NR3C2

Summary

NR3C2 (nuclear receptor subfamily 3 group C member 2, HGNC:7979) is a protein-coding gene on chromosome 4q31.23, encoding Mineralocorticoid receptor (P08235). Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 4306 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant pseudohypoaldosteronism type 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 43
• Clinical variants (ClinVar): 465 total — 38 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 24 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 56 downstream targets (CollecTRI)
• MANE Select transcript: NM_000901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7979
Approved symbol	NR3C2
Name	nuclear receptor subfamily 3 group C member 2
Location	4q31.23
Locus type	gene with protein product
Status	Approved
Aliases	MR
Ensembl gene	ENSG00000151623
Ensembl biotype	protein_coding
OMIM	600983
Entrez	4306

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000342437, ENST00000344721, ENST00000358102, ENST00000503174, ENST00000503313, ENST00000504753, ENST00000511528, ENST00000512865, ENST00000625323, ENST00000870885, ENST00000870886, ENST00000870887, ENST00000870888

RefSeq mRNA: 3 — MANE Select: NM_000901 NM_000901, NM_001166104, NM_001354819

CCDS: CCDS3772, CCDS54811

Canonical transcript exons

ENST00000358102 — 9 exons

Exon	Start	End
ENSE00001221601	148435104	148436862
ENSE00002035974	148078764	148081499
ENSE00003544998	148120158	148120288
ENSE00003555231	148114104	148114261
ENSE00003558907	148154551	148154901
ENSE00003560923	148194746	148194862
ENSE00003580415	148259978	148260117
ENSE00003660663	148152469	148152613
ENSE00003847176	148442160	148442414

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 94.62.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6288 / max 80.6952, expressed in 708 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54284	1.0712	374
54283	0.6224	260
54285	0.5371	254
54290	0.4067	169
54291	0.3677	203
54286	0.3021	163
54287	0.2689	122
54289	0.0355	14
54279	0.0067	3
54281	0.0057	2

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	94.62	gold quality
colonic mucosa	UBERON:0000317	94.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.75	gold quality
rectum	UBERON:0001052	90.64	gold quality
middle temporal gyrus	UBERON:0002771	90.60	gold quality
choroid plexus epithelium	UBERON:0003911	90.57	gold quality
ileal mucosa	UBERON:0000331	90.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.99	gold quality
calcaneal tendon	UBERON:0003701	89.84	gold quality
jejunal mucosa	UBERON:0000399	89.80	gold quality
renal medulla	UBERON:0000362	88.90	gold quality
CA1 field of hippocampus	UBERON:0003881	88.75	gold quality
parotid gland	UBERON:0001831	88.60	gold quality
paraflocculus	UBERON:0005351	88.09	gold quality
frontal pole	UBERON:0002795	87.88	gold quality
colonic epithelium	UBERON:0000397	87.53	gold quality
middle frontal gyrus	UBERON:0002702	87.11	gold quality
biceps brachii	UBERON:0001507	86.98	gold quality
postcentral gyrus	UBERON:0002581	86.76	gold quality
jejunum	UBERON:0002115	86.22	gold quality
parietal lobe	UBERON:0001872	85.85	gold quality
renal glomerulus	UBERON:0000074	85.74	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.73	gold quality
cerebellar vermis	UBERON:0004720	85.51	gold quality
metanephric glomerulus	UBERON:0004736	85.42	gold quality
primary visual cortex	UBERON:0002436	85.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.11	gold quality
cranial nerve II	UBERON:0000941	84.93	gold quality
superior frontal gyrus	UBERON:0002661	84.56	gold quality
trigeminal ganglion	UBERON:0001675	84.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	45.82
E-ANND-3	yes	5.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

56 targets.

Target	Regulation
ACE	Activation
ADIPOQ	Unknown
ADRA1D
AGT	Activation
ATP1B1	Repression
BAX
BCL2
BDNF	Unknown
CABIN1	Repression
CALM1
CCN2
CCR5	Activation
CCR6	Activation
CD40	Activation
CDKN1A	Activation
CKM
CSN2	Repression
DOT1L
EDN1	Activation
EGFR	Activation
F13A1	Activation
FAF1
FGF2	Unknown
FGFR1
FKBP5	Repression
FN1	Activation
GADD45A	Activation
GAS6	Repression
HTR1A	Unknown
IL6	Activation

JASPAR motifs

Motif	Name	Family
MA0727.1	NR3C2	Steroid hormone receptors (NR3)
MA0727.2	NR3C2	Steroid hormone receptors (NR3)

JASPAR matrix evidence (PMIDs): PMID:15563547

Upstream regulators (CollecTRI, top): NFYC, NR3C1, PGR, SP1, STAT5A

miRNA regulators (miRDB)

