Back to discover

Protein / target

Aryl hydrocarbon receptor

Encoded byAHRP35869Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
7
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Cis-regulatory region sequence-specific DNA binding

Strongest disease association

Foveal hypoplasia 3

Via encoding gene AHR · Genetic evidence · score 0.73

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

14 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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 the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820)

Subcellular location

CytoplasmNucleus
Domains and Gene Ontology detail (50)

Domains & features

bHLHPAS 1PAS 2PAC

Gene Ontology

  • Caryl hydrocarbon receptor complex
  • Cchromatin
  • Ccytoplasm
  • Ccytosol
  • Ccytosolic aryl hydrocarbon receptor complex
  • Cnuclear aryl hydrocarbon receptor complex
  • Cnucleoplasm
  • Cnucleus
  • Cprotein-containing complex
  • Ctranscription regulator complex
  • Fcis-regulatory region sequence-specific DNA binding
  • FDNA binding

848 aa · 96 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Nuclear receptor signallingUniProt · GOCell migrationUniProtLipid & lipoprotein metabolismReactomeTranscriptional regulationUniProt · GO · ReactomeImmune signallingGO
View supporting evidence

Nuclear receptor signalling

  • ·Ligand-activated transcription factor that enables cells to adapt to changing conditions…
  • ·nuclear receptor activity

Cell migration

  • ·Ligand-activated transcription factor that enables cells to adapt to changing conditions…

Lipid & lipoprotein metabolism

  • ·Endogenous sterols

Transcriptional regulation

  • ·Ligand-activated transcription factor that enables cells to adapt to changing conditions…
  • ·transcription regulator complex
  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

Immune signalling

  • ·negative regulation of inflammatory response
  • ·negative regulation of T cell mediated immune response to tumor cell
  • ·regulation of adaptive immune response
  • ·regulation of B cell proliferation
View underlying pathways (5)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

AIPARNTHSP90A…HSP90A…CYP1A1ARNT2PTGES3ESR1ENSP00…CYP1A2AHR

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Psoriasis1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

tapinarof
Narrow target profileApprovedAgonist

Aryl hydrocarbon receptor agonist

Indicated for Psoriasis

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene AHR

Gene-level evidence surfaced through the gene AHRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Psoriasis
0.83Well supported

Clinical evidence dominant · Open Targets 0.63

Foveal hypoplasia 3
0.76Well supported

Genetic evidence dominant · Open Targets 0.45

Retinitis Pigmentosa
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.47

Psoriasis vulgaris
0.67Moderately supported

Clinical evidence dominant · Open Targets 0.54

Dermatitis, Atopic
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.52

View evidence synthesis (5)
PsoriasisWell supported
0.83
agreement 0.720.94
Clinical59%Genetic30%Literature11%

Open Targets aggregate 0.63 · 3 independent evidence families

Foveal hypoplasia 3Well supported
0.76
agreement 0.640.89
Genetic87%Animal model13%

Open Targets aggregate 0.45 · 2 independent evidence families

Retinitis PigmentosaModerately supported
0.68
agreement 0.560.80
Genetic78%Animal model21%Literature1%Genetic literaturedup

Open Targets aggregate 0.47 · 3 independent evidence families · 1 not counted as duplicate

Psoriasis vulgarisModerately supported
0.67
agreement 0.510.82
Clinical97%Literature3%

Open Targets aggregate 0.54 · 2 independent evidence families

Dermatitis, AtopicModerately supported
0.64
agreement 0.490.80
Clinical93%Literature7%

Open Targets aggregate 0.52 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Psoriasis0.63
Psoriasis vulgaris0.54
Dermatitis, Atopic0.52
Retinitis pigmentosa 850.51
Neurodegenerative Diseases0.50
Retinitis Pigmentosa0.47
Foveal hypoplasia 30.45
Leukemia0.38
Coffee consumption0.38
Alcohol drinking0.33

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)
TAPINAROFApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Increase, Early Life Stage MortalityAOP-WikiUroporphyriaAOP-WikiAccumulation, Liver lipidAOP-Wikiregulation of transcription factor activityToxCastFormation, Hepatocellular and Bile duct tumorsAOP-WikiN/A, Breast CancerAOP-Wiki

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

7

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

NOT_YET_RECRUITING · via tapinarof · NCT07352566

ENROLLING_BY_INVITATION · via tapinarof · NCT05981118

ENROLLING_BY_INVITATION · via tapinarof · NCT06661213

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2021-12-01
    Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis.

    The New England journal of medicine · 2021 · 141 citations · Europe PMC · via tapinarof

  2. New publication2020-07-29
    Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis.

    International journal of molecular sciences · 2020 · 259 citations · Europe PMC · via tapinarof

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

14 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Tanaka T · Cold Spring Harbor perspectives in biology · 2014

Roager HM · Nature communications · 2018

Ankley GT · Environmental toxicology and chemistry · 2010

Scott SA · Proceedings of the National Academy of Sciences of the United States of America · 2020

Recent

The influence of AHR on immune and tissue biology.

Stockinger B · EMBO molecular medicine · 2024

Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor.

Scott SA · Proceedings of the National Academy of Sciences of the United States of America · 2020

Europe PMC papers linked directly to this protein.