EXT1 Gene

HGNC Family	Glycosyltransferases
Name	exostosin glycosyltransferase 1
Description	This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EXT1 encodes a key glycosyltransferase that, together with EXT2, catalyzes the elongation of heparan sulfate (HS) chains on proteoglycans, a process critical for proper cell–cell communication and extracellular matrix formation. The precise regulation of HS chain length and sulfation—which influences ligand binding—is dependent on balanced EXT1 activity; indeed, EXT1 not only functions as a co‐polymerase with EXT2 but also modulates HS structure through interactions with modifying enzymes such as NDST1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, EXT1‐dependent HS synthesis is critical for the binding and cellular uptake of misfolded proteins; for example, reduced EXT1 activity compromises HS‐mediated internalization of tau fibrils, implicating EXT1 in the prion‐like spread of neurodegenerative protein aggregates."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In skeletal tissues, loss‐of‐function mutations or haploinsufficiency of EXT1 perturb HS biosynthesis, thereby disrupting key developmental signals such as those mediated by fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), and Wnts. Such deficits are associated with hereditary multiple exostoses, where a “second hit” in EXT1 (or combined EXT1/EXT2 deficiencies) leads to cartilage‐capped bony outgrowths and altered chondrocyte differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, transcription factors such as Runx2 upregulate EXT1 expression in osteoprogenitors, thereby influencing osteogenic signaling pathways essential for proper bone formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n EXT1 also has important roles outside of development and differentiation. In virus–host interactions, for instance, the HS chains synthesized by EXT1 serve as attachment receptors required for efficient viral entry; deficiencies in EXT1 impair the infection of cells by pathogens such as herpes simplex virus and filoviruses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, genome‐wide association studies have implicated EXT1 in the regulation of human height"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and epigenetic inactivation of EXT1 in certain cancers highlights its putative tumor‐suppressor function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, EXT1 is central to HS biosynthesis and, by extension, to a wide array of signaling pathways that govern neurodegeneration, skeletal development, viral entry, and cell growth. Its proper function is essential for maintaining the structure and signaling competence of the extracellular matrix, while its loss or dysregulation leads to diverse pathologies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marta Busse, Almir Feta, Jenny Presto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703560200"}], "href": "https://doi.org/10.1074/jbc.M703560200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17761672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17761672"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jenny Presto, Maria Thuveson, Pernilla Carlsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression and heparan sulfate sulfation."}]}, {"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.0705807105"}], "href": "https://doi.org/10.1073/pnas.0705807105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18337501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18337501"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Brandon B Holmes, Sarah L DeVos, Najla Kfoury, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1301440110"}], "href": "https://doi.org/10.1073/pnas.1301440110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23898162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23898162"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "C Francannet, A Cohen-Tanugi, M Le Merrer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotype-phenotype correlation in hereditary multiple exostoses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.38.7.430"}], "href": "https://doi.org/10.1136/jmg.38.7.430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11432960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11432960"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kevin B Jones, Virginia Piombo, Charles Searby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0910875107"}], "href": "https://doi.org/10.1073/pnas.0910875107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080592"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Christianne M A Reijnders, Cathelijn J F Waaijer, Andrew Hamilton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "No haploinsufficiency but loss of heterozygosity for EXT in multiple osteochondromas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.100296"}], "href": "https://doi.org/10.2353/ajpath.2010.100296"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20813973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20813973"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Beverly M Zak, Manuela Schuksz, Eiki Koyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compound heterozygous loss of Ext1 and Ext2 is sufficient for formation of multiple exostoses in mouse ribs and long bones."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2011.02.001"}], "href": "https://doi.org/10.1016/j.bone.2011.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21310272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21310272"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nadiya M Teplyuk, Larisa M Haupt, Ling Ling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22108"}], "href": "https://doi.org/10.1002/jcb.22108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259985"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Toru Uyama, Miho Ishida, Tomomi Izumikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M609320200"}], "href": "https://doi.org/10.1074/jbc.M609320200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17040900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17040900"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Aileen O'Hearn, Minxiu Wang, Han Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of EXT1 and Glycosaminoglycans in the Early Stage of Filovirus Entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.03689-14"}], "href": "https://doi.org/10.1128/JVI.03689-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25741008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25741008"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Simon W Moore, Xian Zhang, Christopher D Lynch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Netrin-1 attracts axons through FAK-dependent mechanotransduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0999-12.2012"}], "href": "https://doi.org/10.1523/JNEUROSCI.0999-12.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22915102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22915102"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Santiago Ropero, Fernando Setien, Jesus Espada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh298"}], "href": "https://doi.org/10.1093/hmg/ddh298"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15385438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15385438"}]}]}]}
Synonyms	EXT, TTV, LGCR, TRPS2
Proteins	EXT1_HUMAN
NCBI Gene ID	2131
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EXT1 has 19,830 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 127 datasets.

Click the + buttons to view associations for EXT1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 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 EXT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with EXT1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EXT1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EXT1 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 EXT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EXT1 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 EXT1 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 EXT1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with EXT1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EXT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EXT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EXT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EXT1 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 EXT1 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 EXT1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EXT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EXT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EXT1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with EXT1 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 EXT1 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 EXT1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving EXT1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving EXT1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EXT1 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 EXT1 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 EXT1 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 EXT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EXT1 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 EXT1 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 EXT1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EXT1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.