250 targeting NR3C2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• chenodeoxycholic acid and deoxycholic acid, by inhibiting 11 beta HSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of Mineralocorticoid receptor (PMID:12015312)
• downregulation of MLR by aldosterone (PMID:12125101)
• cortisone and 11-dehydrocorticosterone, the main cortisol and corticosterone metabolites produced in the distal nephron, where sodium reabsorption stimulated by aldosterone takes place, bind with high affinity to S810L mineralocorticoid receptor (PMID:12538613)
• Two frameshift mutations in exon 2 and one nonsense mutation in exon 4 (generate truncated proteins due to premature stop codons. Three missense mutations ) differently affect hMR function. DNA binding domain mutant has reduced maximal transactivation. (PMID:12788847)
• PIAS1 conjugates SUMO-1 to human mineralocorticoid receptor. (PMID:14500761)
• glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells (PMID:14617569)
• MR is expressed through alternative translation initiation, as distinct protein variants which possess different functional properties (PMID:15080790)
• The S810L missense mutation of the mineralocorticoid receptor does not play a major role in the etiology of pregnancy-induced hypertension in a German /Turkish population. (PMID:15117605)
• Results reveal differential modulatory roles of the protein inhibitor of activated STAT proteins on the transcriptional properties of mineralocorticoid and glucocorticoid receptors. (PMID:15171715)
• Missense mutations of the human mineralocorticoid receptor disclose important residues involved in DNA binding, intracellular trafficking, and ligand binding. (PMID:15192075)
• These findings demonstrate a coupling between MR up-regulation and transcriptional hyperactivity. (PMID:15666800)
• our findings suggest a novel interplay between cAMP and MR signaling pathways; the N-terminal and the DNA binding domains of hMR are essential for enhancement of the catecholamine signal transduction pathway (PMID:15713533)
• The endogenous vascular smooth muscle MR mediates angiotensin II- and aldosterone-dependent gene expression, including several involved in vascular fibrosis, inflammation, and calcification. (PMID:15718497)
• MR is a nuclear hormone receptor whose unidirectional transfer to the nucleus may be regulated through multiple pathways (PMID:15737989)
• mineralocorticoid receptor has a ligand-dependent interaction with coactivator and corepressor peptides (PMID:15761029)
• The MR contribution to nongenotropic effects of aldosterone was shown. (PMID:15761031)
• The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension. Site directed mutagenesis studies. (PMID:15908963)
• human MR activation in cardiomyocytes of transgenic mice induced defects in heart function, leading to early sudden death. Surviving animals exhibited major ECG abnormalities (PMID:15939817)
• Results explain the potency of mineralocorticoid receptor activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone. (PMID:15967794)
• Findings provide critical insights into the molecular basis of hormone binding and coactivator recognition by MR and related steroid receptors. (PMID:16061183)
• aldosterone/MR activation is linked to renal inflammation and proteinuria (PMID:16145013)
• Receptor antagonism by spironolactone ameliorated LV diastolic dysfunction and reduced chamber stiffness in association with regression of myocardial fibrosis in mildly symptomatic patients with dilated cardiomyopathy. (PMID:16275882)
• These observations, for the first time, revealed a novel role for MR and its ligands in the regulation of de novo glucose synthesis in hepatocytes. (PMID:16516149)
• Six new heterozygous NR3C2 mutations were detected associated with pseudohypoaldosteronism type 1. (PMID:16954160)
• Results shows that the mRNA expression of MR in spermatozoa is lower than in mononuclear leukocytes. (PMID:16964418)
• Cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the NR3C2 MR180V variant. (PMID:17018659)
• Ubc9 has a role as a transcriptional MR coactivator, beyond the known SUMO E2-conjugating enzyme (PMID:17105732)
• no differences in cognitive functioning were observed dependent on the polymorphisms in the MR and GR genes in older adults; I180V variant in the MR gene influenced the prevalence of depressive symptoms, independently from cognitive functioning (PMID:17133261)
• The effect the different distribution of the c.722T single nucleotide polymorphism is not clear to date. (PMID:17287415)
• Aldosterone leads to enhanced EGFR expression via interaction with EGFR promoter, which is mineralocorticoid receptor specific and could contribute to the aldosterone-induced increase in fibronectin abundance. (PMID:17311890)
• The data suggest that the overall transcriptional activity of MR can be modulated by its sumoylation potential as well as the sumoylation level of MR-interacting proteins, and requires the continuous function of the proteasome. (PMID:17314004)
• Aldosterone promotes tubular cell apoptosis in a dose- and time-dependent manner. This effect of aldosterone is mediated through MR and associated with generation of ROS. (PMID:17670905)
• expression in mice of hMR throughout gestation resulted in early postnatal death; wen hMR expression was initiated after birth double-transgenic mice developed progressive alopecia and hair follicle cysts (PMID:17675581)
• reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR. (PMID:17703341)
• Data show that aldosterone increases elastin production via a mineralocorticoid receptor-independent pathway involving insulin-like growth factor-I receptor signaling. (PMID:17724138)
• both mineralocorticoid and glucocorticoid receptors may be involved in the multiple mechanisms controlling counterregulatory responses to hypoglycemia in healthy man (PMID:18182467)
• nongenomic MR signaling is mediated by the EF domains and present the first proof of principle showing that nongenomic signaling can be sufficient for some pathophysiological effects (PMID:18184651)
• Our study indicates MR and 11beta-HSD2 are both sensitive and specific markers of the distal nephron and its related neoplasms (chromophobe renal cell carcinomas and oncocytomas). (PMID:18408592)
• Here, we show that human coronary artery and aortic ECs express MR mRNA and protein and that EC MR mediates aldosterone-dependent gene transcription. (PMID:18467630)
• The MR rs5522 (I180V) minor allele was found more often in fibromyalgia patients than in controls. (PMID:18468809)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr3c2	ENSDARG00000102082
mus_musculus	Nr3c2	ENSMUSG00000031618
rattus_norvegicus	Nr3c2	ENSRNOG00000034007
drosophila_melanogaster	ERR	FBGN0035849

Paralogs (8): PGR (ENSG00000082175), ESR1 (ENSG00000091831), NR3C1 (ENSG00000113580), ESRRB (ENSG00000119715), ESR2 (ENSG00000140009), AR (ENSG00000169083), ESRRA (ENSG00000173153), ESRRG (ENSG00000196482)

Protein

Protein identifiers

Mineralocorticoid receptor — P08235 (reviewed: P08235)

Alternative names: Nuclear receptor subfamily 3 group C member 2

All UniProt accessions (3): P08235, B0ZBF6, B0ZBF8

UniProt curated annotations — full annotation on 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.

Subunit / interactions. Heteromultimeric cytoplasmic complex with HSP90, HSP70, and FKBP4, in the absence of ligand. After ligand binding, it translocates to the nucleus and binds to DNA as a homodimer and as a heterodimer with NR3C1. May interact with HSD11B2 in the absence of ligand. Binds the coactivators NCOA1, NCOA2, TIF1 and NRIP1.

Subcellular location. Cytoplasm. Nucleus. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes.

Post-translational modifications. Phosphorylated.

Disease relevance. Pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735] A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. The disease is caused by variants affecting the gene represented in this entry. Early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115] Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Miscellaneous. Lacks steroid-binding activity and acts as ligand-independent transactivator.

Similarity. Belongs to the nuclear hormone receptor family. NR3 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P08235-1	1	yes
P08235-2	2
P08235-3	3
P08235-4	4, Delta

RefSeq proteins (3): NP_000892, NP_001159576, NP_001341748 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050200	Nuclear_hormone_rcpt_NR3	Family

Pfam: PF00104, PF00105

UniProt features (108 total): sequence variant 21, binding site 20, mutagenesis site 18, helix 15, region of interest 6, strand 6, modified residue 5, compositionally biased region 4, splice variant 4, turn 3, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
4PF3	X-RAY DIFFRACTION	1.1
3VHV	X-RAY DIFFRACTION	1.35
3WFG	X-RAY DIFFRACTION	1.4
9GC7	X-RAY DIFFRACTION	1.46
6GEV	X-RAY DIFFRACTION	1.54
6GGG	X-RAY DIFFRACTION	1.71
2AAX	X-RAY DIFFRACTION	1.75
5MWY	X-RAY DIFFRACTION	1.75
6GG8	X-RAY DIFFRACTION	1.8
5MWP	X-RAY DIFFRACTION	1.82
5L7H	X-RAY DIFFRACTION	1.84
2AB2	X-RAY DIFFRACTION	1.85
5L7E	X-RAY DIFFRACTION	1.86
2A3I	X-RAY DIFFRACTION	1.95
2AA2	X-RAY DIFFRACTION	1.95
2AA6	X-RAY DIFFRACTION	1.95
1Y9R	X-RAY DIFFRACTION	1.96
5L7G	X-RAY DIFFRACTION	2.01
4UDA	X-RAY DIFFRACTION	2.03
3WFF	X-RAY DIFFRACTION	2.05
3VHU	X-RAY DIFFRACTION	2.11
2AA5	X-RAY DIFFRACTION	2.2
2AA7	X-RAY DIFFRACTION	2.2
2OAX	X-RAY DIFFRACTION	2.29
2ABI	X-RAY DIFFRACTION	2.33
1YA3	X-RAY DIFFRACTION	2.34
4UDB	X-RAY DIFFRACTION	2.36
4TNT	X-RAY DIFFRACTION	2.39
5HCV	X-RAY DIFFRACTION	2.5
6L88	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08235-F1	56.96	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 603; 606; 620; 623; 639; 645; 655; 658; 770; 770; 770; 776 …

Post-translational modifications (5): 250, 259, 283, 287, 299

Mutagenesis-validated functional residues (18):

