Affinage

NR3C2

Mineralocorticoid receptor · UniProt P08235

Round 2 corrected
Length
984 aa
Mass
107.1 kDa
Annotated
2026-04-29
130 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR3C2 encodes the mineralocorticoid receptor (MR), a ligand-activated nuclear receptor that binds aldosterone and glucocorticoids with high affinity and translocates to the nucleus to regulate target gene transcription, functioning in renal sodium homeostasis, cardiovascular physiology, HPA-axis feedback, and tumor suppression (PMID:3037703, PMID:9662404, PMID:15939817). Receptor activation depends on a ligand-mediated hydrogen bond network involving Asn770 and Thr945 in the ligand-binding domain and is gated by inhibitory phosphorylation at Ser843, which prevents ligand binding and is dynamically regulated by angiotensin II and WNK4 signaling to produce context-dependent responses in renal intercalated cells (PMID:15967794, PMID:24206662). In the collecting duct, MR cell-autonomously controls ENaC abundance and apical targeting for sodium reabsorption; in vascular endothelial and smooth muscle cells, MR mediates aldosterone-dependent ICAM1 upregulation and proinflammatory gene programs (PMID:26898302, PMID:18467630, PMID:15718497). Heterozygous loss-of-function NR3C2 mutations cause autosomal dominant pseudohypoaldosteronism type I, whereas the gain-of-function S810L mutation converts progesterone into an MR agonist and causes pregnancy-exacerbated hypertension (PMID:9662404, PMID:10884226).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1987 High

    Cloning of NR3C2 established the mineralocorticoid receptor as a member of the nuclear receptor superfamily that binds both aldosterone and glucocorticoids with high affinity and activates transcription, resolving the molecular identity of the aldosterone effector.

    Evidence cDNA cloning by low-stringency hybridization with GR probe; radioligand binding and reporter gene assays in expression systems

    PMID:3037703

    Open questions at the time
    • Endogenous target genes uncharacterized
    • Tissue-specific cofactor requirements unknown
    • Post-translational regulation not addressed
  2. 1998 High

    Identification of heterozygous loss-of-function NR3C2 mutations in pseudohypoaldosteronism type I kindreds proved that MR haploinsufficiency is sufficient to disrupt renal sodium balance, linking the receptor directly to human disease.

    Evidence Genetic linkage and mutation screening in multiple PHA1 kindreds; frameshift, nonsense, and splice-site mutations segregating with phenotype

    PMID:9662404

    Open questions at the time
    • Genotype–phenotype severity correlation not systematically assessed
    • Compensatory mechanisms in heterozygous tissue undefined
  3. 2000 High

    Structural and biochemical characterization of the S810L mutation revealed how a single residue change converts MR antagonists (progesterone) into agonists, explaining pregnancy-exacerbated hypertension and establishing the helix 3–helix 5 interface as a critical determinant of ligand selectivity.

    Evidence X-ray crystallography of MR LBD, site-directed mutagenesis, transactivation and binding assays in a hypertensive kindred

    PMID:10884226

    Open questions at the time
    • Full-length MR structure not resolved
    • Cofactor interactions with mutant receptor unknown
  4. 2005 High

    Crystal structures of the wild-type MR LBD with agonists and antagonists defined the Asn770–Thr945 hydrogen bond network as the activation switch, while parallel in vivo studies in cardiac-specific MR-overexpressing mice and vascular cells established critical roles for MR in arrhythmogenesis and vascular inflammation.

    Evidence X-ray crystallography with mutagenesis; cardiac-specific MR transgenic mice with electrophysiology and spironolactone rescue; RT-PCR, reporter assays, and microarray in human vascular smooth muscle cells

    PMID:15718497 PMID:15939817 PMID:15967794

    Open questions at the time
    • Cardiac MR target ion channel genes not individually characterized
    • Vascular MR cofactors not identified
    • Structural basis of antagonist-bound state in full receptor context unclear
  5. 2006 High

    Functional characterization of additional PHA1-causing NR3C2 mutations mapped distinct mechanisms of receptor inactivation—loss of ligand binding, failure of nuclear translocation, and conformational disruption—building a structure–function map of critical MR residues.

