NR1I3 (Nuclear Receptor Subfamily 1 Group I Member 3)
Key regulator of xenobiotic metabolism and drug clearance
Gene Information Card
| Symbol | NR1I3 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 1 Group I Member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 9970 ncbi.nlm.nih.gov/gene/9970 |
| Ensembl ID | ENSG00000143257 |
| UniProt ID | Q14994 |
| OMIM ID | 603881 |
| HGNC ID | 7969 |
| Aliases | CAR, MB67, CAR1 |
Description
NR1I3 encodes the constitutive androstane receptor (CAR), a nuclear receptor that regulates the expression of genes involved in xenobiotic and drug metabolism, including cytochrome P450 enzymes (e.g., CYP2B6, CYP3A4). CAR is primarily expressed in the liver and intestine and acts as a sensor of foreign chemicals, inducing detoxification pathways. It is also implicated in energy metabolism and liver homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Drug-induced liver injury | Activation of CAR by xenobiotics leads to induction of metabolizing enzymes, potentially causing hepatotoxicity | ClinVar; NCBI Gene |
| Hepatocellular carcinoma | Dysregulated CAR signaling may promote liver tumorigenesis through altered metabolism and proliferation | COSMIC; PubMed |
| Cholestasis | CAR activation modulates bile acid synthesis and transport, influencing cholestatic liver disease | OMIM; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 6.8 | Medium |
| Colon | 3.2 | Low |
| Kidney | 2.1 | Low |
| Adrenal gland | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 8.4 | Liver cancer cell line |
| Huh-7 | 7.9 | Hepatocellular carcinoma cell line |
| Caco-2 | 4.1 | Colorectal adenocarcinoma cell line |
| HEK293 | 1.2 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss of function; initiation codon change |
| c.100C>T (p.Arg34Trp) | missense | <0.01% | Altered ligand binding; reduced transactivation activity |
| c.403G>A (p.Glu135Lys) | missense | <0.01% | Impaired nuclear translocation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting the DNA-binding domain or ligand-binding pocket reduce transcriptional activity (e.g., p.Arg34Trp, p.Glu135Lys).
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in NR1I3.
Dominant Negative (DN)
Some variants may act as dominant-negative by forming inactive heterodimers with RXR, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • Zinc ion binding (GO:0008270) |
| • Ligand-activated transcription factor activity (GO:0038044) | • Regulation of transcription by RNA polymerase II (GO:0006357) |
| • Xenobiotic metabolic process (GO:0006805) | • Response to drug (GO:0042493) |
Pathways
• PXR/CAR-mediated xenobiotic metabolism (Reactome: R-HSA-211981)
• Cytochrome P450 induction by xenobiotics (KEGG: hsa00980)
• Nuclear receptor signaling (KEGG: hsa04080)
Protein Summary
The constitutive androstane receptor (CAR) is a 348-amino-acid nuclear receptor with a conserved N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It forms heterodimers with retinoid X receptor (RXR) and binds to response elements in target gene promoters. CAR is constitutively active but can be further activated by xenobiotics such as phenobarbital and inhibited by androstanol. It plays a central role in the adaptive response to chemical stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR1I3 Knockout HEK293 Cell Line | EDJ-KQ14492 | Human | 9970 | Details Get a Quote |
| NR1I3 Knockout Hep-G2 Cell Line | EDJ-KZ376 | Human | 9970 | Details Get a Quote |
| NR1I3 Knockout HeLa Cell Line | EDJ-KQ55289 | Human | 9970 | Details Get a Quote |
| NR1I3 Knockout A-549 Cell Line | EDJ-KQ63771 | Human | 9970 | Details Get a Quote |
| NR1I3 Knockout HCT 116 Cell Line | EDJ-KQ72230 | Human | 9970 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