Position	Phenotype
767	loss of transcription transactivation.
767	strong decrease of transcription transactivation.
770	abolishes aldosterone binding and transcription transactivation.
776	reduces aldosterone binding and transcription transactivation.
782	decreased coactivator binding.
785	loss of coactivator binding.
796	decreased coactivator binding.
808	increases aldosterone-binding.
810	alters receptor specificity.
817	reduces aldosterone binding and transcription transactivation.
849	strongly decreases affinity for aldosterone and transcription transactivation.
942	abolishes steroid binding and transcription transactivation.
945	decreases aldosterone-binding and cortisol-binding.
952	reduces transcription transactivation.
953	slightly reduces aldosterone binding and abolishes transcription transactivation.
954	reduces aldosterone binding and abolishes transcription transactivation.
956	abolishes aldosterone binding and transcription transactivation.
957	slightly reduces aldosterone binding and transcription transactivation.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 349 (showing top): MORF_ITGA2, E2F_Q4_01, AAGCAAT_MIR137, ZHAN_MULTIPLE_MYELOMA_PR_DN, CCAWYNNGAAR_UNKNOWN, SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, CMYB_01, MORF_BRCA1, AAGCCAT_MIR135A_MIR135B, MODULE_404, CAGCTG_AP4_Q5, MORF_RAD51L3, ATGTTAA_MIR302C, GTGCCTT_MIR506

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), signal transduction (GO:0007165), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), regulation of DNA-templated transcription (GO:0006355), cellular response to hormone stimulus (GO:0032870), response to lipid (GO:0033993)

GO Molecular Function (14): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), steroid binding (GO:0005496), zinc ion binding (GO:0008270), TBP-class protein binding (GO:0017025), estrogen response element binding (GO:0034056), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), lipid binding (GO:0008289), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cellular responses to stress	1
SUMO E3 ligases SUMOylate target proteins	1
Generic Transcription Pathway	1
Cellular responses to stimuli	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of DNA-templated transcription	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
transcription by RNA polymerase II	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
response to chemical	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
nuclear receptor activity	1
nuclear receptor-mediated steroid hormone signaling pathway	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
lipid binding	1
transition metal ion binding	1
general transcription initiation factor binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
double-stranded DNA binding	1

Protein interactions and networks

STRING

2108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR3C2	AGT	P01019	946
NR3C2	REN	P00797	945
NR3C2	HSD11B2	P80365	918
NR3C2	ACE	P12821	892
NR3C2	SCNN1G	P51170	857
NR3C2	MMEL1	Q495T6	840
NR3C2	HSD11B1	P28845	801
NR3C2	SCNN1B	P51168	796
NR3C2	CYP11B2	P19099	792
NR3C2	MME	P08473	761
NR3C2	SCNN1A	P37088	744
NR3C2	NR3C1	P04150	725
NR3C2	POMC	P01189	725
NR3C2	FKBP4	Q02790	721
NR3C2	APEH	P13798	720

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
TESMIN	NR3C2	psi-mi:“MI:0915”(physical association)	0.580
PPARGC1A	NR3C2	psi-mi:“MI:0915”(physical association)	0.510
NCOA1	NR3C2	psi-mi:“MI:0915”(physical association)	0.510
NR3C2	NCOA1	psi-mi:“MI:0915”(physical association)	0.510
HSP90AB1	NR3C2	psi-mi:“MI:0915”(physical association)	0.400
RABAC1	NR3C2	psi-mi:“MI:0915”(physical association)	0.370
NR3C2	ACSL1	psi-mi:“MI:0915”(physical association)	0.370
NR3C2	RXRA	psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CARNMT1	LENG9	psi-mi:“MI:0914”(association)	0.350
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (60): NR3C2 (Affinity Capture-MS), PSMC5 (Two-hybrid), NCOA1 (Affinity Capture-Western), NCOA1 (Two-hybrid), CREBBP (Affinity Capture-Western), EP300 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), NR3C2 (Affinity Capture-Western), NR3C2 (Affinity Capture-MS), NR3C2 (Affinity Capture-Western), NR3C2 (Affinity Capture-Western), PPP1CA (Affinity Capture-Western), FAF1 (Two-hybrid), DAXX (Two-hybrid), CASP8AP2 (Two-hybrid)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JN51, A0JP82, A2AWL7, A2BGM5, A2RRX6, F8VPJ6, K9JHZ4, O13186, O46567, O54826, O89091, P04150, P08235, P15822, P22199, P32519, P36197, P37275, P48552, P55197, P59759, P79269, P79686, Q29131, Q2KHR2, Q3YC04, Q4JM28, Q5R9P5, Q60775, Q61321, Q62947, Q64318, Q68DE3, Q6XLJ0, Q8AYC1, Q8AYC2, Q8BMA5, Q8IZQ8

Diamond homologs: A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW16, A7XW20, A7XW25, O08537, O08580, O13012, O13186, O46567, O73673, O95718, O97775, O97776, O97952, O97960, P03372, P04150, P06186, P06211, P06212, P06401, P06536, P06537, P07812, P08235, P10275, P11474, P11475, P15207, P16058, P19091

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
NR3C2	“down-regulates quantity by repression”	ATP1B1	“transcriptional regulation”
MAPK1	“down-regulates quantity by destabilization”	NR3C2	phosphorylation
MAPK3	“down-regulates quantity by destabilization”	NR3C2	phosphorylation
GRK5	down-regulates	NR3C2	phosphorylation
NR3C1	up-regulates	NR3C2
drospirenone	“down-regulates activity”	NR3C2	“chemical inhibition”
spironolactone	“down-regulates activity”	NR3C2	“chemical inhibition”
eplerenone	“down-regulates activity”	NR3C2	“chemical inhibition”
nimodipine	“down-regulates activity”	NR3C2	“chemical inhibition”
felodipine	“down-regulates activity”	NR3C2	“chemical inhibition”
Nitrendipine	“down-regulates activity”	NR3C2	“chemical inhibition”
progesterone	“down-regulates activity”	NR3C2	“chemical inhibition”
fludrocortisone	“up-regulates activity”	NR3C2	“chemical activation”
cortisol	“up-regulates activity”	NR3C2	“chemical activation”
dexamethasone	“down-regulates activity”	NR3C2	“chemical inhibition”
aldosterone	“up-regulates activity”	NR3C2	“chemical activation”
11-deoxycorticosterone	“up-regulates activity”	NR3C2	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