    Evidence Aldosterone binding assays, reporter transactivation, fluorescence microscopy for nuclear translocation, limited proteolysis on six disease mutations

    PMID:16954160

    Open questions at the time
    • No crystal structures for these individual mutants
    • Dominant-negative effects versus haploinsufficiency not distinguished for all mutants
  6. 2006 High

    The I180V polymorphism demonstrated that MR can have ligand-selective functional variation (reduced cortisol but not aldosterone sensitivity), establishing MR as a physiological mediator of cortisol-dependent HPA-axis feedback in humans.

    Evidence In vitro transactivation with cortisol versus aldosterone; Trier Social Stress Test with salivary/plasma cortisol in genotyped human subjects

    PMID:17018659

    Open questions at the time
    • Brain-specific MR targets mediating stress feedback undefined
    • Sex-specific mechanisms not fully dissected
  7. 2008 High

    Demonstration that endothelial MR directly upregulates ICAM1 and promotes leukocyte adhesion provided a molecular mechanism for aldosterone-driven vascular inflammation, explaining clinical benefits of MR antagonism in cardiovascular disease.

    Evidence siRNA knockdown of MR in human coronary/aortic endothelial cells; ICAM1 expression and functional leukocyte adhesion assay with spironolactone blockade

    PMID:18467630

    Open questions at the time
    • Broader endothelial MR transcriptome not defined
    • In vivo endothelial-specific MR knockout not performed in this study
  8. 2013 High

    Discovery of Ser843 phosphorylation as an inhibitory gate on MR ligand binding revealed how the same receptor produces distinct physiological outputs in different cell types: dephosphorylation by angiotensin II/WNK4 selectively activates MR in intercalated cells during volume depletion.

    Evidence Phosphospecific antibodies, phosphomimetic/phospho-null mutant binding assays, mouse genetic models, immunofluorescence in kidney

    PMID:24206662

    Open questions at the time
    • Kinase responsible for Ser843 phosphorylation not identified
    • Whether Ser843 phosphorylation operates in non-renal tissues unknown
  9. 2016 High

    Mosaic MR-knockout mice proved that MR cell-autonomously controls ENaC expression and apical targeting in collecting duct cells but regulates NCC indirectly, resolving a long-standing question about direct versus systemic aldosterone signaling in the distal nephron.

    Evidence Mosaic MR-knockout mouse model with side-by-side comparison of MR+ and MR− cells; immunofluorescence and Western blot for ENaC, NCC, Na-K-ATPase under Na+ restriction

    PMID:26898302

    Open questions at the time
    • Downstream MR transcriptional targets controlling ENaC trafficking not identified
    • Systemic mediator linking MR to NCC regulation uncharacterized
  10. 2016 High

    Identification of NR3C2 as a miR-301b target suppressed by MIF in PDAC, with genetic validation in mouse models, established MR as a tumor suppressor that inhibits EMT when expressed—extending MR biology beyond classical epithelial electrolyte transport.

    Evidence miRNA target validation, NR3C2 overexpression/knockdown, EMT marker analysis, MIF-knockout genetically engineered mouse PDAC model

    PMID:27197190

    Open questions at the time
    • Direct MR transcriptional targets mediating EMT suppression in PDAC not defined
    • Whether MR ligands are required for tumor suppressor activity unclear
  11. 2022 Medium

    NR3C2 overexpression in colorectal and colon cancer models suppressed proliferation, glycolysis, and angiogenesis by downregulating HK2/LDHA and inhibiting AKT/ERK signaling, revealing specific metabolic and signaling pathways through which MR exerts tumor suppression.

    Evidence Lentiviral NR3C2 overexpression/knockdown in CRC cell lines; metabolic assays (glucose, lactate, ATP); Western blot for AMPK, AKT, ERK phosphorylation; VEGF ELISA and tube formation; pathway activator rescue

    PMID:35191517 PMID:36950803

    Open questions at the time
    • Whether MR requires aldosterone/ligand binding to suppress glycolysis is untested
    • In vivo tumor models not included in all studies
    • AP-1 interaction mechanism from PDAC studies not confirmed in CRC
  12. 2024 Medium

    NR3C2 was shown to interact with the AP-1 complex to transcriptionally repress HK1/HK2/LDHA in PDAC, providing a direct transcriptional mechanism for MR-mediated glycolysis suppression and linking the MIF/MAPK-ERK and NR3C2/AP-1 pathways as opposing regulators of tumor glucose metabolism.

