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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ARNT
aryl hydrocarbon receptor nuclear translocator
Chromosome 1 · 1q21.3
NCBI Gene: 405Ensembl: ENSG00000143437.22HGNC: HGNC:700UniProt: A8K6P0
317PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of glycolytic processDNA-binding transcription factor activity, RNA polymerase II-specificnuclear receptor activityaryl hydrocarbon receptor bindingneurodegenerative diseasecutaneous melanomaEndometrial Endometrioid AdenocarcinomaOvarian Endometrioid Adenocarcinoma with Squamous Differentiation
✦AI Summary

ARNT (aryl hydrocarbon receptor nuclear translocator) is a nuclear translocator protein that functions as an essential heterodimerization partner for the aryl hydrocarbon receptor (AHR). Upon AHR ligand binding, ARNT translocates to the nucleus where it forms a transcriptionally active AHR-ARNT complex 1. This heterodimer binds to xenobiotic response elements (XREs) and dioxin response elements (DREs) with core sequences 5'-TACGTG-3' and 5'-TGCGTG-3' respectively to regulate gene transcription 2. ARNT can also heterodimerize with HIF-1α to mediate hypoxic responses 3. The AHR-ARNT axis regulates diverse biological processes including drug metabolism, immune responses, and skin barrier function by upregulating genes like filaggrin and claudins 45. Beyond canonical signaling, ARNT participates in non-canonical pathways involving crosstalk with other transcription factors and signaling molecules 6. Clinically, ARNT dysfunction is associated with multiple malignancies, including glioblastoma where elevated ARNT correlates with poor prognosis and chemoresistance through p38-MAPK activation 7. AHR agonists activating ARNT, such as tapinarof and benvitimod, show therapeutic potential in inflammatory skin diseases like psoriasis and atopic dermatitis 45.

Sources cited
1
AHR-ARNT heterodimerization mechanism and ligand-dependent activation with structural details of DNA binding
PMID: 39900897
2
AHR-ARNT complex binds to XREs and dioxin response elements to regulate CYP1A1 expression
PMID: 21183436
3
ARNT (HIF-1β) is a PAS domain-containing protein that heterodimerizes with HIF-1α for hypoxic responses
PMID: 7539918
4
AHR/ARNT system regulates skin barrier functions, filaggrin expression, and immune responses; therapeutic agents like tapinarof target this pathway
PMID: 31683543
5
ARNT activation upregulates claudin expression and restores tight junction function in atopic dermatitis
PMID: 37734479
6
AHR participates in non-canonical signaling beyond canonical ARNT partnership, including crosstalk with other transcription factors
PMID: 36528068
7
ARNT is upregulated in glioblastoma, correlates with poor survival, and promotes chemoresistance through p38-MAPK signaling
PMID: 38806469
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.49Moderate
cutaneous melanomaOpen Targets
0.41Moderate
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
hemangioblastomaOpen Targets
0.37Weak
Hepatobiliary NeoplasmOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.35Weak
multiple sclerosisOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.35Weak
melanomaOpen Targets
0.32Weak
small cell lung carcinomaOpen Targets
0.30Weak
hepatocellular carcinomaOpen Targets
0.29Weak
multiple myelomaOpen Targets
0.28Weak
acute myeloid leukemiaOpen Targets
0.28Weak
esophageal squamous cell carcinomaOpen Targets
0.28Weak
oral squamous cell carcinomaOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AIPProtein interaction100%EPAS1Protein interaction100%CTNNB1Protein interaction100%CREB1Protein interaction100%NPAS4Protein interaction100%HSP90AB1Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Lung
86%
Liver
74%
Heart
64%
Brain
48%
Bone Marrow
43%
Gene Interaction Network
Click a node to explore
ARNTAIPEPAS1CTNNB1CREB1NPAS4HSP90AB1
PROTEIN STRUCTURE
Preparing viewer…
PDB3F1P · 1.17 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.21–0.39]
RankingsWhere ARNT stands among ~20K protein-coding genes
  • #1,059of 20,598
    Most Researched317 · top 10%
  • #1,879of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedARNT
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis.
PMID: 31683543
Int J Mol Sci · 2019
1.00
2
Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway.
PMID: 36528068
Biochem Pharmacol · 2023
0.90
3
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
PMID: 7539918
Proc Natl Acad Sci U S A · 1995
0.80
4
BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma.
PMID: 40595592
Nat Commun · 2025
0.76
5
Benvitimod Inhibits IL-4- and IL-13-Induced Tight Junction Impairment by Activating AHR/ARNT Pathway and Inhibiting STAT6 Phosphorylation in Human Keratinocytes.
PMID: 37734479
J Invest Dermatol · 2024
0.70