COL6A3 Gene

HGNC Family	Collagens (COL)
Name	collagen, type VI, alpha 3
Description	This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COL6A3, which encodes the α3 chain of collagen VI, is an essential extracellular matrix (ECM) component with multifaceted functions in tissue homeostasis. In the musculoskeletal system, COL6A3 is critical for the assembly of collagen VI microfibrils that provide structural integrity; its disruption by mutations or aberrant splicing can impair ECM assembly and lead to a spectrum of myopathies—ranging from the milder Bethlem myopathy to the more severe Ullrich congenital muscular dystrophy, as well as atypical phenotypes such as isolated dystonia through dominant‐negative effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In adipose tissue, COL6A3 not only contributes to the organization of the ECM but also plays a role in modulating inflammation and tissue remodeling. Its mRNA levels correlate with body mass index and fat mass, and experimental models have shown that nutritional interventions, as well as factors such as leptin, regulate COL6A3 expression. Moreover, proteolytic cleavage of the α3 chain yields bioactive fragments (often termed endotrophin) that promote fibrosis, inflammation, and even tumor progression, thus linking altered COL6A3 activity to metabolic and neoplastic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In neoplastic settings, alternative splicing events involving COL6A3 have been identified in cancers of the colon, bladder, and prostate, suggesting that splice variants may encode proteins with altered functions that influence tumor behavior. In addition, gene fusion events—such as the fusion of COL6A3 with CSF1 observed in tenosynovial giant-cell tumors—highlight a tumor–landscaping role whereby aberrant COL6A3 regulatory elements drive overexpression of key growth factors, thereby modulating the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, COL6A3 functions as a multifunctional ECM protein; its proper expression and processing are vital for muscle and adipose tissue integrity, while its dysregulation via mutations, alternative splicing, or fusion events plays a significant role in the pathogenesis of muscular dystrophies, metabolic inflammation, and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert B West, Brian P Rubin, Melinda A Miller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0507321103"}], "href": "https://doi.org/10.1073/pnas.0507321103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16407111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16407111"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Naomi L Baker, Matthias Mörgelin, Rachel Peat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi025"}], "href": "https://doi.org/10.1093/hmg/ddi025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15563506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15563506"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ercan Demir, Patrizia Sabatelli, Valérie Allamand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/340608"}], "href": "https://doi.org/10.1086/340608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11992252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11992252"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "A K Lampe, Y Zou, D Sudano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20704"}], "href": "https://doi.org/10.1002/humu.20704"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18366090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18366090"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Michael Zech, Daniel D Lam, Ludmila Francescatto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2015.04.010"}], "href": "https://doi.org/10.1016/j.ajhg.2015.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26004199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26004199"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "T Aigner, L Hambach, S Söder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C5 domain of Col6A3 is cleaved off from the Col6 fibrils immediately after secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2001.6227"}], "href": "https://doi.org/10.1006/bbrc.2001.6227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11785962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11785962"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Magdalena Pasarica, Barbara Gowronska-Kozak, David Burk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipose tissue collagen VI in obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2009-0947"}], "href": "https://doi.org/10.1210/jc.2009-0947"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19837927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19837927"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kai Sun, Jiyoung Park, Olga T Gupta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms4485"}], "href": "https://doi.org/10.1038/ncomms4485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24647224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24647224"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura J McCulloch, Tom J Rawling, Kajsa Sjöholm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2014-1042"}], "href": "https://doi.org/10.1210/en.2014-1042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25337653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25337653"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Te-Cheng Pan, Rui-Zhu Zhang, Dessislava Markova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.433078"}], "href": "https://doi.org/10.1074/jbc.M112.433078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23564457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23564457"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kasper Thorsen, Karina D Sørensen, Anne Sofie Brems-Eskildsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M700590-MCP200"}], "href": "https://doi.org/10.1074/mcp.M700590-MCP200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18353764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18353764"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Emely Möller, Nils Mandahl, Fredrik Mertens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20501"}], "href": "https://doi.org/10.1002/gcc.20501"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17918257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17918257"}]}]}]}
Synonyms	DYT27, BTHLM1
Proteins	CO6A3_HUMAN
NCBI Gene ID	1293
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

COL6A3 has 10,683 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 125 datasets.

Click the + buttons to view associations for COL6A3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

COL6A3 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of COL6A3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 COL6A3 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 COL6A3 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 COL6A3 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 COL6A3 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 COL6A3 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 COL6A3 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 COL6A3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of COL6A3 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 COL6A3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with COL6A3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with COL6A3 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 COL6A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of COL6A3 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 COL6A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with COL6A3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with COL6A3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing COL6A3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of COL6A3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing COL6A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing COL6A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with COL6A3 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 COL6A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing COL6A3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of COL6A3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with COL6A3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with COL6A3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with COL6A3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with COL6A3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of COL6A3 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 COL6A3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving COL6A3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving COL6A3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with COL6A3 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 COL6A3 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 COL6A3 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 COL6A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with COL6A3 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 COL6A3 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 COL6A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.