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Protein / target

Retinoic acid receptor RXR-alpha

Encoded byRXRAP19793Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Strongest disease association

Psoriasis

Via encoding gene RXRA · Clinical evidence · score 0.59

Therapeutic position

Established drug target

Small molecules

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

Receptor for retinoic acid that acts as a transcription factor.

View complete UniProt function annotation

Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:37478846, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632)

Subcellular location

NucleusCytoplasmMitochondrion
Domains and Gene Ontology detail (50)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cmitochondrion
  • Cnucleoplasm
  • Cnucleus
  • Creceptor complex
  • CRNA polymerase II transcription regulator complex
  • FDNA binding domain binding
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fdouble-stranded DNA binding
  • Fenzyme binding

462 aa · 51 kDa · 2 isoforms

Biological roles

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

Lipid & lipoprotein metabolismUniProt · GONuclear receptor signallingUniProt · GOTranscriptional regulationUniProt · GO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:…
  • ·cellular response to low-density lipoprotein particle stimulus
  • ·positive regulation of cholesterol efflux
  • ·positive regulation of lipid metabolic process

Nuclear receptor signalling

  • ·Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:…
  • ·nuclear receptor activity

Transcriptional regulation

  • ·Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

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

Approved medicines with mapped indications

1 medicine · 3 areas

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.

Lymphoma, T-Cell1 medicine
Lymphoma, T-Cell, Cutaneous1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

5 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. 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.

bexarotene
ApprovedAgonist

Retinoid X receptor agonist

Indicated for Lymphoma, T-Cell, Lymphoma, T-Cell, Cutaneous, Neoplasms

Acts on a complex — shared with RXRB, RXRG · 1 of 3 recorded protein targets — narrow recorded profile

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 RXRA

Gene-level evidence surfaced through the gene RXRAthat 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
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.59

Lymphoma, T-Cell, Cutaneous
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

Psoriasis vulgaris
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.52

Carcinoma, Non-Small-Cell Lung
0.60Moderately supported

Clinical evidence dominant · Open Targets 0.42

Neoplasms
0.60Moderately supported

Clinical evidence dominant · Open Targets 0.48

View evidence synthesis (5)
PsoriasisModerately supported
0.72
agreement 0.570.88
Clinical97%Literature3%

Open Targets aggregate 0.59 · 2 independent evidence families

Lymphoma, T-Cell, CutaneousModerately supported
0.68
agreement 0.530.83
Clinical98%Literature2%

Open Targets aggregate 0.55 · 2 independent evidence families

Psoriasis vulgarisModerately supported
0.64
agreement 0.480.79
Clinical98%Literature2%

Open Targets aggregate 0.52 · 2 independent evidence families

Carcinoma, Non-Small-Cell LungModerately supported
0.60
agreement 0.480.72
Clinical57%Somatic mutation40%Literature3%

Open Targets aggregate 0.42 · 3 independent evidence families

NeoplasmsModerately supported
0.60
agreement 0.440.75
Clinical90%Literature11%

Open Targets aggregate 0.48 · 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
Psoriasis0.59
Lymphoma, T-Cell, Cutaneous0.55
Psoriasis vulgaris0.52
Urinary Bladder Neoplasms0.51
Sarcoma, Kaposi0.48
Neoplasms0.48
Carcinoma, Non-Small-Cell Lung0.42
Urinary bladder carcinoma0.39

Drug development

8 compounds recorded · 5 approved · 3 in clinical development

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 (8)
IRX-4204Phase 2
SDX-101Phase 2
BEXAROTENEApproval
ALITRETINOINApproval
DANTHRONApproval
MOFAROTENEPhase 1
ETRETINATEApproval
ACITRETINApproval

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 (uniprot ubiquitination 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 · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

anemiaClinPGxanemia and neutropeniaClinPGxregulation of transcription factor activityToxCastprotein stabilizationToxCast

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

30

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.

View all trials (26)

TERMINATED · via bexarotene · NCT00615784

UNKNOWN · via bexarotene · NCT00845351

COMPLETED · via bexarotene · NCT00316030

ClinicalTrials.gov via the drug-target graph.

What's happening now

1

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. Regulatory approval2001-03-29

    Approval: Targretin (EMA)

    ema · regulatory · ema · via bexarotene

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.

Related family literature

1

Papers about “Retinoid X Receptors” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.

Tontonoz P · Genes & development · 1994

via Retinoid X Receptors

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.