HS2ST1 Gene

HGNC Family	Sulfotransferases
Name	heparan sulfate 2-O-sulfotransferase 1
Description	Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Heparan sulfate 2‐O‐sulfotransferase 1 (HS2ST1) is a key enzyme in the biosynthesis of heparan sulfate (HS) that catalyzes the transfer of sulfate groups to the C2‐position of uronic acid residues. This modification is critical for generating specific sulfation patterns that dictate HS’s ability to interact with a wide range of ligands, including growth factors, morphogens, and guidance cues. HS2ST1 activity is essential for maintaining proper developmental signaling: for instance, loss of HS2ST1 in retinal ganglion cell axons leads to disorganized trajectories at the optic chiasm, indicating that 2‐O–sulfated HS is necessary for modulating responsiveness to repulsive cues such as Slit proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Additionally, in endothelial cells, inactivation of HS2ST1 disrupts the normal sulfation pattern of HS, resulting in compensatory increases in other sulfate groups that enhance binding of inflammatory mediators and alter leukocyte recruitment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the developing cerebral cortex, genetic ablation of HS2ST1 leads to a significant reduction in precursor proliferation, underscoring its role in modulating growth factor signaling such as that mediated by fibroblast growth factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Mutant mice lacking functional HS2ST1 produce HS chains devoid of 2‐O–sulfate groups yet show elevated levels of other sulfations; however, these compensatory changes fail to fully substitute for the discrete binding specificities provided by 2‐O sulfation. This imbalance is linked to developmental defects, including aberrant kidney formation and anomalies in neural and skeletal tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In human disease, bi-allelic pathogenic variants in HS2ST1 have been associated with a recognizable syndrome characterized by facial dysmorphism, developmental delay, corpus callosum anomalies, and renal agenesis. In patient-derived fibroblasts, diminished HS2ST1 expression results in HS with reduced 2‐O sulfation and subsequent blunting of fibroblast growth factor (FGF2)–induced MAPK signaling, emphasizing the enzyme’s importance in regulating extracellular signaling cascades that govern cellular proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, studies in breast cancer cell lines have demonstrated that modulation of HS2ST1 expression alters HS fine structure, influencing cell adhesion, mobility, and invasion. Overexpression of HS2ST1 was shown to inhibit invasion and reduce motility—effects that are mediated, at least in part, by altered binding of FGF-2 and changes in downstream MAPK signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Pratt, Christopher D Conway, Natasha M M-L Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulphation patterns generated by specific heparan sulfotransferase enzymes direct distinct aspects of retinal axon guidance at the optic chiasm."}]}, {"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.0505-06.2006"}], "href": "https://doi.org/10.1523/JNEUROSCI.0505-06.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16807321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16807321"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jakob Axelsson, Ding Xu, Bit Na Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-03-417139"}], "href": "https://doi.org/10.1182/blood-2012-03-417139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22791291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22791291"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David McLaughlin, Fredrik Karlsson, Natasha Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific modification of heparan sulphate is required for normal cerebral cortical development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Dev (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mod.2003.08.008"}], "href": "https://doi.org/10.1016/j.mod.2003.08.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14654220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14654220"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Valerie A Wilson, John T Gallagher, Catherine L R Merry "}, {"type": "b", "children": [{"type": "t", "text": "Heparan sulfate 2-O-sulfotransferase (Hs2st) and mouse development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycoconj J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/A:1025325222530"}], "href": "https://doi.org/10.1023/A:1025325222530"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12975615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12975615"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fu-Kai Zhang, Rui-Si Hu, Hany M Elsheikha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Global serum proteomic changes in water buffaloes infected with Fasciola gigantica."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parasit Vectors (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13071-019-3533-5"}], "href": "https://doi.org/10.1186/s13071-019-3533-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31159882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31159882"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Archana Vijaya Kumar, Stéphane Brézillon, Valérie Untereiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HS2ST1-dependent signaling pathways determine breast cancer cell viability, matrix interactions, and invasive behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.14539"}], "href": "https://doi.org/10.1111/cas.14539"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32573871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32573871"}]}]}]}
Synonyms	DJ604K5.2
Proteins	HS2ST_HUMAN
NCBI Gene ID	9653
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HS2ST1 has 8,990 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 121 datasets.

Click the + buttons to view associations for HS2ST1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 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 HS2ST1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HS2ST1 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 HS2ST1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HS2ST1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HS2ST1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HS2ST1 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 HS2ST1 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 HS2ST1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HS2ST1 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 HS2ST1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HS2ST1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HS2ST1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HS2ST1 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 HS2ST1 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 HS2ST1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HS2ST1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with HS2ST1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HS2ST1 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 HS2ST1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HS2ST1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HS2ST1 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 HS2ST1 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 HS2ST1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HS2ST1 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 HS2ST1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HS2ST1 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 HS2ST1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HS2ST1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HS2ST1 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 HS2ST1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with HS2ST1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.