465 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	17
Uncertain significance	253
Likely benign	65
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1678530	NM_000901.5(NR3C2):c.1819delinsTT (p.Gly607fs)	Pathogenic
1809717	NM_000901.5(NR3C2):c.2194C>T (p.Arg732Ter)	Pathogenic
1809718	NM_000901.5(NR3C2):c.2457C>A (p.Tyr819Ter)	Pathogenic
252501	NM_000901.5(NR3C2):c.1409C>A (p.Ser470Ter)	Pathogenic
2578204	NM_000901.5(NR3C2):c.556_557del (p.Met186fs)	Pathogenic
3068908	NC_000004.11:g.(149041440_149073619)_(149116014_149181129)del	Pathogenic
3590196	NM_000901.5(NR3C2):c.1954C>T (p.Arg652Ter)	Pathogenic
3640878	NM_000901.5(NR3C2):c.2205del (p.Pro736fs)	Pathogenic
3707530	NM_000901.5(NR3C2):c.2455T>G (p.Tyr819Asp)	Pathogenic
3720593	NM_000901.5(NR3C2):c.2581C>T (p.Arg861Ter)	Pathogenic
3729624	NM_000901.5(NR3C2):c.354del (p.Tyr119fs)	Pathogenic
3897570	NM_000901.5(NR3C2):c.2860del (p.Lys953_Val954insTer)	Pathogenic
3906996	NM_000901.5(NR3C2):c.2532del (p.Met845fs)	Pathogenic
4056460	NM_000901.5(NR3C2):c.1685C>A (p.Ser562Ter)	Pathogenic
4280062	NM_000901.5(NR3C2):c.2509_2510+2del	Pathogenic
429751	NM_000901.5(NR3C2):c.1768C>T (p.Arg590Ter)	Pathogenic
430357	NM_000901.5(NR3C2):c.1951C>T (p.Arg651Ter)	Pathogenic
4526591	NM_000901.5(NR3C2):c.2899C>T (p.Gln967Ter)	Pathogenic
4820298	NM_000901.5(NR3C2):c.358G>T (p.Glu120Ter)	Pathogenic
562976	GRCh37/hg19 4q31.23(chr4:149309976-149452658)x1	Pathogenic
686678	GRCh37/hg19 4q31.23(chr4:149087640-149284001)x1	Pathogenic
8553	NM_000901.5(NR3C2):c.1004del (p.Ser335fs)	Pathogenic
8554	NM_000901.5(NR3C2):c.1375del (p.Ser459fs)	Pathogenic
8555	NM_000901.5(NR3C2):c.1609C>T (p.Arg537Ter)	Pathogenic
8556	NM_000901.5(NR3C2):c.2365+3del	Pathogenic
8558	NM_000901.5(NR3C2):c.2871dup (p.Ala958fs)	Pathogenic
8560	NM_000901.5(NR3C2):c.1131dup (p.Glu378Ter)	Pathogenic
8561	NM_000901.5(NR3C2):c.315_322del (p.Met105fs)	Pathogenic
8562	NM_000901.5(NR3C2):c.1935C>A (p.Cys645Ter)	Pathogenic
8563	NM_000901.5(NR3C2):c.2327A>G (p.Gln776Arg)	Pathogenic

SpliceAI

3197 predictions. Top by Δscore:

Variant	Effect	Δscore
4:148081496:CCAG:C	acceptor_gain	1.0000
4:148081497:CAGC:C	acceptor_gain	1.0000
4:148114096:CTACT:C	donor_loss	1.0000
4:148114098:ACT:A	donor_loss	1.0000
4:148114099:CTC:C	donor_loss	1.0000
4:148114100:TCACG:T	donor_loss	1.0000
4:148114101:CACGT:C	donor_loss	1.0000
4:148114102:A:AC	donor_gain	1.0000
4:148114102:ACGT:A	donor_gain	1.0000
4:148114103:C:CA	donor_gain	1.0000
4:148114103:C:G	donor_loss	1.0000
4:148114103:CGT:C	donor_gain	1.0000
4:148114103:CGTC:C	donor_gain	1.0000
4:148114262:C:CC	acceptor_gain	1.0000
4:148114264:G:C	acceptor_gain	1.0000
4:148120156:A:AC	donor_gain	1.0000
4:148120157:C:CC	donor_gain	1.0000
4:148120166:A:AC	donor_gain	1.0000
4:148120166:AGTAG:A	donor_gain	1.0000
4:148120178:A:C	donor_gain	1.0000
4:148120182:T:A	donor_gain	1.0000
4:148152467:A:AC	donor_gain	1.0000
4:148152468:C:CC	donor_gain	1.0000
4:148152468:CT:C	donor_gain	1.0000
4:148194741:CTTA:C	donor_loss	1.0000
4:148194742:TTAC:T	donor_loss	1.0000
4:148194743:TAC:T	donor_loss	1.0000
4:148194744:A:AC	donor_gain	1.0000
4:148194744:AC:A	donor_gain	1.0000
4:148194744:ACCT:A	donor_gain	1.0000

AlphaMissense

6445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:148152481:A:G	L833P	1.000
4:148154569:A:G	W783R	1.000
4:148154569:A:T	W783R	1.000
4:148194756:C:A	M668I	1.000
4:148194756:C:G	M668I	1.000
4:148194756:C:T	M668I	1.000
4:148194757:A:G	M668T	1.000
4:148194760:C:A	G667V	1.000
4:148194760:C:T	G667E	1.000
4:148194764:C:G	A666P	1.000
4:148194771:A:C	C663W	1.000
4:148194772:C:A	C663F	1.000
4:148194772:C:G	C663S	1.000
4:148194772:C:T	C663Y	1.000
4:148194773:A:G	C663R	1.000
4:148194773:A:T	C663S	1.000
4:148194783:T:A	R659S	1.000
4:148194783:T:G	R659S	1.000
4:148194784:C:A	R659I	1.000
4:148194784:C:G	R659T	1.000
4:148194785:T:C	R659G	1.000
4:148194786:G:C	C658W	1.000
4:148194787:C:A	C658F	1.000
4:148194787:C:G	C658S	1.000
4:148194787:C:T	C658Y	1.000
4:148194788:A:C	C658G	1.000
4:148194788:A:G	C658R	1.000
4:148194788:A:T	C658S	1.000
4:148194795:A:C	C655W	1.000
4:148194796:C:A	C655F	1.000

dbSNP variants (sampled 300 via entrez): RS1000002470 (4:148159625 G>A,C), RS1000034549 (4:148153079 A>G), RS1000039229 (4:148306760 T>C,G), RS1000045180 (4:148351927 C>T), RS1000051870 (4:148374049 T>C), RS1000056207 (4:148434432 T>C), RS1000057065 (4:148169047 A>C), RS1000060107 (4:148301349 C>G,T), RS1000060353 (4:148229212 A>G), RS1000068952 (4:148415801 G>T), RS1000076126 (4:148351639 C>A,T), RS1000079378 (4:148286835 A>G), RS1000080117 (4:148244305 G>C), RS1000086403 (4:148175191 C>A,T), RS1000089610 (4:148347785 GTAATAA>G,GTAA,GTAATAATAA)

Disease associations

OMIM: gene MIM:600983 | disease phenotypes: MIM:605115, MIM:177735

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant pseudohypoaldosteronism type 1	Definitive	Autosomal dominant
pseudohyperaldosteronism type 2	Limited	Unknown

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pseudohyperaldosteronism type 2	Limited	AD
autosomal dominant pseudohypoaldosteronism type 1	Definitive	AD

Mondo (5): pseudohyperaldosteronism type 2 (MONDO:0011517), autosomal dominant pseudohypoaldosteronism type 1 (MONDO:0008329), myoepithelial tumor (MONDO:0002380), pseudohypoaldosteronism (MONDO:0018638), autism spectrum disorder (MONDO:0005258)

Orphanet (5): Hypertension due to gain-of-function mutations in the mineralocorticoid receptor (Orphanet:88660), Renal pseudohypoaldosteronism type 1 (Orphanet:171871), Pseudohypoaldosteronism type 1 (Orphanet:756), Pseudohypoaldosteronism (Orphanet:444916), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000822	Hypertension
HP:0000841	Hyperactive renin-angiotensin system
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0001508	Failure to thrive
HP:0001942	Metabolic acidosis
HP:0001944	Dehydration
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002153	Hyperkalemia
HP:0002615	Hypotension
HP:0002902	Hyponatremia
HP:0003351	Decreased circulating renin concentration
HP:0003623	Neonatal onset
HP:0004319	Decreased circulating aldosterone concentration
HP:0008071	Maternal hypertension
HP:0008242	Pseudohypoaldosteronism
HP:0011968	Feeding difficulties

