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Protein / target

Retinoic acid receptor alpha

Encoded byRARAP10276Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

MRNA regulatory element binding translation repressor

Strongest disease association

Neoplasms

Via encoding gene RARA · Genetic evidence · score 0.19

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 2020

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.

View complete UniProt function annotation

Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). 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:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758)

Subcellular location

NucleusCytoplasm
Domains and Gene Ontology detail (74)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytoplasm
  • Ccytosol
  • Cdendrite
  • Cnucleolus
  • Cnucleoplasm
  • Cnucleus
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cprotein-containing complex
  • CRNA polymerase II transcription regulator complex
  • Falpha-actinin binding

462 aa · 51 kDa · 3 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingGO · ReactomeCell proliferation & survivalGOTranscriptional regulationUniProt · GO · ReactomeImmune signallingUniProt · GO
View supporting evidence

Nuclear receptor signalling

  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway

Cell proliferation & survival

  • ·negative regulation of cell population proliferation
  • ·positive regulation of cell population proliferation

Transcriptional regulation

  • ·Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

Immune signalling

  • ·Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21…
  • ·positive regulation of interleukin-13 production
  • ·positive regulation of interleukin-4 production
  • ·positive regulation of interleukin-5 production
View underlying pathways (6)

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.

NCOR1NCOR2RXRAPMLZBTB16NCOA1RXRBNCOA2RARBRXRGRARA

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

2 medicines · 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.

Acne Vulgaris2 medicines
Hyperpigmentation1 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.

7 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

Isotretinoin
ApprovedAgonist

Retinoic acid receptor agonist

Indicated for Acne Vulgaris

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

Tretinoin
ApprovedAgonist

Retinoic acid receptor agonist

Indicated for Acne Vulgaris, Hyperpigmentation, Neoplasms

Acts on a complex — shared with RARB, RARG · 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 RARA

Gene-level evidence surfaced through the gene RARAthat 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.

Acute promyelocytic leukemia
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Acne Vulgaris
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Leukemia, Myeloid, Acute
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.51

Psoriasis
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Psoriasis vulgaris
0.71Moderately supported

Clinical evidence dominant · Open Targets 0.58

View evidence synthesis (5)
Acute promyelocytic leukemiaWell supported
0.76
agreement 0.600.91
Clinical83%Literature17%

Open Targets aggregate 0.61 · 2 independent evidence families

Acne VulgarisWell supported
0.75
agreement 0.590.91
Clinical99%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

Leukemia, Myeloid, AcuteModerately supported
0.74
agreement 0.620.86
Clinical49%Somatic mutation38%Literature13%

Open Targets aggregate 0.51 · 3 independent evidence families

PsoriasisModerately supported
0.73
agreement 0.570.89
Clinical99%Literature2%

Open Targets aggregate 0.59 · 2 independent evidence families

Psoriasis vulgarisModerately supported
0.71
agreement 0.560.86
Clinical100%Literature1%

Open Targets aggregate 0.58 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Acne Vulgaris0.61
Acute promyelocytic leukemia0.61
Psoriasis0.59
Psoriasis vulgaris0.58
Leukemia, Myeloid, Acute0.51
Neoplasms0.51
Sarcoma, Kaposi0.47

Drug development

11 compounds recorded · 7 approved · 4 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
TRETINOINApproval
ALITRETINOINApproval
NRX195183Phase 2
TAMIBAROTENEPhase 3
ETRETINATEApproval
ISOTRETINOINApproval
ADAPALENEApproval
ACITRETINApproval
TAZAROTENEApproval
MOFAROTENEPhase 1

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.

AntibodiesEmerging

Feasibility evidence (go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCastreceptor bindingToxCastNegative effects on testicular histology and spermatogenesisBrennan et al. (2024)

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)

RECRUITING · via Tretinoin · NCT06731140

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target 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. Label change2026-08-21

    Label change: ISOTRETINOIN (ANDA075945)

    fda · regulatory · fda · via Isotretinoin

  2. Label change2026-08-21

    Label change: ISOTRETINOIN (ANDA076135)

    fda · regulatory · fda · via Isotretinoin

  3. Label change2026-08-21

    Label change: ISOTRETINOIN (ANDA076356)

    fda · regulatory · fda · via Isotretinoin

  4. Regulatory approval2026-06-11

    Approval: TRETINOIN (ANDA214590)

    fda · regulatory · fda · via Tretinoin

  5. New publication2024-07-17
    Differentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration.

    In vitro cellular & developmental biology. Animal · 2024 · 20 citations · Europe PMC · via Tretinoin

  6. New publication2024-01-30
    Guidelines of care for the management of acne vulgaris.

    Journal of the American Academy of Dermatology · 2024 · 236 citations · Europe PMC · via Isotretinoin

  7. New publication2024-01-01
    Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis.

    JAMA dermatology · 2024 · 24 citations · Europe PMC · via Isotretinoin

  8. Safety communication2023-10-31

    Drug Safety Update: Isotretinoin (Roaccutane▼): introduction of new safety measures, including additional oversight of the initiation of treatment for patients under 18 years of age

    mhra · safety · mhra · via Isotretinoin

  9. Safety communication2023-04-26

    Drug Safety Update: Isotretinoin (Roaccutane▼): new safety measures to be introduced in the coming months, including additional oversight on initiation of treatment for patients under 18 years

    mhra · safety · mhra · via Isotretinoin

  10. Safety communication2017-10-26

    Drug Safety Update: Isotretinoin (Roaccutane): rare reports of erectile dysfunction and decreased libido

    mhra · safety · mhra · via Isotretinoin

  11. Safety communication2014-12-19

    Drug Safety Update: Isotretinoin (Roaccutane): reminder of possible risk of psychiatric disorders

    mhra · safety · mhra · via Isotretinoin

  12. New publication2010-09-01
    Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.

    The New England journal of medicine · 2010 · 1,349 citations · Europe PMC · via Isotretinoin

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

1 papers · to 2020

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

Most cited

Recent

Europe PMC papers linked directly to this protein.

Related family literature

2

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

The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.

Esposito M · The Journal of experimental medicine · 2024

via Receptors, Retinoic Acid

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

Tontonoz P · Genes & development · 1994

via Receptors, Retinoic Acid

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.