    Evidence AP-1 co-immunoprecipitation/interaction studies, NR3C2 overexpression/knockdown with metabolic assays, MAPK-ERK inhibition, mouse PDAC models

    PMID:38629149

    Open questions at the time
    • Structural basis of MR–AP-1 interaction unknown
    • Whether this mechanism operates in non-pancreatic cancers untested
    • Ligand dependence of MR–AP-1 interaction not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the kinase that phosphorylates MR at Ser843, the full-length MR structure in complex with cofactors, whether MR tumor-suppressive functions require ligand activation, and the tissue-specific MR interactome that dictates divergent physiological outputs across kidney, heart, vasculature, and tumors.
  • Ser843 kinase identity unknown
  • Full-length MR structure unresolved
  • Ligand dependence of tumor suppressor activity untested
  • Tissue-specific cofactor complexes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0008289 lipid binding 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-382551 Transport of small molecules 3 GO:0140110 transcription regulator activity 1
Partners
AP-1ENACICAM1WNK4

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The human mineralocorticoid receptor (hMR/NR3C2) was cloned by low-stringency hybridization with the glucocorticoid receptor cDNA. Expression studies demonstrated that it encodes a 107-kDa polypeptide that binds aldosterone with high affinity, activates gene transcription in response to aldosterone, also binds glucocorticoids with high affinity, and can stimulate a glucocorticoid-responsive promoter, establishing functional kinship with the glucocorticoid receptor. cDNA cloning, radioligand binding assays, reporter gene transactivation in expression studies Science High 3037703
1998 Heterozygous loss-of-function mutations in NR3C2 (frameshift, premature stop, and splice-donor mutations) cause autosomal dominant pseudohypoaldosteronism type I (PHA1), demonstrating that haploinsufficiency of the mineralocorticoid receptor is sufficient to impair renal sodium reabsorption and blood pressure homeostasis in humans. Genetic linkage and mutation screening in PHA1 kindreds; mutations include frameshift, nonsense, and splice-site variants in NR3C2 Nature genetics High 9662404
2000 The S810L gain-of-function mutation in NR3C2 causes early-onset hypertension markedly exacerbated by pregnancy. Biochemical and structural studies showed this mutation confers constitutive receptor activity and altered ligand specificity: progesterone and other steroids lacking a 21-hydroxyl group, normally MR antagonists, become potent agonists. Structural analysis indicated the mutation creates a new van der Waals contact between helix 5 and helix 3, substituting for the normal 21-hydroxyl–helix 3 interaction required for wild-type activation. Mutation identification in hypertensive kindred; in vitro ligand binding and transactivation assays; X-ray crystallographic structural analysis; mutagenesis Science High 10884226
2005 Crystal structures of the NR3C2 ligand-binding domain bound to agonists and antagonists, combined with mutagenesis, revealed that maximal receptor activation requires a ligand-mediated hydrogen bond network involving Asn770 (which stabilizes the loop preceding the AF-2 helix and contacts the hormone) and Thr945 on helix 10. The naturally occurring S810L mutant was shown structurally to activate by stabilizing a helix 3/helix 5 interaction that bypasses this hydrogen bond network requirement. X-ray crystallography of MR LBD with multiple ligands; site-directed mutagenesis; transactivation assays The Journal of biological chemistry High 15967794
2005 Human coronary artery and aortic vascular smooth muscle cells express functional NR3C2 (MR) mRNA and protein. Endogenous vascular smooth muscle MR mediates aldosterone-dependent gene transcription that is blocked by spironolactone. Angiotensin II also activates MR-mediated gene transcription in these cells via AT1 receptor signaling. Aldosterone via MR upregulates genes involved in vascular fibrosis, inflammation, and calcification. RT-PCR, Western blot, reporter gene transactivation, microarray, pharmacological blockade (spironolactone, losartan), aldosterone synthase inhibition Circulation research High 15718497
