Protein / target

Mineralocorticoid receptor

NR3C2P08235Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
13
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Primary system

Endocrine & metabolic

Strongest disease association

autosomal dominant pseudohypoaldosteronism type 1

Genetic evidence · score 0.92

Therapeutic maturity

Clinically validated target

13 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

13 approved · 4 in clinical development

30 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

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Subcellular location

CytoplasmNucleusEndoplasmic reticulum membrane
Domains and Gene Ontology detail (21)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cendoplasmic reticulum membrane
  • Cnucleoplasm
  • Cnucleus
  • Creceptor complex
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Festrogen response element binding
  • Fnuclear receptor activity
  • Fnuclear steroid receptor activity
  • Fsequence-specific double-stranded DNA binding

984 aa · 107 kDa · 4 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingGO · ReactomeTranscriptional regulationGO · Reactome
View supporting evidence

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity
  • ·nuclear receptor-mediated steroid hormone signaling pathway

Transcriptional regulation

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·DNA-templated transcription
  • ·regulation of transcription by RNA polymerase II
View underlying pathways (3)

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.

NCOA1AGTFKBP4RENNR3C1HSD11B2ACEHSP90A…PTGES3HSP90A…NR3C2

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

3

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.

Spironolactone
Narrow target profileApprovedAntagonist

Mineralocorticoid receptor antagonist

Appears in clinical studies involving hypertensive disorder, nephrotic syndrome, heart failure, myocardial infarction

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

finerenone
Narrow target profileApprovedAntagonist

Mineralocorticoid receptor antagonist

Appears in clinical studies involving cardiovascular disorder, chronic kidney disease, heart failure, chronic kidney disease

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

Nimodipine
ApprovedAntagonist

Mineralocorticoid receptor antagonist

Appears in clinical studies involving cardiovascular disorder, subarachnoid hemorrhage, cocaine dependence, Mental deterioration

Direct interaction with this protein · 1 of 5 recorded protein targets

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.

autosomal dominant pseudohypoaldosteronism type 10.92

Genetic · overall 0.78

Renal pseudohypoaldosteronism type 10.86

Genetic · overall 0.73

hypertensive disorder0.84

Genetic · overall 0.74

pseudohyperaldosteronism type 20.79

Genetic · overall 0.69

Highest-confidence therapeutic associations

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

heart failure0.97

Clinical · overall 0.61

congestive heart failure0.96

Clinical · overall 0.59

myocardial infarction0.96

Clinical · overall 0.60

chronic kidney disease0.95

Clinical · overall 0.60

nephrotic syndrome0.93

Clinical · overall 0.58

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

type 2 diabetes mellitus0.59

Clinical

Show all associations
autosomal dominant pseudohypoaldosteronism type 10.78
hypertensive disorder0.74
Renal pseudohypoaldosteronism type 10.73
pseudohyperaldosteronism type 20.69
heart failure0.61
myocardial infarction0.60
chronic kidney disease0.60
congestive heart failure0.59
type 2 diabetes mellitus0.59
nephrotic syndrome0.58

Open Targets ranks 1,324 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 · 17 total

LY2623091Phase 2

chronic kidney disease · Hypertension · hypertensive disorder

XL550Approval

Hypertension · essential hypertension · hypertensive disorder

MT-3995Phase 2

diabetic kidney disease · metabolic dysfunction-associated steatohepatitis

FINERENONEApproval

cardiovascular disorder · chronic kidney disease · heart failure

DESOXYCORTICOSTERONE PIVALATEApproval

primary adrenal insufficiency

DESOXYCORTICOSTERONE ACETATEApproval
FLUDROCORTISONE ACETATEApproval

primary adrenal insufficiency · adrenogenital syndrome · chronic primary adrenal insufficiency

FELODIPINEApproval

hypertensive disorder · diabetes mellitus · cardiovascular disorder

DROSPIRENONEApproval

acne · Pain · Dysmenorrhea

CANRENONEApproval

cardiovascular disorder · acute respiratory distress syndrome · congestive heart failure

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · UniProt loc med confPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

regulation of steroid hormone biosynthetic processregulation of transcription factor activityregulation of steroid biosynthetic process

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.

Show remaining trials (24)

WITHDRAWN · via Nimodipine · NCT03150524

COMPLETED · via Nimodipine · NCT00000332

COMPLETED · via Spironolactone · NCT00523757

COMPLETED · via Spironolactone · NCT00498537

COMPLETED · via Spironolactone · NCT01602861

COMPLETED · via Spironolactone · NCT00865501

ClinicalTrials.gov via the drug-target graph.

Related literature

1

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

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.

hypertensive disorderWell supported
0.96
agreement 0.851.00
Genetic51%Clinical45%Literature5%

Open Targets aggregate 0.74 · 3 independent evidence families

autosomal dominant pseudohypoaldosteronism type 1Well supported
0.93
agreement 0.811.00
Genetic87%Animal model12%Literature2%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

Renal pseudohypoaldosteronism type 1Well supported
0.88
agreement 0.761.00
Genetic85%Animal model13%Literature2%Genetic literaturedup

Open Targets aggregate 0.73 · 3 independent evidence families · 1 not counted as duplicate

pseudohyperaldosteronism type 2Well supported
0.79
agreement 0.670.91
Genetic100%Genetic literaturedup

Open Targets aggregate 0.69 · 1 independent evidence family · 1 not counted as duplicate

nephrotic syndromeWell supported
0.77
agreement 0.640.90
Clinical74%Animal model25%Literature1%

Open Targets aggregate 0.58 · 3 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

15

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-11-15
    Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

    Cardiovascular diabetology · 2024 · 23 citations · Europe PMC · via finerenone

  2. New publication2024-09-01
    Finerenone in heart failure and chronic kidney disease with type 2 diabetes: FINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes.

    Nature medicine · 2024 · 80 citations · Europe PMC · via finerenone

  3. 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 Spironolactone

  4. Regulatory approval2023-05-26

    Approval: Qaialdo (EMA)

    ema · regulatory · ema · via Spironolactone

  5. Regulatory approval2022-02-16

    Approval: Kerendia (EMA)

    ema · regulatory · ema · via finerenone

  6. New publication2022-02-01
    Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis.

    European heart journal · 2022 · 719 citations · Europe PMC · via finerenone

  7. New publication2014-11-18
    Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.

    Circulation · 2015 · 811 citations · Europe PMC · via Spironolactone

  8. New publication2014-08-13
    Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial.

    Circulation. Heart failure · 2014 · 218 citations · Europe PMC · via Spironolactone

  9. New publication2014-04-01
    Spironolactone for heart failure with preserved ejection fraction.

    The New England journal of medicine · 2014 · 1,969 citations · Europe PMC · via Spironolactone

  10. New publication2013-11-18
    Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.

    Circulation. Heart failure · 2014 · 234 citations · Europe PMC · via Spironolactone

  11. New publication2012-12-20
    Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial.

    Circulation. Heart failure · 2013 · 157 citations · Europe PMC · via Spironolactone

  12. New publication2012-07-07
    The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

    Circulation. Arrhythmia and electrophysiology · 2012 · 12 citations · Europe PMC · via Spironolactone

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.