NR3C2

Chr 4AD

nuclear receptor subfamily 3 group C member 2

Also known as: MCR, MLR, MR, NR3C2VIT

This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to mineralocorticoid response elements in order to transactivate target genes. Mutations in this gene cause autosomal dominant pseudohypoaldosteronism type I, a disorder characterized by urinary salt wasting. Defects in this gene are also associated with early onset hypertension with severe exacerbation in pregnancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancyMIM #605115
Pseudohypoaldosteronism type I, autosomal dominantMIM #177735
AD
UniProtEarly-onset hypertension with severe exacerbation in pregnancy

Clinical highlights

Gene-disease validity (ClinGen)
pseudohyperaldosteronism type 2 · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
7
Active trials
90
Pubs (1 yr)
P/LP submissions
P/LP missense
0.35
LOEUF
LOF
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.35LOEUF
pLI 0.837
Z-score 4.79
OE 0.19 (0.110.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.10Z-score
OE missense 0.74 (0.680.81)
390 obs / 525.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.19 (0.110.35)
00.351.4
Missense OE?0.74 (0.680.81)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 8 / 41.2Missense obs/exp: 390 / 525.1Syn Z: -0.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NR3C2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Adrenal Gland NeoplasmHypertensionBone Diseases, Metabolic

Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks

RECRUITING
NCT03374215National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Started 2017-12-14
Type 1 Diabetes Mellitus

The MICRON Study - A Steno 1 Substudy

RECRUITING
NCT07270172University of AarhusStarted 2025-10-27
Diabetic NephropathiesKidney DiseasesRenal Insufficiency, Chronic

Transformative Research in Diabetic Nephropathy 2.0

RECRUITING
NCT07444203University of PennsylvaniaStarted 2025-11-12
Sodium-glucose cotransporter 2 inhibitors (SGLT2i)Renin-angiotensin-aldosterone system blockadeGlucagon-like peptide-1 receptor agonists (GLP 1 RA)
Transthyretin AmyloidosisATTR-CMATTRv-PN

Non-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis

RECRUITING
NCT06465810AstraZenecaStarted 2024-06-25
Treatment of transthyretin (ATTR) amyloidosis in observational study setting
Chronic Heart FailureHeart Failure With Reduced Ejection Fraction (HFrEF)Coronary Heart Disease (CHD)

Yiqi Fumai Lyophilized Injection for Chronic Heart Failure Caused by Coronary Heart Disease

NOT YET RECRUITING
NCT07803471Phase NAChina Academy of Chinese Medical SciencesStarted 2026-09
Yiqi Fumai Lyophilized Injection(YQFM)Stable Guideline-Directed Medical Therapy
HypertensionMineralocorticoid Excess

MR Antagonist and LSD1

ACTIVE NOT RECRUITING
NCT04840342Phase PHASE4Brigham and Women's HospitalStarted 2022-02-03
EplerenoneAmlodipine
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10