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000328_16	Biochemical measures	3.000000e-06
GCST001487_3	Thyroid function	3.000000e-10
GCST001521_1	Subcutaneous adipose tissue	1.000000e-06
GCST001806_5	Corneal structure	4.000000e-08
GCST001856_34	Thyroid hormone levels	9.000000e-16
GCST001856_55	Thyroid hormone levels	2.000000e-13
GCST002337_13	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST003427_173	Alzheimer disease and age of onset	6.000000e-07
GCST003988_10	Hypothyroidism	8.000000e-18
GCST004276_3	Plasma thyroid-stimulating hormone levels	2.000000e-11
GCST004276_5	Plasma thyroid-stimulating hormone levels	6.000000e-08
GCST005667_5	Central corneal thickness	8.000000e-09
GCST006275_3	Vestibular neuritis	2.000000e-09
GCST006463_8	Urinary albumin excretion (no hypertensive medication)	1.000000e-08
GCST006586_13	Urinary albumin excretion	7.000000e-12
GCST006988_105	Blond vs. brown/black hair color	3.000000e-12
GCST008165_4	Thyroid stimulating hormone levels	5.000000e-32
GCST008790_19	Urinary albumin-to-creatinine ratio	5.000000e-14
GCST008791_19	Microalbuminuria	1.000000e-10
GCST008794_58	Urinary albumin-to-creatinine ratio	6.000000e-13
GCST009260_4	Hippocampal volume	8.000000e-06
GCST009640_46	Urinary albumin-to-creatinine ratio	3.000000e-12
GCST010485_8	Platelet reactivity in response to clopidogrel treatment	3.000000e-07
GCST010566_5	Benign childhood epilepsy with centro-temporal spikes	9.000000e-06
GCST010653_69	Thyroid stimulating hormone levels	7.000000e-93
GCST010796_4301	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4302	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4303	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_4392	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4393	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004296	thyroid function
EFO:0004345	corneal topography
EFO:0004730	hormone measurement
EFO:0004847	age at onset
EFO:0005213	central corneal thickness
EFO:0004285	albuminuria
EFO:0003924	hair color
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005035	hippocampal volume
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D011546	Pseudohypoaldosteronism	C12.050.351.968.419.815.770; C12.200.777.419.815.770; C12.950.419.815.770; C16.320.831.770
C565359	Hypertension, Early-Onset, Autosomal Dominant, with Severe Exacerbation in Pregnancy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1994 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,195,114 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1095097	EPLERENONE	4	13,067
CHEMBL1276308	MIFEPRISTONE	4	30,535
CHEMBL131	PREDNISOLONE	4	140,604
CHEMBL1370	BUDESONIDE	4	72,936
CHEMBL1393	SPIRONOLACTONE	4	49,171
CHEMBL1473	FLUTICASONE PROPIONATE	4	60,190
CHEMBL1676	FLUTICASONE FUROATE	4	1,493
CHEMBL1683	HYDROCORTISONE BUTYRATE	4	14,031
CHEMBL2181927	FINERENONE	4	750
CHEMBL384467	DEXAMETHASONE	4	279,102
CHEMBL389621	HYDROCORTISONE	4	207,645
CHEMBL717	MEDROXYPROGESTERONE ACETATE	4	51,452
CHEMBL110739	CORTICOSTERONE	3	28,274
CHEMBL267431	ASOPRISNIL	3	1,789
CHEMBL3916929	BALCINRENONE	3	132
CHEMBL166444	METRIBOLONE	2	1,779
CHEMBL1908373	ONAPRISTONE	2	29,218
CHEMBL2181929	MT-3995	2	261
CHEMBL273453	ALDOSTERONE	2	50,544
CHEMBL27769	STANOLONE	2
CHEMBL4088896	LY2623091	2
CHEMBL454138	TUROFEXORATE ISOPROPYL	2
CHEMBL1215331	PF-03882845	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs5522	Efficacy	3	enalapril	Hypertension

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5522	NR3C2	3	2.75	1	enalapril
rs2070950	NR3C2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 3C. 3-Ketosteroid receptors

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
progesterone	Antagonist	11.0	pIC50
deoxycorticosterone	Agonist	11.0	pIC50
aldosterone	Agonist	10.0	pIC50
cortisol	Agonist	9.95	pIC50
fludrocortisone	Agonist	9.92	pIC50
dexamethasone	Agonist	9.0	pIC50
spironolactone	Antagonist	8.63	pKi
esaxerenone	Antagonist	8.62	pIC50
ocedurenone	Antagonist	8.57	pIC50
PF-03882845	Antagonist	8.04	pIC50
budesonide	Agonist	7.85	pEC50
finerenone	Antagonist	7.74	pIC50
prednisolone	Agonist	7.43	pKi
apararenone	Antagonist	7.0	pKi
fluticasone propionate	Agonist	6.83	pEC50
nimodipine	Antagonist	6.8	pIC50
balcinrenone	Antagonist	6.4	pIC50
eplerenone	Antagonist	6.4	pIC50
onapristone	Antagonist	6.33	pIC50
AZD9567	Agonist	4.42	pIC50

Binding affinities (BindingDB)