2005 Cardiac-specific overexpression of human NR3C2 (MR) in transgenic mice causes ion channel remodeling, prolonged ventricular repolarization, and severe life-threatening ventricular arrhythmias. These effects were prevented by the MR antagonist spironolactone, establishing a direct causal role for cardiac MR signaling in arrhythmogenesis. Conditional transgenic mouse model with cardiac-specific MR overexpression; electrophysiology; pharmacological rescue with spironolactone Circulation High 15939817
2006 Molecular characterization of six NR3C2 mutations causing autosomal dominant PHA1 revealed distinct mechanisms: a frameshift mutation (c.2871dupC) abolished aldosterone binding and transactivation via major conformational change; two nonsense mutations produced truncated proteins; missense S818L prevented aldosterone binding, transactivation, and nuclear translocation; and missense E972G showed reduced ligand-binding affinity and only 9% of wild-type transcriptional activity. Fluorescence-labeled MR subcellular translocation assays and proteolysis experiments mapped critical residues for MR structure and function. Aldosterone binding assays, reporter gene transactivation assays, fluorescence microscopy for nuclear translocation, limited proteolysis, 3D structural modeling The Journal of clinical endocrinology and metabolism High 16954160
2006 The common NR3C2 polymorphism I180V (MR180V) causes a mild loss of function specifically for cortisol as ligand (higher EC50 for cortisol-driven transactivation) without affecting aldosterone-driven transactivation. In vivo, carriers of the 180V allele showed enhanced salivary and plasma cortisol and heart rate responses to psychosocial stress, consistent with reduced cortisol-mediated MR dampening of the HPA axis. In vitro transactivation assays with cortisol and aldosterone on MR180I vs. MR180V; human psychosocial stress challenge (Trier Social Stress Test); salivary and plasma cortisol measurements The Journal of clinical endocrinology and metabolism High 17018659
2007 Two novel NR3C2 mutations causing PHA1 in Italian patients—a nonsense mutation (Y134X) and a frameshift (2125delA)—were functionally characterized and showed complete absence of aldosterone binding and transactivation. These data extend the spectrum of loss-of-function NR3C2 mutations and identify functionally important regions of the mineralocorticoid receptor protein. NR3C2 gene sequencing, aldosterone binding assays, reporter gene transactivation assays, microsatellite analysis European journal of endocrinology Medium 17287415
2008 Human coronary artery and aortic endothelial cells express functional NR3C2 (MR) and the cortisol-inactivating enzyme 11βHSD2. Aldosterone activates endogenous EC MR to upregulate ICAM1 mRNA and protein expression; this was blocked by spironolactone and by siRNA knockdown of MR. Aldosterone-induced ICAM1 surface expression promoted leukocyte–endothelial adhesion, an effect inhibited by spironolactone and ICAM1 blocking antibody. RT-PCR, Western blot, reporter gene transactivation, siRNA knockdown, ELISA, cell adhesion assays, pharmacological blockade Circulation research High 18467630
2013 Phosphorylation of NR3C2 at Ser843 in the ligand-binding domain prevents ligand binding and receptor activation. In the kidney, MR-S843-P is found exclusively in intercalated cells of the distal nephron. Angiotensin II and WNK4 signaling decrease MR-S843-P levels during volume depletion, whereas hyperkalemia increases MR-S843-P. Dephosphorylation of MR-S843-P leads to aldosterone-dependent upregulation of the apical proton pump and Cl-/HCO3- exchangers in intercalated cells, revealing a phosphorylation-based mechanism that selectively gates MR activity to produce distinct homeostatic responses to volume depletion versus hyperkalemia. Phosphospecific antibodies, in vitro ligand-binding assays with phosphomimetic and phospho-null mutants, mouse genetic models, immunofluorescence, patch-clamp/electrophysiology Cell metabolism High 24206662
