6 by MMP–9 and MMP–12 has been linked to the regulation of IGF–1 bioavailability during myelination, suggesting that normal myelinogenesis depends on the precise regulation of IGF activity by IGFBP6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, hypoxic conditions robustly induce IGFBP6 expression in vascular endothelial cells, where IGFBP6 acts in an IGF–independent manner to inhibit angiogenesis and counteract the pro–angiogenic effects of vascular endothelial growth factor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In parallel, observations in energy–deficit models show that circulating levels of IGFBP6 are reduced during acute caloric restriction, indicating that metabolic status may also regulate its expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to these extracellular functions, IGFBP6 can be actively imported into the nucleus via a specific nuclear localization signal. Nuclear IGFBP6 has been shown to promote apoptosis in cancer cells, revealing a non–canonical role that is distinct from its classical role in sequestering IGFs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, its gene transcription is modulated by TGF–β and β–catenin signaling pathways, further linking IGFBP6 to the regulation of tumor–stromal interactions and cellular proliferation in both normal and neoplastic tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that IGFBP6 serves as a critical node at the intersection of growth factor modulation, extracellular proteolysis, angiogenesis, metabolic adaptation, and cell fate regulation. Its diverse actions, which span from regulating IGF bioavailability through proteolytic cleavage to influencing nuclear apoptotic pathways, underscore its potential relevance as a therapeutic target in conditions ranging from developmental disorders and metabolic imbalances to cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard A Dean, Georgina S Butler, Yamina Hamma-Kourbali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00821-07"}], "href": "https://doi.org/10.1128/MCB.00821-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17908800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17908800"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michio Nakamura, Shin'ichi Miyamoto, Hiroyuki Maeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.06.010"}], "href": "https://doi.org/10.1016/j.bbrc.2005.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15964556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15964556"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peter H Larsen, Angelika Goncalves DaSilva, Katherine Conant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1880-05.2006"}], "href": "https://doi.org/10.1523/JNEUROSCI.1880-05.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16495447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16495447"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chunyang Zhang, Ling Lu, Yun Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGF binding protein-6 expression in vascular endothelial cells is induced by hypoxia and plays a negative role in tumor angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.26201"}], "href": "https://doi.org/10.1002/ijc.26201"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21618524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21618524"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jean L Chan, Catherine J Williams, Patricia Raciti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-0056"}], "href": "https://doi.org/10.1210/jc.2008-0056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18445667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18445667"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Cristiana Iosef, Theofanis Gkourasas, Christina Y H Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional nuclear localization signal in insulin-like growth factor binding protein-6 mediates its nuclear import."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2007-0959"}], "href": "https://doi.org/10.1210/en.2007-0959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18039785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18039785"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Saeid Amini Nik, Rasoul Pour Ebrahim, Kim Van Dam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGF-beta modulates beta-Catenin stability and signaling in mesenchymal proliferations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.05.024"}], "href": "https://doi.org/10.1016/j.yexcr.2007.05.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17601559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17601559"}]}]}]}
Synonyms	IBP6
Proteins	IBP6_HUMAN
NCBI Gene ID	3489
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IGFBP6 has 9,520 functional associations with biological entities spanning 8 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) extracted from 115 datasets.

Click the + buttons to view associations for IGFBP6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 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 IGFBP6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IGFBP6 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 IGFBP6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IGFBP6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IGFBP6 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 IGFBP6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IGFBP6 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 IGFBP6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IGFBP6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IGFBP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IGFBP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IGFBP6 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 IGFBP6 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 IGFBP6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IGFBP6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IGFBP6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IGFBP6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of IGFBP6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IGFBP6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with IGFBP6 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 IGFBP6 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 IGFBP6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IGFBP6 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 IGFBP6 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 IGFBP6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IGFBP6 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 IGFBP6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with IGFBP6 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with IGFBP6 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 IGFBP6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.