HS6ST2 Gene

HGNC Family	Sulfotransferases
Name	heparan sulfate 6-O-sulfotransferase 2
Description	Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HS6ST2 is a Golgi‐resident enzyme belonging to the heparan sulfate 6–O–sulfotransferase family that catalyzes the transfer of sulfate to the 6–O position of N–sulphoglucosamine residues in heparan sulfate (HS), thereby fine–tuning HS structure and its interactions with growth factors and receptors. Studies have shown that tissue–specific expression of HS6ST2 isoforms contributes to differences in HS sulfation patterns—for example, an “original” form predominates in brain while a shorter variant is expressed in ovary, placenta, and fetal kidney—suggesting a role for HS6ST2 in conferring region–specific HS functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Alterations in HS6ST2 activity modulate key signaling pathways, as reduced 6–O sulfation dampens fibroblast growth factor (FGF)–mediated responses and influences the assembly of HS-growth factor–receptor complexes, thereby affecting processes such as angiogenesis and cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In cancer, overexpression of HS6ST2 has been implicated in promoting Notch signaling, epithelial–mesenchymal transition, and invasiveness in pancreatic and thyroid carcinomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Conversely, in musculoskeletal tissues, down–regulation of HS6ST2—mediated in part by miR–23b–3p or other mechanisms—correlates with enhanced catabolic activity, matrix degradation, and compromised chondrocyte differentiation in osteoarthritis and Kashin–Beck disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, a deleterious mutation in HS6ST2 has been linked to X–linked intellectual disability with concomitant myopia, underlining its importance in neurodevelopment and visual system formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Additional roles for HS6ST2 emerge from studies in metabolic regulation, where its loss leads to altered thyroid hormone levels, reduced brown adipose tissue energy metabolism, and consequent features of metabolic syndrome"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in mast cell function, where proper 6–O sulfation is essential for the stable storage of key proteases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings highlight HS6ST2 as a central regulator of HS–dependent signal transduction across diverse biological contexts, with its altered expression or function contributing to a range of pathological conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroko Habuchi, Goichiro Miyake, Ken Nogami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biosynthesis of heparan sulphate with diverse structures and functions: two alternatively spliced forms of human heparan sulphate 6-O-sulphotransferase-2 having different expression patterns and properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021259"}], "href": "https://doi.org/10.1042/BJ20021259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12492399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12492399"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Noriko Sugaya, Hiroko Habuchi, Naoko Nagai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "6-O-sulfation of heparan sulfate differentially regulates various fibroblast growth factor-dependent signalings in culture."}]}, {"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.M705948200"}], "href": "https://doi.org/10.1074/jbc.M705948200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18281280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18281280"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cristina Ferreras, Graham Rushton, Claire L Cole, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial heparan sulfate 6-O-sulfation levels regulate angiogenic responses of endothelial cells to fibroblast growth factor 2 and vascular endothelial growth factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.384875"}], "href": "https://doi.org/10.1074/jbc.M112.384875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22927437"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22927437"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kai Song, Qin Li, Yong-Bo Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20110297"}], "href": "https://doi.org/10.1042/BJ20110297"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21443520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21443520"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Claire L Cole, Graham Rushton, Gordon C Jayson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ovarian cancer cell heparan sulfate 6-O-sulfotransferases regulate an angiogenic program induced by heparin-binding epidermal growth factor (EGF)-like growth factor/EGF receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.534263"}], "href": "https://doi.org/10.1074/jbc.M113.534263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24563483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24563483"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuanxu Guo, Zixin Min, Congshan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of HS6ST2 by miR-23b-3p enhances matrix degradation through p38 MAPK pathway in osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0729-0"}], "href": "https://doi.org/10.1038/s41419-018-0729-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29899528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29899528"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wei Wang, Xichi Ju, Zhengming Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2015.2272"}], "href": "https://doi.org/10.3892/ijmm.2015.2272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26133911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26133911"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wei Wang, Bo Zhong, Jian Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulated HS6ST2 in osteoarthritis and Kashin-Beck disease inhibits cell viability and influences expression of the genes relevant to aggrecan metabolism of human chondrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rheumatology (Oxford) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/rheumatology/ker230"}], "href": "https://doi.org/10.1093/rheumatology/ker230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21972422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21972422"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Leda Paganini, Loubna A Hadi, Massimiliano Chetta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13485"}], "href": "https://doi.org/10.1111/cge.13485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30471091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30471091"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Naoko Nagai, Hiroko Habuchi, Noriko Sugaya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of heparan sulfate 6-O-sulfation in the regulation of energy metabolism and the alteration of thyroid hormone levels in male mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwt037"}], "href": "https://doi.org/10.1093/glycob/cwt037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23690091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23690091"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Md Ferdous Anower-E-Khuda, Hiroko Habuchi, Naoko Nagai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulfate 6-O-sulfotransferase isoform-dependent regulatory effects of heparin on the activities of various proteases in mast cells and the biosynthesis of 6-O-sulfated heparin."}]}, {"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.M112.416651"}], "href": "https://doi.org/10.1074/jbc.M112.416651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23223449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23223449"}]}]}]}
Proteins	H6ST2_HUMAN
NCBI Gene ID	90161
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HS6ST2 has 3,929 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 109 datasets.

Click the + buttons to view associations for HS6ST2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HS6ST2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HS6ST2 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 HS6ST2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HS6ST2 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 HS6ST2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HS6ST2 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 HS6ST2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HS6ST2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HS6ST2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HS6ST2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HS6ST2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HS6ST2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HS6ST2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 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 HS6ST2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HS6ST2 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 HS6ST2 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 HS6ST2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HS6ST2 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 HS6ST2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HS6ST2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with HS6ST2 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 HS6ST2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of HS6ST2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of HS6ST2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.