CYP2S1 Gene

HGNC Family	Cytochrome P450s (CYP)
Name	cytochrome P450, family 2, subfamily S, polypeptide 1
Description	This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytochrome P450 2S1 (CYP2S1) is an atypical “orphan” enzyme predominantly expressed in extra‐hepatic tissues such as epithelial cells, keratinocytes, macrophages, and even brain microvessels. Its expression is highly inducible by environmental and physiological stresses – for example, by dioxin exposure via the aryl hydrocarbon receptor and by hypoxia through HIF‐1, as demonstrated in epithelial and lung cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and in liver cancer models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Functionally, CYP2S1 has emerged as a versatile catalyst involved in both xenobiotic and endogenous metabolism. In several studies, the enzyme utilizes peroxide-dependent mechanisms (often independent of NADPH) to oxidize and reduce its substrates. It participates in the oxidative bioactivation or detoxication of environmental carcinogens – for instance, converting benzo[a]pyrene dihydrodiol into potent epoxides"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and reducing N-hydroxylated derivatives of aromatic amines"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "– which underscores its potential role in chemical carcinogenesis."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, CYP2S1 modulates the metabolism of endogenous lipid mediators. In macrophages and bronchial epithelial cells, it transforms cyclooxygenase-derived prostaglandin precursors (PGG2 and PGH2) into bioactive lipids such as 12(S)-hydroxyheptadecatrienoic acid (12-HHT), thereby affecting prostaglandin E2 levels, cell proliferation, and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Complementary investigations in keratinocytes revealed that CYP2S1 contributes to retinoic acid metabolism, producing a metabolite profile similar to that seen with recombinant enzyme expression systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, knockdown of CYP2S1 in colorectal cancer models increased intrinsic prostaglandin E2 levels that in turn activated β-catenin signaling and cell proliferation, suggesting a tumor-suppressive function under certain conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional metabolomic studies with recombinant CYP2S1 have uncovered its ability to generate oxygenated derivatives of arachidonic acid and related fatty acids"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while other work demonstrated that fatty acid hydroperoxides can serve as physiological oxidants to support its catalytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings indicate that CYP2S1 acts as a key mediator at the crossroads of xenobiotic detoxication/bioactivation and the regulation of endogenous lipid signaling pathways, thereby influencing cell proliferation, inflammation, and cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Steven P Rivera, Feng Wang, Sirkku T Saarikoski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia."}]}, {"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.M609617200"}], "href": "https://doi.org/10.1074/jbc.M609617200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17277313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17277313"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alfredo Cabrera-Cano, Víctor Manuel Dávila-Borja, Sergio Juárez-Méndez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Funct (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbf.3612"}], "href": "https://doi.org/10.1002/cbf.3612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33377261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33377261"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peter H Bui, Oliver Hankinson "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of human cytochrome P450 2S1 using a synthetic gene-expressed protein in Escherichia coli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.109.057752"}], "href": "https://doi.org/10.1124/mol.109.057752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19713358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19713358"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kai Wang, F Peter Guengerich "}, {"type": "b", "children": [{"type": "t", "text": "Reduction of aromatic and heterocyclic aromatic N-hydroxylamines by human cytochrome P450 2S1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chem Res Toxicol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/tx400139p"}], "href": "https://doi.org/10.1021/tx400139p"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23682735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23682735"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Timo Frömel, Karin Kohlstedt, Rüdiger Popp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochrome P4502S1: a novel monocyte/macrophage fatty acid epoxygenase in human atherosclerotic plaques."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Basic Res Cardiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00395-012-0319-8"}], "href": "https://doi.org/10.1007/s00395-012-0319-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23224081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23224081"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "T W Madanayake, T P Fidler, T M Fresquez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochrome P450 2S1 depletion enhances cell proliferation and migration in bronchial epithelial cells, in part, through modulation of prostaglandin E(2) synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.112.046466"}], "href": "https://doi.org/10.1124/dmd.112.046466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22863683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22863683"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alison D McNeilly, Julie A Woods, Sally H Ibbotson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a human keratinocyte HaCaT cell line model to study the regulation of CYP2S1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.111.042085"}], "href": "https://doi.org/10.1124/dmd.111.042085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22039172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22039172"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chao Yang, Changyuan Li, Minle Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2014.12.008"}], "href": "https://doi.org/10.1016/j.yexcr.2014.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25557876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25557876"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mostafa I Fekry, Yi Xiao, Jeannette Zinggeler Berg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Role for the Orphan Human Cytochrome P450 2S1 in Polyunsaturated Fatty Acid "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ω"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-1 Hydroxylation Using an Untargeted Metabolomic Approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.119.089086"}], "href": "https://doi.org/10.1124/dmd.119.089086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31511258"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31511258"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Peter Bui, Satoshi Imaizumi, Sudheer Reddy Beedanagari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.110.035121"}], "href": "https://doi.org/10.1124/dmd.110.035121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21068195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21068195"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Clinton R Nishida, Melody Lee, Paul R Ortiz de Montellano "}, {"type": "b", "children": [{"type": "t", "text": "Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.110.065045"}], "href": "https://doi.org/10.1124/mol.110.065045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20566689"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20566689"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Marianna Stamou, Xianai Wu, Izabela Kania-Korwel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.113.054239"}], "href": "https://doi.org/10.1124/dmd.113.054239"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24255117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24255117"}]}]}]}
Synonyms	CYPIIS1
Proteins	CP2S1_HUMAN
NCBI Gene ID	29785
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CYP2S1 has 4,792 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 112 datasets.

Click the + buttons to view associations for CYP2S1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CYP2S1 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CYP2S1 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 CYP2S1 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 CYP2S1 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 CYP2S1 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 CYP2S1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CYP2S1 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 CYP2S1 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 CYP2S1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CYP2S1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CYP2S1 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 CYP2S1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CYP2S1 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 CYP2S1 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 CYP2S1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CYP2S1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CYP2S1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CYP2S1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CYP2S1 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 CYP2S1 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 CYP2S1 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 CYP2S1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CYP2S1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CYP2S1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CYP2S1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CYP2S1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CYP2S1 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 CYP2S1 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 CYP2S1 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 CYP2S1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CYP2S1 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 CYP2S1 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 CYP2S1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CYP2S1 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 CYP2S1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CYP2S1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CYP2S1 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 CYP2S1 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 CYP2S1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CYP2S1 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 CYP2S1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.