110 measured of 113 human assays (113 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
dexamethasone (tetramethyl-rhodamine conjugated )	EC50	0.2 nM
(1S,2R,10S,11S,14S,15R,17S)-17-hydroxy-14-(2-hydroxyacetyl)-2-methyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-15-carbaldehyde	EC50	0.47 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] 2-phenylacetate	EC50	2.85 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
(1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one	EC50	2.9 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
Hydrocortisone Butyrate	EC50	2.94 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] propanoate	EC50	3.17 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[4-[2-(4-fluoro-2-methylphenyl)ethyl]-2-pyridinyl]urea	IC50	4.7 nM	US-8722709: Mineralocorticoid receptor antagonists
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] heptanoate	EC50	5.27 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] hexanoate	EC50	5.68 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[4-[2-(2-methylphenyl)ethyl]-2-pyridinyl]urea	IC50	7.1 nM	US-8722709: Mineralocorticoid receptor antagonists
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] benzoate	EC50	7.46 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
Mifeprex	IC50	8.8 nM
[4-[2-(4-chlorophenyl)pyrazol-3-yl]-2-pyridinyl]urea	IC50	9.4 nM	US-8722709: Mineralocorticoid receptor antagonists
2-[(3S)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide	IC50	9.5 nM	US-9394291: Benzoxazinone amides as mineralocorticoid receptor modulators
2-[7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	IC50	10 nM	US-9394291: Benzoxazinone amides as mineralocorticoid receptor modulators
2-[(3R)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	IC50	10 nM	US-10017502: Benzoxazinone amides as mineralocorticoid receptor modulators
[4-[2-(2-methylphenyl)propyl]-2-pyridinyl]urea	IC50	11 nM	US-8722709: Mineralocorticoid receptor antagonists
US9034856, 6	IC50	11 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
[4-(2,2-diphenylethyl)-2-pyridinyl]urea	IC50	13 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-[2-(trifluoromethyl)phenyl]ethyl]-2-pyridinyl]urea	IC50	13 nM	US-8722709: Mineralocorticoid receptor antagonists
2-[7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	IC50	13 nM	US-9394291: Benzoxazinone amides as mineralocorticoid receptor modulators
2-[(3R)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	IC50	13 nM	US-10017502: Benzoxazinone amides as mineralocorticoid receptor modulators
[4-[2-(4-methylphenyl)pyrazol-3-yl]-2-pyridinyl]urea	IC50	14 nM	US-8722709: Mineralocorticoid receptor antagonists
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] 2-methylpropanoate	EC50	15.6 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
2-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide	IC50	16 nM	US-9394291: Benzoxazinone amides as mineralocorticoid receptor modulators
[4-[2-cyclopropyl-2-(2-methylphenyl)ethyl]-2-pyridinyl]urea	IC50	22 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(4-methoxyphenyl)pyrazol-3-yl]-2-pyridinyl]urea	IC50	25 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(2-methoxyphenyl)ethyl]-2-pyridinyl]urea	IC50	25 nM	US-8722709: Mineralocorticoid receptor antagonists
(8R,9S,10R,13S,14S,17R)-13-methylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-2H-furan]-3-one	IC50	26 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
Drospirenone	IC50	27 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
[4-[2-(4-fluorophenyl)ethyl]-2-pyridinyl]urea	IC50	30 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-(2-phenylpropyl)-2-pyridinyl]urea	IC50	33 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-(2-phenylethyl)-2-pyridinyl]urea	IC50	37 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(4-fluoro-2-methylphenyl)pyrazol-3-yl]-2-pyridinyl]urea	IC50	38 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrazol-5-yl]-2-pyridinyl]urea	IC50	47 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(2-methylphenyl)-2-phenylethyl]-2-pyridinyl]urea	IC50	54 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(4-fluorophenyl)pyrazol-3-yl]-2-pyridinyl]urea	IC50	62 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-[3-(trifluoromethyl)phenyl]ethyl]-2-pyridinyl]urea	IC50	73 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(2-fluorophenyl)ethyl]-2-pyridinyl]urea	IC50	76 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-(3-methylphenyl)ethyl]-2-pyridinyl]urea	IC50	78 nM	US-8722709: Mineralocorticoid receptor antagonists
dihydroquinoline-based ligand, 37	IC50	84 nM
[4-[2-(3-fluorophenyl)ethyl]-2-pyridinyl]urea	IC50	86 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-(2-cyclopropyl-2-phenylethyl)-2-pyridinyl]urea	IC50	100 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[2-[4-(trifluoromethyl)phenyl]ethyl]-2-pyridinyl]urea	IC50	100 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[4-(4-fluorophenyl)-1,3-oxazol-5-yl]-2-pyridinyl]urea	IC50	110 nM	US-8722709: Mineralocorticoid receptor antagonists
(18Z)-12-methoxy-18-({3-[(1E)-1-(methoxyimino)ethyl]thiophen-2-yl}methylidene)-3,5,5-trimethyl-17-oxa-6-azatetracyclo[8.8.0.0^{2,7}.0^{11,16}]octadeca-1(10),2(7),3,8,11,13,15-heptaen-13-ol	KI	110 nM
6-(2-methoxyphenyl)-2,2-dimethyl-4-[1-(prop-2-en-1-yloxy)ethyl]-1,2-dihydroquinoline	IC50	116 nM
[4-[1-phenyl-3-(trifluoromethyl)pyrazol-5-yl]-2-pyridinyl]urea	IC50	130 nM	US-8722709: Mineralocorticoid receptor antagonists
[4-[5-(4-fluorophenyl)-3-methylimidazol-4-yl]-2-pyridinyl]urea	IC50	130 nM	US-8722709: Mineralocorticoid receptor antagonists
(8R,9S,10R,13S,14S,17R)-13-methylspiro[1,2,8,9,10,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-17,5’-2H-furan]-3-one	IC50	130 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative

ChEMBL bioactivities

1260 potent at pChembl≥5 of 1271 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05012	nM	CHEMBL4532472
10.10	Ki	0.08	nM	CHEMBL4095917
9.74	EC50	0.18	nM	ALDOSTERONE
9.64	Ki	0.23	nM	CHEMBL4086416
9.54	Ki	0.29	nM	PREDNISOLONE
9.52	IC50	0.305	nM	ALDOSTERONE
9.50	Ki	0.3162	nM	CHEMBL4572476
9.50	Ki	0.319	nM	CHEMBL235206
9.48	Ki	0.33	nM	LY2623091
9.47	Ki	0.342	nM	CHEMBL3120319
9.47	EC50	0.3381	nM	ALDOSTERONE
9.44	Ki	0.36	nM	DEXAMETHASONE
9.41	Kd	0.39	nM	PROGESTERONE
9.40	Ki	0.4	nM	CHEMBL2181925
9.40	Ki	0.4	nM	CHEMBL4099276
9.33	EC50	0.47	nM	ALDOSTERONE
9.31	Ki	0.494	nM	CHEMBL235206
9.30	Kd	0.5	nM	CORTICOSTERONE
9.30	Kd	0.5	nM	HYDROCORTISONE
9.30	Kd	0.5	nM	ALDOSTERONE
9.30	Ki	0.5012	nM	CHEMBL4471322
9.27	Ki	0.54	nM	METRIBOLONE
9.22	EC50	0.6	nM	ALDOSTERONE
9.20	Ki	0.631	nM	CHEMBL4555842
9.19	Ki	0.64	nM	CHEMBL1672542
9.13	Kd	0.74	nM	CHEMBL97531
9.10	Ki	0.79	nM	CHEMBL4063735
9.10	Ki	0.7943	nM	CHEMBL4532472
9.10	IC50	0.7943	nM	CHEMBL4463240
9.02	Ki	0.967	nM	CHEMBL3120318
9.00	EC50	1	nM	CHEMBL4540313
8.92	IC50	1.2	nM	CHEMBL4087205
8.91	IC50	1.24	nM	STANOLONE
8.90	IC50	1.259	nM	CHEMBL196374
8.89	IC50	1.3	nM	CHEMBL4102708
8.89	EC50	1.3	nM	ALDOSTERONE
8.82	Ki	1.51	nM	CHEMBL391231
8.81	Ki	1.56	nM	CHEMBL235209
8.80	EC50	1.6	nM	CHEMBL4217175
8.80	IC50	1.6	nM	SPIRONOLACTONE
8.74	IC50	1.8	nM	CHEMBL3263752
8.70	Ki	2	nM	CHEMBL3578271
8.70	Ki	2	nM	CHEMBL3775752
8.70	IC50	2	nM	CHEMBL3775752
8.70	Ki	1.995	nM	CHEMBL4468672
8.70	IC50	2	nM	CHEMBL1215196
8.70	EC50	2	nM	PREDNISOLONE
8.68	Ki	2.1	nM	CHEMBL3605932
8.66	IC50	2.2	nM	CHEMBL3263768
8.65	Ki	2.25	nM	CHEMBL391231

