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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CYP4X1
cytochrome P450 family 4 subfamily X member 1
Chromosome 1 · 1p33|1
NCBI Gene: 260293Ensembl: ENSG00000186377.9HGNC: HGNC:20244UniProt: Q8N118
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
anandamide 14,15 epoxidase activityiron ion bindingoxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygenmonooxygenase activitycolorectal carcinomacolorectal cancerastrocytomaatypical teratoid rhabdoid tumor
✦AI Summary

CYP4X1 is a cytochrome P450 monooxygenase that selectively catalyzes epoxidation of anandamide's arachidonoyl moiety, modulating endocannabinoid signaling through insertion of molecular oxygen with electrons provided by NADPH via cytochrome P450 reductase 1. The enzyme is predominantly expressed in trachea, aorta, and brain, where it constitutes approximately 10 ng/mg microsomal protein in neurons, choroid epithelial cells, and vascular endothelial cells 2. CYP4X1 expression is regulated by PPARα activation 1 and shows female-biased hepatic expression 3. Mechanistically, CYP4X1/sEH-dependent endocannabinoid metabolism produces 14,15-EET-EA, which upregulates PD-L1, CXCL12, and TGF-β in cancer-associated fibroblasts via GPR119 signaling, promoting immune evasion in colorectal cancer 4. In immune checkpoint inhibitor toxicity, the butyrate-PPARα-CYP4X1 axis downregulation drives M1 macrophage polarization and proinflammatory factor production 5. Clinically, CYP4X1 overexpression correlates with advanced TNM stage, lymph node metastasis, and shorter survival in colorectal cancer patients 6. Additionally, CYP4X1 polymorphisms modulate disease onset in genetic and sporadic Creutzfeldt-Jakob disease 7.

Sources cited
1
CYP4X1 tissue distribution (trachea, aorta), PPARα-mediated transcriptional regulation, and catalytic function
PMID: 15797250
2
CYP4X1 is a major brain P450 protein with neuronal, choroid epithelial, and vascular endothelial localization
PMID: 16478468
3
Female-biased hepatic expression of CYP4X1 in humans
PMID: 28153492
4
CYP4X1/sEH-dependent 14,15-EET-EA production drives immune evasion via CAF-mediated PD-L1, CXCL12, TGF-β upregulation
PMID: 41276938
5
Butyrate-PPARα-CYP4X1 axis downregulation promotes M1 macrophage polarization and proinflammatory cytokine production in immune checkpoint inhibitor cardiotoxicity
PMID: 34980222
6
CYP4X1 overexpression associates with advanced TNM stage, metastasis, and poor prognosis in colorectal cancer
PMID: 40076494
7
CYP4X1 polymorphisms modulate disease onset in E200K genetic and sporadic Creutzfeldt-Jakob disease
PMID: 30032116
Disease Associationsⓘ20
colorectal carcinomaOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.04Suggestive
astrocytomaOpen Targets
0.04Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
central nervous system cancerOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
ependymomaOpen Targets
0.03Suggestive
obesityOpen Targets
0.03Suggestive
inherited obesityOpen Targets
0.03Suggestive
childhood supratentorial ependymomaOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
esophageal squamous cell carcinomaOpen Targets
0.02Suggestive
medulloblastomaOpen Targets
0.02Suggestive
oligodendrogliomaOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
large cell medulloblastomaOpen Targets
0.02Suggestive
hypopituitarismOpen Targets
0.02Suggestive
lung carcinomaOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PORProtein interaction91%NDOR1Protein interaction90%CYP4Z1Protein interaction79%MTRRProtein interaction71%
Tissue Expression6 tissues
Heart
100%
Lung
70%
Liver
56%
Brain
43%
Ovary
11%
Bone Marrow
7%
Gene Interaction Network
Click a node to explore
CYP4X1PORNDOR1CYP4Z1MTRR
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8N118
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.55–0.91]
RankingsWhere CYP4X1 stands among ~20K protein-coding genes
  • #14,677of 20,598
    Most Researched18
  • #8,267of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedCYP4X1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages.
PMID: 34980222
J Exp Clin Cancer Res · 2022
1.00
2
Conditional regulation of the human CYP4X1 and CYP4Z1 genes.
PMID: 15797250
Arch Biochem Biophys · 2005
0.90
3
CYP4X1/sEH-Dependent Endocannabinoid Metabolism Drives Fibroblast-Mediated Immunosuppression to Limit Immunotherapy in Colon Cancer.
PMID: 41276938
Adv Sci (Weinh) · 2026
0.80
4
Characterization of orphan human cytochromes P450.
PMID: 17786643
Drug Metab Rev · 2007
0.70
5
Age at onset of genetic (E200K) and sporadic Creutzfeldt-Jakob diseases is modulated by the
PMID: 30032116
J Neurol Neurosurg Psychiatry · 2018
0.60