Protein / target

Aryl hydrocarbon receptor

AHRP35869Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
7
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Cis-regulatory region sequence-specific DNA binding

Primary system

Immune system

Strongest disease association

foveal hypoplasia 3

Genetic evidence · score 0.73

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

1 approved

7 linked trials

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

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.

Transcriptional regulationUniProt · GO · ReactomeImmune signallingGONuclear receptor signallingGOMetabolic enzyme activityGOApoptosis & cell deathGO
View supporting evidence

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

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity

Metabolic enzyme activity

  • ·xenobiotic metabolic process

Apoptosis & cell death

  • ·apoptotic process
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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

tapinarof
Narrow target profileApprovedAgonist

Aryl hydrocarbon receptor agonist

Appears in clinical studies involving atopic eczema, psoriasis vulgaris, psoriasis, psoriasis

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

foveal hypoplasia 30.73

Genetic · overall 0.45

retinitis pigmentosa 850.63

Genetic · overall 0.51

coffee consumption0.62

Genetic · overall 0.38

retinitis pigmentosa0.61

Genetic · overall 0.47

alcohol drinking0.53

Genetic · overall 0.33

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

psoriasis0.93

Clinical · overall 0.63

psoriasis vulgaris0.88

Clinical · overall 0.54

atopic eczema0.83

Clinical · overall 0.52

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neurodegenerative disease0.50

Pathway

leukemia0.38

Pathway

Show all associations
psoriasis0.63
psoriasis vulgaris0.54
atopic eczema0.52
retinitis pigmentosa 850.51
neurodegenerative disease0.50
retinitis pigmentosa0.47
foveal hypoplasia 30.45
leukemia0.38
coffee consumption0.38
alcohol drinking0.33

Open Targets ranks 3,204 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 1 total

TAPINAROFApproval

atopic eczema · psoriasis vulgaris · psoriasis

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Safety liabilities

Increase, Early Life Stage MortalityUroporphyriaAccumulation, Liver lipidregulation of transcription factor activityFormation, Hepatocellular and Bile duct tumorsN/A, Breast Cancer

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.

ClinicalTrials.gov via the drug-target graph.

Related literature

14

Papers indexed under “Receptors, Aryl Hydrocarbon” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.

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 literature, reached through a MeSH descriptor linked to this protein.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

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

atopic eczemaModerately 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

2

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  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.