PubChem BioAssay actives

1165 with measured affinity, of 2085 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Prednisolone	626803: Agonist activity at human mineralocorticoid receptor expressed in human A549 cells by fluorescence polarization assay	ec50	<0.0001	uM
[(3R)-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]methanesulfonamide	1623464: Modulation activity at human mineralocorticoid receptor in human EA.hy926 cells assessed as induction of nuclear translocation of mineralocorticoid receptor in absence of aldosterone by receptor translocation assay	ec50	0.0001	uM
[5-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1-(4-methylpiperazin-1-yl)benzimidazol-2-yl]cyanamide	1440445: Displacement of [3H]-Aldosterone from MR overexpressed in human 293 cells measured after 2 hrs by Microbeta scintillation counting method	ki	0.0001	uM
[1-[(7S,8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl]-5-[(E)-(3,7-difluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]benzimidazol-2-yl]cyanamide	1440445: Displacement of [3H]-Aldosterone from MR overexpressed in human 293 cells measured after 2 hrs by Microbeta scintillation counting method	ki	0.0002	uM
(8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde	1168715: Agonist activity at human MCR expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0002	uM
[(3R)-7-fluoro-6-(2-methylpropyl)-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]methanesulfonamide	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0003	uM
6-[(3R)-7-fluoro-3-(methylsulfonylmethyl)-2,3-dihydro-1,4-benzoxazine-4-carbonyl]-4H-1,4-benzoxazin-3-one	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0003	uM
N-[3-[(1S)-1-cyclopropyl-1-(2,4-difluorophenyl)ethyl]-1H-indol-7-yl]methanesulfonamide	570053: Displacement of [3H]methyltrienolone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0003	uM
N-[3-[(1E)-1-(6H-benzo[c][1]benzoxepin-11-ylidene)ethyl]phenyl]methanesulfonamide	1071639: Displacement of [3H]-aldosterone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0003	uM
[5-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1-[(2R)-1-morpholin-4-ylpropan-2-yl]benzimidazol-2-yl]urea	1440445: Displacement of [3H]-Aldosterone from MR overexpressed in human 293 cells measured after 2 hrs by Microbeta scintillation counting method	ki	0.0003	uM
Dexamethasone	1071639: Displacement of [3H]-aldosterone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0004	uM
[5-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1-[(2R)-1-morpholin-4-ylpropan-2-yl]benzimidazol-2-yl]cyanamide	1440445: Displacement of [3H]-Aldosterone from MR overexpressed in human 293 cells measured after 2 hrs by Microbeta scintillation counting method	ki	0.0004	uM
Progesterone	126283: Affinity for recombinant Mineralocorticoid receptor	kd	0.0004	uM
3-[(7S,8aS)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl]-6-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1H-benzimidazol-2-one	705920: Displacement of [3H]aldosterone from human mineralocorticoid receptor overexpressed in HEK293 cells by microbeta counting assay	ki	0.0004	uM
2-[(3S)-7-chloro-6-(2-methylpropyl)-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0005	uM
(8S,13S,14S,17S)-17-hydroxy-13,17-dimethyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[a]phenanthren-3-one	1276601: Displacement of [3H]-aldosterone from mineralocorticoid receptor (unknown origin) expressed in HEK293 cell lysate incubated overnight by microbeta scintillation counting method	ki	0.0005	uM
(8S,9S,10R,11S,13S,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one	1440431: Binding affinity to MR (unknown origin)	kd	0.0005	uM
hydrocortisone	1440431: Binding affinity to MR (unknown origin)	kd	0.0005	uM
2-[(3S)-7-fluoro-6-(2-methylpropyl)-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0006	uM
N-[3-[1-cyclopropyl-1-(4-fluorophenyl)ethyl]-1H-indol-7-yl]methanesulfonamide	570053: Displacement of [3H]methyltrienolone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0006	uM
17-(2-diazoacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one	126283: Affinity for recombinant Mineralocorticoid receptor	kd	0.0007	uM
[5-[(E)-(3,8-difluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1-[(2R)-1-morpholin-4-ylpropan-2-yl]benzimidazol-2-yl]cyanamide	1440445: Displacement of [3H]-Aldosterone from MR overexpressed in human 293 cells measured after 2 hrs by Microbeta scintillation counting method	ki	0.0008	uM
2-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	1623464: Modulation activity at human mineralocorticoid receptor in human EA.hy926 cells assessed as induction of nuclear translocation of mineralocorticoid receptor in absence of aldosterone by receptor translocation assay	ec50	0.0010	uM
N-[3-[(1E)-1-(6H-benzo[c][1]benzoxepin-11-ylidene)propyl]phenyl]methanesulfonamide	1071639: Displacement of [3H]-aldosterone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0010	uM
1-[4-chloro-2-(4-fluorophenyl)phenyl]-5-[(2S)-2-hydroxypropyl]-2-methyl-N-(4-methylsulfonylphenyl)pyrrole-3-carboxamide	1440424: Antagonist activity at Gal4-fused human MR LBD (671 to 984 residues) expressed in African Green Monkey CV-1 cells assessed as inhibition of aldosterone-induced transactivation activity after 20 hrs by luciferase reporter gene assay	ic50	0.0012	uM
4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide	516373: Binding affinity to human recombinant mineralocorticoid receptor expressed in baculovirus infected Sf9 cells	ic50	0.0013	uM
[3-methyl-4-[2-(8-methyl-3-oxo-4H-1,4-benzoxazin-6-yl)ethyl]phenyl] acetate	1440441: Antagonist activity at Gal4-fused human MR LBD (672 to 984 residues) expressed in HEK293T cells assessed as inhibition of aldosterone-induced transactivation activity after 24 hrs by luciferase reporter gene assay	ic50	0.0013	uM
N-[3-[(1R)-1-cyclopropyl-1-(2,4-difluorophenyl)ethyl]-1H-indol-7-yl]methanesulfonamide	570053: Displacement of [3H]methyltrienolone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0015	uM
N-[3-[(1R)-1-cyclopropyl-1-(4-fluorophenyl)ethyl]-1H-indol-7-yl]methanesulfonamide	304366: Binding affinity to human mineralocorticoid receptor	ki	0.0016	uM
Spironolactone	469719: Antagonist activity at mineralocorticoid receptor ligand binding domain expressed in african green monkey COS7 cells co-transfected with Gal4-LBD by luciferase reporter gene assay	ic50	0.0016	uM
(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6-[[4-[(4-hydroxyphenyl)sulfanylmethyl]phenyl]methyl]-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one	1375650: Induction of nuclear translocation of human recombinant ProLabel-tagged mineralocorticoid receptor expressed in CHO-K1 cells after 3 hrs by luminescence method	ec50	0.0016	uM
6-[(3R)-2-(4-cyano-3-methylphenyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-2-methoxypyridine-3-carboxylic acid	1140663: Binding affinity to mineralocorticoid receptor (unknown origin)	ic50	0.0018	uM
6-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-4H-1,4-benzoxazin-3-one	1284960: Antagonist activity against 6xHis-MBP-fused human MR LBD domain (732 to 984 amino acid residues) C808S mutant expressed in Escherichia coli BL21(DE3) assessed as inhibition of aldosterone-mediated receptor activation after 16 hrs by luciferase assay	ic50	0.0020	uM
6-[(3S)-7-fluoro-3-(2-methylpropyl)-2,3-dihydro-1,4-benzoxazine-4-carbonyl]-4H-1,4-benzoxazin-3-one	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0020	uM
4-[(3R)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-3-methoxybenzoic acid	499924: Antagonist activity at Gal4-tagged mineralocorticoid receptor expressed in human Huh7 cells by luciferase reporter gene assay	ic50	0.0020	uM
[3-methyl-4-[2-(3-oxo-4H-1,4-benzoxazin-6-yl)ethyl]phenyl] acetate	1440441: Antagonist activity at Gal4-fused human MR LBD (672 to 984 residues) expressed in HEK293T cells assessed as inhibition of aldosterone-induced transactivation activity after 24 hrs by luciferase reporter gene assay	ic50	0.0020	uM
(5R)-5-benzyl-5-(6-chloro-1H-benzimidazol-2-yl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-1,3-oxazolidine-2,4-dione	1226712: Binding affinity to mineralocorticoid receptor (unknown origin)	ki	0.0020	uM
N-[3-(3-chlorophenyl)-1H-indol-7-yl]methanesulfonamide	1240572: Displacement of [3H]-aldosterone from human mineralocorticoid receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay	ki	0.0021	uM
6-[(3R)-2-(4-cyano-3-methylphenyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-2-methoxy-N-(2H-tetrazol-5-yl)pyridine-3-carboxamide	1140664: Antagonist activity at mineralocorticoid receptor (unknown origin) by Gal4-based cellular assay	ic50	0.0022	uM
1-(2-hydroxyethyl)-4-methyl-N-(4-methylsulfonylphenyl)-5-[2-(trifluoromethyl)phenyl]pyrrole-3-carboxamide	705908: Antagonist activity at mineralocorticoid receptor	ic50	0.0024	uM
2-[(3S)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0025	uM
(1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one	1375650: Induction of nuclear translocation of human recombinant ProLabel-tagged mineralocorticoid receptor expressed in CHO-K1 cells after 3 hrs by luminescence method	ec50	0.0025	uM
N-[3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidenemethyl)phenyl]methanesulfonamide	1071639: Displacement of [3H]-aldosterone from human mineralocorticoid receptor expressed in HEK293 cells	ki	0.0025	uM
6-[(3R)-2-(4-cyano-3-methylphenyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-2-methoxypyridine-3-carboxamide	1140664: Antagonist activity at mineralocorticoid receptor (unknown origin) by Gal4-based cellular assay	ic50	0.0027	uM
6-[(3R)-2-(4-cyano-3-methylphenyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-2-methoxy-N-methylsulfonylpyridine-3-carboxamide	1140664: Antagonist activity at mineralocorticoid receptor (unknown origin) by Gal4-based cellular assay	ic50	0.0028	uM
1-[4-chloro-2-(trifluoromethyl)phenyl]-5-[(2S)-2-hydroxypropyl]-2-methyl-N-(4-methylsulfonylphenyl)pyrrole-3-carboxamide	1440424: Antagonist activity at Gal4-fused human MR LBD (671 to 984 residues) expressed in African Green Monkey CV-1 cells assessed as inhibition of aldosterone-induced transactivation activity after 20 hrs by luciferase reporter gene assay	ic50	0.0031	uM
2-[(3S)-6-cyclopropyl-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide	1623467: Displacement of [3H]-aldosterone to human mineralocorticoid receptor LBD by radiometric binding assay	ki	0.0032	uM
(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-[[4-(trifluoromethyl)phenyl]methyl]-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one	1375650: Induction of nuclear translocation of human recombinant ProLabel-tagged mineralocorticoid receptor expressed in CHO-K1 cells after 3 hrs by luminescence method	ec50	0.0032	uM
6-[(3R)-2-(5-cyano-6-methyl-2-pyridinyl)-3-cyclopentyl-3,4-dihydropyrazol-5-yl]-2-methoxy-N-methylpyridine-3-carboxamide	1140664: Antagonist activity at mineralocorticoid receptor (unknown origin) by Gal4-based cellular assay	ic50	0.0033	uM
1-[4-chloro-2-(trifluoromethyl)phenyl]-5-(2-hydroxyethyl)-2-methyl-N-(4-methylsulfonylphenyl)pyrrole-3-carboxamide	1440424: Antagonist activity at Gal4-fused human MR LBD (671 to 984 residues) expressed in African Green Monkey CV-1 cells assessed as inhibition of aldosterone-induced transactivation activity after 20 hrs by luciferase reporter gene assay	ic50	0.0037	uM

