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Protein / target

Estrogen-related receptor gamma

Encoded byESRRGP62508Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
1
Clinical candidates
5
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Strongest disease association

Movement Disorders

Via encoding gene ESRRG · Genetic evidence · score 0.77

Therapeutic position

Clinically advancing 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

Orphan receptor that acts as a transcription activator in the absence of bound ligand.

View complete UniProt function annotation

Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle

Subcellular location

Nucleus
Domains and Gene Ontology detail (20)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Cnucleoplasm
  • Cnucleus
  • FAF-2 domain binding
  • FDNA-binding transcription activator activity, RNA polymerase II-specific
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Festrogen response element binding
  • Fidentical protein binding
  • Fnuclear receptor activity
  • Fnuclear steroid receptor activity
  • Fsequence-specific double-stranded DNA binding
  • Fsteroid binding

458 aa · 51 kDa · 5 isoforms

Biological roles

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

Nuclear receptor signallingGOTranscriptional regulationUniProt · GO
View supporting evidence

Nuclear receptor signalling

  • ·nuclear receptor activity

Transcriptional regulation

  • ·Orphan receptor that acts as a transcription activator in the absence of bound ligand. B…
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·DNA-templated transcription

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

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.

Afimoxifene
Narrow target profilePhase 2Antagonist

Estrogen-related receptor gamma antagonist

Direct interaction with this protein · 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 ESRRG

Gene-level evidence surfaced through the gene ESRRGthat 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.

Movement Disorders
0.78Well supported

Genetic evidence dominant · Open Targets 0.47

Risk-taking behaviour
0.69Moderately supported

Genetic evidence dominant · Open Targets 0.42

Atrial Fibrillation
0.66Moderately supported

Genetic evidence dominant · Open Targets 0.37

Intelligence
0.64Moderately supported

Genetic evidence dominant · Open Targets 0.39

Alcohol drinking
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.38

View evidence synthesis (5)
Movement DisordersWell supported
0.78
agreement 0.640.91
Genetic100%Literature0%

Open Targets aggregate 0.47 · 2 independent evidence families

Risk-taking behaviourModerately supported
0.69
agreement 0.570.81
Genetic100%

Open Targets aggregate 0.42 · 1 independent evidence family

Atrial FibrillationModerately supported
0.66
agreement 0.540.78
Genetic77%Animal model18%Literature5%

Open Targets aggregate 0.37 · 3 independent evidence families

IntelligenceModerately supported
0.64
agreement 0.520.76
Genetic100%

Open Targets aggregate 0.39 · 1 independent evidence family

Alcohol drinkingModerately supported
0.62
agreement 0.480.76
Genetic100%Literature1%

Open Targets aggregate 0.38 · 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
Movement Disorders0.47
Risk-taking behaviour0.42
Intelligence0.39
Alcohol drinking0.38
Breast Neoplasms0.37
Atrial Fibrillation0.37
Smoking initiation0.34
Attention Deficit Disorder with Hyperactivity0.33
Substance-Related Disorders0.33

Drug development

1 compounds recorded · 1 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: these count different sets and are not a subset relation.

View all recorded compounds (1)
AFIMOXIFENEPhase 2

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

Advanced Clinical 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 · Advanced ClinicalSM · 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

regulation of transcription factor activityToxCast

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

5

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.

ClinicalTrials.gov via the drug-target graph.