CYP2S1: A Cytochrome P450 with Emerging Roles in Xenobiotic Metabolism and Cancer Biology
Explore the genomic context, expression patterns, and clinical significance of the CYP2S1 gene, a dioxin-inducible member of the cytochrome P450 superfamily.
Gene Information Card
| Symbol | CYP2S1 |
|---|---|
| Full Name | cytochrome P450 family 2 subfamily S member 1 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 29785 ncbi.nlm.nih.gov/gene/29785 |
| Ensembl ID | ENSG00000167601 |
| UniProt ID | Q96SQ9 |
| OMIM ID | 611064 |
| HGNC ID | 15665 |
| Aliases | CYP2S1, cytochrome P450 2S1 |
Description
CYP2S1 encodes a member of the cytochrome P450 superfamily of enzymes, which are heme-thiolate monooxygenases involved in the oxidative metabolism of both endogenous and exogenous compounds. CYP2S1 is primarily expressed in extrahepatic tissues, particularly epithelial cells of the respiratory and gastrointestinal tracts. Its expression is highly inducible by dioxins and other aryl hydrocarbon receptor (AhR) ligands. The enzyme is known to metabolize several xenobiotics, including some polycyclic aromatic hydrocarbons (PAHs) and retinoids. While its full range of physiological substrates is still under investigation, CYP2S1 is implicated in the metabolic activation of certain pro-carcinogens and the metabolism of all-trans retinoic acid, suggesting a role in both toxicology and cellular differentiation. The gene is also of interest in cancer biology due to its altered expression in various tumor types.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer | Altered expression of CYP2S1 has been observed in various cancers, including colorectal, breast, and lung cancers. It may influence tumor progression through its role in metabolizing signaling molecules like retinoids and arachidonic acid derivatives, potentially affecting cell proliferation and differentiation. | Expression studies (e.g., immunohistochemistry, RNA-seq) in tumor tissues show differential regulation compared to normal tissue. Functional studies are ongoing to determine its precise role in carcinogenesis. |
| Psoriasis | CYP2S1 expression is significantly upregulated in psoriatic skin lesions. It is hypothesized to contribute to the hyperproliferative state of keratinocytes by altering the local metabolism of retinoids and eicosanoids, which are crucial for skin homeostasis. | Gene expression profiling of skin biopsies from psoriasis patients shows consistent upregulation of CYP2S1 mRNA and protein compared to healthy controls. |
| Inflammatory Bowel Disease (IBD) | Similar to psoriasis, CYP2S1 expression is elevated in the inflamed intestinal epithelium of IBD patients. This may reflect a response to inflammatory mediators or altered retinoid metabolism within the gut mucosa. | Transcriptomic analyses of intestinal biopsies from ulcerative colitis and Crohn's disease patients demonstrate increased CYP2S1 expression in inflamed regions. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Trachea | 40.2 | High |
| Lung | 32.5 | High |
| Small Intestine | 28.1 | High |
| Colon | 22.4 | Medium |
| Stomach | 18.9 | Medium |
| Skin | 15.3 | Medium |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A-549 (Lung Carcinoma) | 45.6 | High expression, commonly used for studying CYP2S1 induction. |
| Caco-2 (Colorectal Adenocarcinoma) | 30.2 | Moderate to high expression, useful for intestinal metabolism studies. |
| HepG2 (Hepatocellular Carcinoma) | 2.1 | Low basal expression, but can be induced by AhR agonists. |
| MCF-7 (Breast Adenocarcinoma) | 12.8 | Variable expression, often studied in the context of hormone-dependent cancers. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3739912 | SNV (Intronic) | ~30% (Global) | No known functional effect; a common polymorphism. |
| rs3739913 | SNV (Intronic) | ~25% (Global) | No known functional effect; a common polymorphism. |
| c.1042C>T (p.Arg348Cys) | Missense | Rare | Located in the heme-binding region; predicted to be damaging, potentially affecting enzyme activity, but clinical significance is unconfirmed. |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants, such as p.Arg348Cys, are predicted to disrupt the heme-binding pocket or protein stability, potentially leading to reduced or absent enzymatic activity. However, no definitive loss-of-function variants have been functionally validated in large cohorts.
Gain of Function (GOF)
No gain-of-function mutations have been described for CYP2S1. Its expression is primarily regulated at the transcriptional level via the AhR pathway.
Dominant Negative (DN)
No evidence suggests that CYP2S1 mutations exert a dominant-negative effect. As a monomeric enzyme, a mutant allele is unlikely to interfere with the product of the wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • heme binding | • iron ion binding |
| • monooxygenase activity | • oxidoreductase activity |
| • acting on paired donors | • with incorporation or reduction of molecular oxygen |
| • retinoic acid 4-hydroxylase activity | • arachidonic acid epoxygenase activity |
| • integral component of membrane | • endoplasmic reticulum membrane |
| • xenobiotic metabolic process | • retinoic acid metabolic process |
Pathways
• Aryl hydrocarbon receptor (AhR) signaling pathway
• Retinoic acid metabolism
• Xenobiotics metabolism (Phase I)
Protein Summary
CYP2S1 is a 504-amino acid microsomal cytochrome P450 enzyme anchored to the endoplasmic reticulum membrane via its N-terminal hydrophobic domain. It contains a conserved cysteine residue that serves as the axial ligand for the heme iron, essential for its catalytic activity. The enzyme is known to catalyze the oxidative metabolism of various lipophilic substrates, including all-trans retinoic acid (to 4-hydroxy-retinoic acid) and certain polycyclic aromatic hydrocarbons. Its expression is strongly induced by ligands of the aryl hydrocarbon receptor (AhR), such as dioxins. The protein is thought to play a role in the metabolism of endogenous signaling molecules and the detoxification or activation of environmental procarcinogens. Structural studies are limited, but homology models based on other CYP2 family members suggest a typical P450 fold with a defined active site cavity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2S1 Knockout HEK293 Cell Line | EDJ-KQ2870 | Human | 29785 | Details Get a Quote |
| CYP2S1 Knockout A-549 Cell Line | EDJ-KQ23910 | Human | 29785 | Details Get a Quote |
| CYP2S1 Knockout HCT 116 Cell Line | EDJ-KQ23911 | Human | 29785 | Details Get a Quote |
| CYP2S1 Knockout HeLa Cell Line | EDJ-KQ23912 | Human | 29785 | Details Get a Quote |
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