Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388).
Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143).
Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820).
Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820)
Homodimer (By similarity). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (PubMed:10395741, PubMed:28602820). Interacts with ARNT; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820, PubMed:34521881).
Binds MYBBP1A (By similarity). Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with the corepressor SMRT (PubMed:10395741). Interacts with NEDD8 and IVNS1ABP (PubMed:12215427, PubMed:16582008).
Interacts with BMAL1 (By similarity). Interacts with HSP90AB1 (By similarity). Interacts with TIPARP; leading to mono-ADP-ribosylation of AHR and subsequent inhibition of AHR (PubMed:23275542, PubMed:30373764)
Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle. Expressed in retinal photoreceptors (PubMed:29726989)
The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field.
As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP85 is an autosomal recessive form manifesting as early-onset progressive difficulty to adapt in dim light and gradually decreasing visual acuity in both eyes.
An autosomal recessive form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus.
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to AHR, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 19
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT01399593 | Antibody Mediated Rejection | Safety & Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization | PHASE2 | TERMINATED |
| NCT04200963 | Urothelial Carcinoma, Urothelial Carcinoma Bladder, Bladder Cancer, Bladder Disease, Solid Tumor, Solid Carcinoma, Solid Tumor, Adult, Metastatic Cancer, Advanced Solid Tumor, Advanced Cancer, Metastatic Bladder Cancer, Metastatic Urothelial Carcinoma, Locally Advanced Solid Tumor, Neoplasms, Neoplasm Metastasis, Neoplasm Malignant, Neoplasm, Bladder, Urothelial Neoplasm, Neoplasm, Urinary Bladder, Bladder Neoplasm, Bladder Urothelial Carcinoma | A Phase 1a/b Study of IK-175 as a Single Agent and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma | PHASE1 | COMPLETED |
| NCT05472506 | Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head Cancer, Neck Cancer, Head Cancer Neck, Neck Carcinoma | Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer | PHASE1 | WITHDRAWN |
| NCT01902420 | Acromegaly | Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations in Acromegaly | N/A | UNKNOWN |
| NCT04053387 | Plaque Psoriasis | Long Term Extension Study of Tapinarof for Plaque Psoriasis in Adults (3003) | PHASE3 | COMPLETED |
| NCT01549483 | Asthma, Airway Hyperresponsiveness | Small Airways Disease in Asymptomatic and Symptomatic Subjects With Airway Hyperresponsiveness (AHR) | N/A | COMPLETED |
| NCT06213688 | Psoriasis, Atopic Dermatitis | Involvement of Pollutants in Atopic Dermatitis and Psoriasis | NA | UNKNOWN |
| NCT05753254 | Reactive Hyperemia, Micro RNA, Heart Rate Variability, DNA Strand Breaks, Oxidative Stress, Heat Stress | Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Training | NA | COMPLETED |
| NCT00291382 | Asthma | Airway Hyper-responsiveness Study In Asthma Using Salmeterol/Fluticasone Propionate Combination Product | PHASE4 | COMPLETED |
| NCT01106027 | Kidney Transplant | Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant | PHASE1, PHASE2 | TERMINATED |