BMP6 Gene

HGNC Family	Endogenous ligands, Bone morphogenetic proteins (BMP)
Name	bone morphogenetic protein 6
Description	This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Bone morphogenetic protein 6 (BMP6) is emerging as a multifunctional signaling molecule with diverse roles in systemic iron regulation, skeletal remodeling, cartilage formation, and even neural and synovial cell biology. In the liver, BMP6 is uniquely regulated by body iron levels and is essential for maintaining systemic iron homeostasis by inducing hepcidin expression via the BMP/SMAD pathway. Loss of BMP6 results in dramatic hepatic iron overload and impaired Smad activation, underscoring its nonredundant and critical role in iron sensing and regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, BMP6 contributes significantly to bone remodeling. It is secreted by osteoclasts and has been implicated as a coupling factor that recruits osteoprogenitors and promotes osteoblast differentiation, thereby facilitating the coordinated processes of bone resorption and formation. BMP6 signals through distinct type I and type II receptor complexes—often in conjunction with other BMPs—to induce osteoblastic and chondrogenic differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, BMP6 can enhance chondrogenesis in mesenchymal stem cell populations—for instance, supplementation with BMP6 can overcome deficits in adipose‐derived stem cells by upregulating receptor expression and restoring their chondrogenic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, aberrantly elevated BMP6 levels have been associated with pathological contexts. In Alzheimer’s disease, increased BMP6 expression in the hippocampus is correlated with diminished neurogenesis, suggesting that excessive BMP6 signaling may contribute to neural regenerative deficits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Similarly, within inflamed arthritic synovium, BMP6 appears to play a protective role by safeguarding fibroblast‐like synoviocytes against nitric oxide–induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings illustrate that BMP6 functions as a pivotal regulator in several physiological and pathophysiological processes—ranging from iron metabolism and bone/cartilage regeneration to neural and synovial cell survival—highlighting its potential as a therapeutic target in diseases such as hemochromatosis, osteoporosis, osteoarthritis, and neurodegeneration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Delphine Meynard, Léon Kautz, Valérie Darnaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of the bone morphogenetic protein BMP6 induces massive iron overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.320"}], "href": "https://doi.org/10.1038/ng.320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19252488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19252488"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "João Arezes, Niall Foy, Kirsty McHugh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Erythroferrone inhibits the induction of hepcidin by BMP6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2018-06-857995"}], "href": "https://doi.org/10.1182/blood-2018-06-857995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30097509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30097509"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yin Xia, Jodie L Babitt, Yisrael Sidis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-09-111567"}], "href": "https://doi.org/10.1182/blood-2007-09-111567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18326817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18326817"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Susanna Canali, Kimberly B Zumbrennen-Bullough, Amanda B Core, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial cells produce bone morphogenetic protein 6 required for iron homeostasis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2016-06-721571"}], "href": "https://doi.org/10.1182/blood-2016-06-721571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27864295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27864295"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Larry Pederson, Ming Ruan, Jennifer J Westendorf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0805133106"}], "href": "https://doi.org/10.1073/pnas.0805133106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19075223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19075223"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Karen Lavery, Pamela Swain, Dean Falb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800850200"}], "href": "https://doi.org/10.1074/jbc.M800850200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18436533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18436533"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yusuke Shiozawa, Younghun Jung, Anne M Ziegler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Erythropoietin couples hematopoiesis with bone formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0010853"}], "href": "https://doi.org/10.1371/journal.pone.0010853"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20523730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20523730"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "David G Winkler, May S Kung Sutherland, Ethan Ojala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M400524200"}], "href": "https://doi.org/10.1074/jbc.M400524200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545262"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Thea Hennig, Helga Lorenz, Angela Thiel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.20977"}], "href": "https://doi.org/10.1002/jcp.20977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17238135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17238135"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Leslie Crews, Anthony Adame, Christina Patrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1305-10.2010"}], "href": "https://doi.org/10.1523/JNEUROSCI.1305-10.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20844121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20844121"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Rik J U Lories, Inge Derese, Jan L Ceuppens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proinflammatory cytokines and differentially modulate fibroblast-like synoviocyte apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.11389"}], "href": "https://doi.org/10.1002/art.11389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14558086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14558086"}]}]}]}
Synonyms	VGR, VGR1
Proteins	BMP6_HUMAN
NCBI Gene ID	654
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BMP6 has 9,740 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 128 datasets.

Click the + buttons to view associations for BMP6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 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 BMP6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BMP6 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 BMP6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BMP6 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 BMP6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BMP6 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 BMP6 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 BMP6 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 BMP6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BMP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BMP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BMP6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing BMP6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BMP6 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 BMP6 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 BMP6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BMP6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BMP6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BMP6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with BMP6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BMP6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with BMP6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with BMP6 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 BMP6 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 BMP6 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 BMP6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BMP6 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 BMP6 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 BMP6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BMP6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.