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aldosterone	affects localization, decreases reaction, increases activity, affects binding, affects ubiquitination (+2 more)	11
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	7
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Dexamethasone	increases activity, affects cotreatment, increases expression	3
Hydrocortisone	decreases abundance, increases activity, affects binding	3
Spironolactone	increases activity, affects ubiquitination, decreases reaction	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases reaction, increases activity	2
cypermethrin	increases activity, decreases expression, affects localization, decreases reaction	2
sodium arsenite	affects activity, decreases expression	2
fipronil	affects cotreatment, decreases expression, decreases reaction, increases activity	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Progesterone	affects cotreatment, decreases expression, increases reaction, increases expression, increases activity	2
8-Bromo Cyclic Adenosine Monophosphate	increases reaction, increases expression, affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
alachlor	affects localization, decreases reaction, increases activity	1
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
acephate	affects localization, decreases reaction, increases activity	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
3,4,3’,4’-tetrachloroazobenzene	affects binding	1
o,p’-DDT	affects localization, decreases reaction, increases activity	1
fenvalerate	decreases reaction, increases activity	1
cobaltous chloride	decreases expression	1
vinclozolin	affects binding, decreases activity	1
potassium chromate(VI)	decreases expression	1
prednylidene	increases activity	1
terbutylazine	affects localization, decreases reaction, increases activity	1

ChEMBL screening assays

286 unique, capped per target: 195 binding, 89 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022891	Functional	Antagonist activity at mineralocorticoid receptor in human A549 cells assessed as inhibition of 1.25 nM aldosterone-induced effect at 0.1 uM	Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators. — Bioorg Med Chem Lett
CHEMBL1060004	Binding	Binding affinity to MR by fluorescence polarization based competition binding assay	Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists. — Bioorg Med Chem Lett
CHEMBL4151836	ADMET	Agonist activity at human MR expressed in CHO-K1 cells assessed as increase in protein interaction between MR and its coactivator SRC at 5 uM incubated for 24 hrs by beta-galactosidase based chemiluminescence assay	Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101). — J Med Chem

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Z1	Abcam HeLa NR3C2 KO	Cancer cell line	Female
CVCL_B7YM	Abcam Raji NR3C2 KO	Cancer cell line	Male
CVCL_B9ZC	Abcam THP-1 NR3C2 KO	Cancer cell line	Male
CVCL_C7B1	Abcam PC-3 NR3C2 KO	Cancer cell line	Male
CVCL_E7IU	UG5LN GAL4-hMR	Cancer cell line	Female
CVCL_KY44	PathHunter CHO-K1 MR Protein Interaction	Spontaneously immortalized cell line	Female
CVCL_LF47	GeneBLAzer MR-UAS-bla HEK 293T	Transformed cell line	Female
CVCL_TB01	HAP1 NR3C2 (-) 1	Cancer cell line	Male
CVCL_TB02	HAP1 NR3C2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder