Details for: CYP2C18

Gene ID: 1562

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CYP2C18

Ensembl ID: ENSG00000108242

Description: cytochrome P450 family 2 subfamily C member 18

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestinal epithelial cell CL0002563
    CSI 2.79
    rCSI 2.91%
    PRS 94.84
  • foveolar cell of stomach CL0002179
    CSI 2.71
    rCSI 5.77%
    PRS 96.81
  • periportal region hepatocyte CL0019026
    CSI 2.46
    rCSI 9.56%
    PRS 93.15
  • hepatocyte CL0000182
    CSI 2.32
    rCSI 4.15%
    PRS 94.67
  • enterocyte CL0000584
    CSI 2.24
    rCSI 3.61%
    PRS 93.77
  • colonocyte CL1000347
    CSI 1.87
    rCSI 2.68%
    PRS 94.76
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.56
    rCSI 8.67%
    PRS 96.47

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CYP2C18](/details-gene/1562) is a protein-coding gene located on chromosome 10q23.33 that encodes Cytochrome P450 2C18, a member of the cytochrome P450 superfamily of monooxygenases. These enzymes are central to the metabolism of a wide array of endogenous and exogenous compounds. Functionally, [CYP2C18](/details-gene/1562) is involved in several key metabolic processes, including the metabolism of xenobiotics, fatty acids such as linoleic acid, and retinoids ([Link](https://pubmed.ncbi.nlm.nih.gov/11093772/)). Consistent with this role, the gene shows prominent expression in tissues critical for detoxification and metabolism, with the highest significance observed in [intestinal epithelial cell](/details-cell/CL0002563)s and [hepatocyte](/details-cell/CL0000182)s. Variations in this gene family are associated with differences in drug metabolism ([601131](https://omim.org/entry/601131)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CYP2C18](/details-gene/1562) strongly indicates a specialized role in metabolic and detoxification processes concentrated in the liver and gastrointestinal tract. The gene's highest significance is observed in epithelial cell types that form the primary barrier and metabolic interface for ingested substances. These include [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 2.79), [foveolar cell of stomach](/details-cell/CL0002179) (CSI: 2.71), and various absorptive cells like [enterocyte](/details-cell/CL0000584)s (CSI: 2.24) and [colonocyte](/details-cell/CL1000347)s (CSI: 1.87). Furthermore, its high significance in liver cells, such as [periportal region hepatocyte](/details-cell/CL0019026) (CSI: 2.46) and [hepatocyte](/details-cell/CL0000182)s (CSI: 2.32), reinforces its function in systemic metabolism. The periportal region of the liver is particularly rich in enzymes for oxidative metabolism, which aligns with the known functions of P450 enzymes. This specific expression pattern suggests that [CYP2C18](/details-gene/1562) is a key enzymatic component responsible for the 'first-pass' metabolism of drugs and dietary compounds in both the gut wall and the liver. ## Pathways and Molecular Function The functions of [CYP2C18](/details-gene/1562) are centered on its enzymatic activity as an oxidoreductase, which is characteristic of cytochrome P450 proteins. Its protein product is localized primarily to the [endoplasmic reticulum membrane](/details-cell/GO:0005789), a major site of drug metabolism. The fundamental molecular functions include [monooxygenase activity](/details-cell/GO:0004497), [heme binding](/details-cell/GO:0020037), and [iron ion binding](/details-cell/GO:0005506), which are essential for its catalytic cycle. At a process level, [CYP2C18](/details-gene/1562) participates in the broad Reactome pathways of [Biological oxidations](/details-pathway/R-HSA-211859) and [Phase i - functionalization of compounds](/details-pathway/R-HSA-211945). More specifically, it is involved in the metabolism of endogenous signaling molecules, with annotated roles in the [linoleic acid metabolic process](/details-cell/GO:0043651) and the [retinoic acid metabolic process](/details-cell/GO:0042573). Its function as a [retinoic acid 4-hydroxylase](/details-cell/GO:0008401) is particularly notable, as it is involved in catabolizing all-trans-retinoic acid, a crucial regulator of cell differentiation and development ([Link](https://pubmed.ncbi.nlm.nih.gov/11093772/)). This specific enzymatic activity, combined with its high expression in epithelial tissues, suggests a role in maintaining local retinoid homeostasis within the gastrointestinal tract. ## Research Directions ### Proposed Hypotheses 1. Given its high expression in [intestinal epithelial cell](/details-cell/CL0002563)s and its function in the [xenobiotic metabolic process](/details-cell/GO:0006805), genetic polymorphisms in [CYP2C18](/details-gene/1562) may significantly alter the bioavailability and efficacy of orally administered drugs that are substrates for CYP2C enzymes, contributing to inter-individual differences in drug response. 2. The established role of [CYP2C18](/details-gene/1562) in the [retinoic acid metabolic process](/details-cell/GO:0042573) suggests that it modulates intestinal epithelial barrier integrity and immune cell differentiation by controlling local concentrations of retinoic acid, a key immunomodulatory molecule in the gut. Dysregulation of [CYP2C18](/details-gene/1562) could therefore be a contributing factor in inflammatory bowel diseases. ### Key Experiments To test the first hypothesis regarding the impact of [CYP2C18](/details-gene/1562) on first-pass drug metabolism, an experimental approach could involve using intestinal organoids derived from individuals with different known polymorphisms in the [CYP2C18](/details-gene/1562) gene. These organoids would be exposed to a known CYP2C substrate drug (e.g., ibuprofen or diclofenac). The concentrations of the parent drug and its hydroxylated metabolites in the culture medium could then be quantified over time using liquid chromatography-mass spectrometry (LC-MS). Comparing the metabolic rates across organoids with different genotypes would directly demonstrate the functional consequence of [CYP2C18](/details-gene/1562) variants on intestinal drug metabolism. ### Therapeutic Potential [CYP2C18](/details-gene/1562) itself is unlikely to be a direct therapeutic target for inhibition or activation, as its broad metabolic activity and high expression in critical organs like the liver and gut would likely lead to significant off-target effects and drug-drug interactions. However, its importance lies in the field of pharmacogenomics. Understanding an individual's [CYP2C18](/details-gene/1562) genotype could be crucial for personalizing drug therapy, particularly for drugs with a narrow therapeutic index that are metabolized by the CYP2C subfamily. Its main clinical relevance is therefore as a biomarker for predicting drug clearance, efficacy, and the risk of adverse reactions, rather than as a target for therapeutic intervention.

Genular Protein ID: 289754708

Symbol: CP2CI_HUMAN

Name: Cytochrome P450 2C18

UniProtKB Accession Codes:

P33260 B2R8K2 Q16703 Q16751 Q4VAT5 Q6GRG1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 17 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 29 EC 1 EMBL 17 Ensembl 2 EvolutionaryTrace 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 Rhea 8 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2009263

Title: Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily.

PubMed ID: 2009263

DOI: 10.1021/bi00227a012

PubMed ID: 8095407

Title:

PubMed ID: 8095407

DOI: 10.1021/bi00056a025

PubMed ID: 8333835

Title: Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18.

PubMed ID: 8333835

DOI: 10.1006/bbrc.1993.1803

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11093772

Title: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites.

PubMed ID: 11093772

DOI: 10.1124/mol.58.6.1341

PubMed ID: 16963442

Title: Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is the result of highly focused, peptide-dependent structural mimicry.

PubMed ID: 16963442

DOI: 10.1074/jbc.m606755200

Sequence Information:

  • Length: 490
  • Mass: 55711
  • Checksum: C933CF31F078FD1E
  • Sequence:
    • MDPAVALVLC LSCLFLLSLW RQSSGRGRLP SGPTPLPIIG NILQLDVKDM SKSLTNFSKV 
YGPVFTVYFG LKPIVVLHGY EAVKEALIDH GEEFSGRGSF PVAEKVNKGL GILFSNGKRW 
KEIRRFCLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTN ASPCDPTFIL GCAPCNVICS 
VIFHDRFDYK DQRFLNLMEK FNENLRILSS PWIQVCNNFP ALIDYLPGSH NKIAENFAYI 
KSYVLERIKE HQESLDMNSA RDFIDCFLIK MEQEKHNQQS EFTVESLIAT VTDMFGAGTE 
TTSTTLRYGL LLLLKYPEVT AKVQEEIECV VGRNRSPCMQ DRSHMPYTDA VVHEIQRYID 
LLPTNLPHAV TCDVKFKNYL IPKGTTIITS LTSVLHNDKE FPNPEMFDPG HFLDKSGNFK 
KSDYFMPFSA GKRMCMGEGL ARMELFLFLT TILQNFNLKS QVDPKDIDIT PIANAFGRVP 
PLYQLCFIPV

Genular Protein ID: 1824903753

Symbol: Q7Z348_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7Z348

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 3 DNASU 1 DisGeNET 1 EMBL 2 GO 7 Gene3D 1 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSR 1 PRINTS 2 PROSITE 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 RuleBase 1 SUPFAM 1

Sequence Information:

  • Length: 310
  • Mass: 35558
  • Checksum: C823EFD4AC53C732
  • Sequence:
    • EIRRFCLMTL RNFGMGKRSI EDRVQEEARC LVEELRKTNA SPCDPAFILG CAPCNVICSV 
IFHDRFDYKD QRFLNLMEKF NENLRILSSP WIQEKHNQQS EFTVESLIAT VTDMFGAGTE 
TTSTTLRYGL LLLLKYPEVT AKVQEEIECV VGRNRSPCMQ DRSHMPYTDA VVHEIQRYID 
LLPTNLPHAV TCDVKFKNYL IPKGTTIITS LTSVLHNDKE FPNPEMFDPG HFLDKSGNFK 
KSDYFMPFSA GKRMCMGEGL ARMELFLFLT TILQNFNLKS QVDPKDIDIT PIANAFGRVP 
PLYQLCFIPV