2016 MIF drives a signaling axis in pancreatic ductal adenocarcinoma (PDAC) by upregulating miR-301b, which directly targets and suppresses NR3C2. Loss of NR3C2 function promotes epithelial-to-mesenchymal transition and reduces sensitivity to gemcitabine. Genetic deletion of MIF in a genetically engineered mouse model disrupted the MIF–miR-301b–NR3C2 axis, reducing metastasis and prolonging survival, establishing NR3C2 as a tumor suppressor downstream of MIF in PDAC. miRNA target prediction and validation, NR3C2 overexpression/knockdown in cell lines, EMT marker analysis, gemcitabine sensitivity assay, genetically engineered mouse model of PDAC with MIF deletion, patient cohort correlation Cancer research High 27197190
2016 In mice with mosaic deletion of NR3C2 (~20% of renal tubule cells), MR is essential for ENaC abundance and apical targeting as well as Na+-K+-ATPase expression in collecting system cells, but is dispensable for NCC abundance, phosphorylation, and Na+-K+-ATPase regulation in the distal convoluted tubule—even under dietary Na+ restriction. This cell-autonomous comparison established that aldosterone regulates ENaC directly through MR in the collecting system but controls NCC indirectly through systemic mechanisms. Mosaic MR-knockout mouse model (MR/X mice); immunofluorescence; Western blot for transport protein abundance and phosphorylation; dietary Na+ restriction challenge Pflugers Archiv : European journal of physiology High 26898302
2017 miR-135b-5p directly targets the 3′UTR of NR3C2 and suppresses its expression in pancreatic cancer cells, thereby promoting cell migration, invasion, and EMT. Rescue experiments confirmed that NR3C2 mediates the pro-tumorigenic effects of miR-135b-5p. Transwell migration/invasion assays, EMT marker immunostaining and Western blot, GEO database analysis, target validation by luciferase reporter and rescue experiments Biomedicine & pharmacotherapy Medium 29196101
2018 miR-766 directly targets NR3C2 in hepatocellular carcinoma cells, suppressing its expression and thereby promoting HCC cell proliferation and metastasis in vitro and in vivo. Mechanistically, miR-766 regulation of NR3C2 affected the β-catenin signaling pathway. qRT-PCR, luciferase reporter assay, xenograft mouse model, Western blot, cell proliferation and invasion assays FASEB journal Medium 30130435
2021 miR-301b-3p directly targets NR3C2 in breast cancer cells, as confirmed by dual-luciferase reporter assay. Overexpression of miR-301b-3p promoted breast cancer cell proliferation, migration, and invasion, while NR3C2 was downregulated in breast cancer cell lines; rescue experiments demonstrated that NR3C2 mediates these effects of miR-301b-3p. Dual-luciferase reporter assay, CCK-8 proliferation assay, Transwell migration/invasion assay, Western blot, rescue experiments Journal of oncology Medium 33542733
2023 NR3C2 inhibits colorectal cancer cell proliferation and induces G2/M cell cycle arrest by suppressing glucose metabolism: NR3C2 overexpression decreased HK2 and LDHA expression, reducing lactate production, glucose consumption, and ATP production. NR3C2 overexpression also reduced AMPK phosphorylation, placing NR3C2 upstream of AMPK in the regulation of glycolysis in CRC cells. Lentiviral overexpression/knockdown, MTT assay, colony formation, flow cytometry (cell cycle), lactate/glucose/ATP measurement, Western blot for AMPK phosphorylation, HK2, LDHA Journal of cellular and molecular medicine Medium 36950803
2022 NR3C2 overexpression in colon cancer cells inhibits proliferation, colony formation, migration, invasion, and angiogenesis (reduced VEGF secretion and tube formation). Mechanistically, NR3C2 overexpression suppressed the AKT/ERK signaling pathway, and pathway activators rescued the NR3C2-driven inhibition, placing NR3C2 as an upstream suppressor of AKT/ERK in colon cancer. CCK-8 assay, colony formation, wound healing, Transwell invasion, ELISA for VEGF, tube formation assay, Western blot for AKT/ERK phosphorylation Molecular medicine reports Medium 35191517
2024 In PDAC, NR3C2 suppresses glycolytic metabolism by interacting with the activator protein 1 (AP-1) transcription factor complex to downregulate HK1, HK2, and LDHA expression, thereby inhibiting glucose uptake and lactate efflux. Conversely, MIF activates glycolysis through MAPK-ERK signaling. The MIF/NR3C2 axis thus dually regulates glucose metabolism reprogramming in pancreatic cancer. Gene expression analysis in PDAC patient cohorts, in vitro metabolic assays (glucose uptake, lactate efflux), NR3C2 overexpression/knockdown, Western blot for HK1/HK2/LDHA, MAPK-ERK pathway inhibition, AP-1 co-immunoprecipitation/interaction studies, mouse PDAC models Carcinogenesis Medium 38629149
2009 The NR3C2 promoter region SNP MR-2G/C (rs2070951) affects in vitro transactivational capacity of MR in response to cortisol or dexamethasone in a sex-specific manner. Female subjects homozygous for the G allele showed greatest suppression of the cortisol awakening response after dexamethasone administration, while male GG subjects showed attenuated suppression, implicating this functional MR variant in HPA-axis glucocorticoid feedback. SNP genotyping, in vitro MR transactivation assays, dexamethasone suppression test with cortisol awakening response measurement in human subjects Psychoneuroendocrinology Medium 19665310
2020 miR-454 directly targets NR3C2 in oral squamous cell carcinoma (OSCC) cells, as validated by GEO database expression analysis and co-transfection rescue experiments. Depletion of miR-454 decreased OSCC cell proliferation, colony formation, invasion, and migration, effects that were partially reversed by NR3C2 silencing, establishing NR3C2 as a functional downstream effector mediating miR-454's tumor-promoting activities. GEO database analysis, miR-454 mimic/inhibitor transfection, pcDNA3.1-NR3C2/si-NR3C2 co-transfection, cell proliferation, colony formation, Transwell assays Journal of oral pathology & medicine Low 32170966
2020 LINC01128 acts as a competing endogenous RNA (ceRNA) for miR-4260, thereby upregulating NR3C2 expression in AML cells. Inhibition of miR-4260 reduced AML cell proliferation and increased apoptosis; mechanistically, LINC01128 competed with NR3C2 for miR-4260 binding. Reduced levels of both LINC01128 and NR3C2 were identified in AML, and rescue assays confirmed that LINC01128 suppresses AML progression through the miR-4260/NR3C2 axis. miR-4260 inhibitor transfection, LINC01128 overexpression/knockdown, cell proliferation/apoptosis assays, luciferase reporter assay for ceRNA interactions, rescue experiments Cancer biology & therapy Low 32338183
2020 In pancreatic β-cells (INS-1), LINC-P21 acts as a ceRNA sponging miR-766-3p to upregulate NR3C2. Overexpression of NR3C2 inhibited INS-1 cell proliferation and glucose-stimulated insulin secretion, while NR3C2 knockdown had opposite effects, placing NR3C2 as a functional regulator of β-cell proliferation and insulin secretion downstream of the LINC-P21/miR-766-3p axis. CCK-8 proliferation assay, ELISA for insulin secretion, miR-766-3p mimic/inhibitor, NR3C2 overexpression/knockdown, luciferase reporter assay Experimental and clinical endocrinology & diabetes Low 33007789
2020 CREB1 binds the miR-1204 promoter and activates its transcription (ChIP assay). miR-1204 directly targets and inhibits NR3C2 (luciferase reporter assay and RIP). In glioblastoma cells, miR-1204 overexpression promoted proliferation and suppressed apoptosis (CCK-8, TUNEL), and rescue experiments confirmed that NR3C2 mediates these effects, identifying a CREB1–miR-1204–NR3C2 axis in GBM. ChIP assay for CREB1 at miR-1204 promoter, RIP assay, luciferase reporter assay, CCK-8, colony formation, caspase-3 activity, TUNEL, rescue experiments Cancer cell international Medium 32280303

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science (New York, N.Y.) 1752 3037703
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2017 Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science (New York, N.Y.) 934 28473536
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1999 Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nature genetics 769 10391210
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science (New York, N.Y.) 441 10884226
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2005 Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circulation research 296 15718497
1998 Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nature genetics 268 9662404
2016 A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2. Cancer research 256 27197190
2023 Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study. BMC psychiatry 240 37582716
2013 Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature genetics 240 23291589
2008 Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circulation research 231 18467630
1997 Paramagnetic metal scavenging by melanin: MR imaging. Radiology 229 9240529
2005 Cellular MR imaging. Molecular imaging 226 16194447
2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics 222 22589738
2005 Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation 213 15939817
2005 Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: a pilot study. Circulation 212 16275882
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2013 A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS genetics 190 23408906
2005 A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. The Journal of biological chemistry 165 15967794
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2011 MR imaging of parotid tumors: typical lesion characteristics in MR imaging improve discrimination between benign and malignant disease. AJNR. American journal of neuroradiology 157 21724574
2006 A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. The Journal of clinical endocrinology and metabolism 151 17018659
2013 Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia. Cell metabolism 150 24206662
2001 Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension (Dallas, Tex. : 1979) 149 11711524
1989 Cardiac masses: assessment by MR imaging. AJR. American journal of roentgenology 142 2783798
2007 Developing MR reporter genes: promises and pitfalls. NMR in biomedicine 139 17451181
2003 MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 127 12736767
2008 Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors. Antimicrobial agents and chemotherapy 101 18299405
2015 MR imaging probes: design and applications. Dalton transactions (Cambridge, England : 2003) 93 25376893
2002 Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience. Radiology 92 12355012
1997 Pancreatic neoplasms: MR imaging and pathologic correlation. Radiographics : a review publication of the Radiological Society of North America, Inc 92 9084072
1993 Herpesvirus infections of the CNS: MR findings. AJR. American journal of roentgenology 92 8390790
2022 The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality. Diagnostics (Basel, Switzerland) 89 35054289
2003 Nucleolytic processing of a protein-bound DNA end by the E. coli SbcCD (MR) complex. DNA repair 81 12826280
1987 Adrenoleukodystrophy: correlating MR imaging with CT. Radiology 80 3659373
1993 Cystic acoustic schwannomas: MR characteristics. AJNR. American journal of neuroradiology 76 8237710
2004 MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR. American journal of neuroradiology 73 15090362
2017 miR-135b-5p Promotes migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 70 29196101
1991 Subcortical and cortical components of the MLR generating system. Brain research 70 2039939
2009 Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone. Psychoneuroendocrinology 67 19665310
2017 Association of a Haplotype in the NR3C2 Gene, Encoding the Mineralocorticoid Receptor, With Chronic Central Serous Chorioretinopathy. JAMA ophthalmology 65 28334414
2007 CT and MR characteristics of cerebral sparganosis. AJNR. American journal of neuroradiology 64 17885230
1994 Orbital and optic pathway sarcoidosis: MR findings. AJNR. American journal of neuroradiology 64 8010282
2011 Distinguishing between germinomas and pineal cell tumors on MR imaging. AJNR. American journal of neuroradiology 63 22173760
2018 Quantitative MR Evaluation of Chronic Pancreatitis: Extracellular Volume Fraction and MR Relaxometry. AJR. American journal of roentgenology 60 29336598
2012 Pediatric liver MR elastography. Digestive diseases and sciences 59 22569825
2018 MicroRNA-766 promotes cancer progression by targeting NR3C2 in hepatocellular carcinoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 30130435
1987 The cardiac gap junction protein (Mr 47,000) has a tissue-specific cytoplasmic domain of Mr 17,000 at its carboxy-terminus. Biochemical and biophysical research communications 51 3028402
2011 Active and silent members in the mlr gene cluster of a microcystin-degrading bacterium isolated from Lake Taihu, China. FEMS microbiology letters 50 21676013
1992 Diagnosis of fatty liver with MR imaging. Journal of magnetic resonance imaging : JMRI 50 1633400
2016 The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. Pflugers Archiv : European journal of physiology 49 26898302
1986 Pineal germinoma: MR imaging. Radiology 48 3941869
2016 Presence or Absence of mlr Genes and Nutrient Concentrations Co-Determine the Microcystin Biodegradation Efficiency of a Natural Bacterial Community. Toxins 47 27827872
2019 Radiomics in Kidney Cancer: MR Imaging. Magnetic resonance imaging clinics of North America 46 30466904
1993 Meningiomas in children: MR and histopathologic findings. AJNR. American journal of neuroradiology 46 8427097
2024 Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). International journal of chronic obstructive pulmonary disease 44 38414718
2022 The Predictive Role of Maternal Biological Markers and Inflammatory Scores NLR, PLR, MLR, SII, and SIRI for the Risk of Preterm Delivery. Journal of clinical medicine 44 36498555
2006 Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. The Journal of clinical endocrinology and metabolism 44 16954160
1993 MION-ASF: biokinetics of an MR receptor agent. Magnetic resonance imaging 41 7685055
2001 Mechanisms of dendritic cell-induced T cell proliferation in the primary MLR assay. Immunology letters 40 11672590
1992 Perfusion and diffusion MR imaging. Magnetic resonance in medicine 40 1569868
1979 Specific inhibition of human lymphocyte responses by primed autologous lymphocytes. I. Evaluation of MLR inhibition as a model for suppression. Journal of immunology (Baltimore, Md. : 1950) 40 87456
1989 MR imaging of callosal and corticocallosal dysgenesis. AJNR. American journal of neuroradiology 39 2494854
1986 Sickle-cell nephropathy: MR imaging. Radiology 38 3941863
2010 NTM and NR3C2 polymorphisms influencing intelligence: family-based association studies. Progress in neuro-psychopharmacology & biological psychiatry 37 21036197
2021 Transcranial MR-Guided Histotripsy System. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 36 33755563
2021 Glucocorticoids: Dr. Jekyll and Mr. Hyde of Hippocampal Neuroinflammation. Biochemistry. Biokhimiia 36 33832414
2011 Integrin Targeted MR Imaging. Theranostics 36 21547154
2020 Source apportionment of water pollutants in the upstream of Yangtze River using APCS-MLR. Environmental geochemistry and health 35 32594417
2009 Catalytic antibodies: balancing between Dr. Jekyll and Mr. Hyde. BioEssays : news and reviews in molecular, cellular and developmental biology 35 19795406
2020 MR Imaging of SCA3/MJD. Frontiers in neuroscience 34 32848545
1999 Telomerase: Dr Jekyll or Mr Hyde? Current opinion in genetics & development 34 10377284
1999 Sodium and proton MR properties of cartilage during compression. Journal of magnetic resonance imaging : JMRI 33 10581509
1991 Experimental hepatocellular carcinoma: MR receptor imaging. Radiology 33 1871273
2020 Fast Imaging for Hyperpolarized MR Metabolic Imaging. Journal of magnetic resonance imaging : JMRI 31 32039520
2019 Knockdown of lncRNA Gm11974 protect against cerebral ischemic reperfusion through miR-766-3p/NR3C2 axis. Artificial cells, nanomedicine, and biotechnology 30 31556305
2018 MR approaches in neurodegenerative disorders. Progress in nuclear magnetic resonance spectroscopy 30 30538047
2015 Cardiac GR and MR: From Development to Pathology. Trends in endocrinology and metabolism: TEM 29 26586027
2012 MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. The Journal of pharmacology and experimental therapeutics 29 22473614
2021 miR-301b-3p Regulates Breast Cancer Cell Proliferation, Migration, and Invasion by Targeting NR3C2. Journal of oncology 28 33542733
1994 MLR-52, (4'-demethylamino-4',5'-dihydroxystaurosporine), a new inhibitor of protein kinase C with immunosuppressive activity. The Journal of antibiotics 28 7802863
2023 MR Elastography in Cancer. Investigative radiology 27 36897804
1997 Craniocerebral plasmacytoma: MR features. AJNR. American journal of neuroradiology 27 9111682
2020 Water quality assessment and pollution source apportionment using multi-statistic and APCS-MLR modeling techniques in Min River Basin, China. Environmental science and pollution research international 25 32705557
2011 Multipathway sequences for MR thermometry. Magnetic resonance in medicine 24 21394774
2020 Insights into ecological roles and potential evolution of Mlr-dependent microcystin-degrading bacteria. The Science of the total environment 23 31926423
1995 Juxtaglomerular cell tumor: MR findings. Journal of computer assisted tomography 23 7822532
2023 Molecular Engineering of Self-Immolative Bioresponsive MR Probes. Journal of the American Chemical Society 22 37116079
2020 Elevated microRNA-135b-5p relieves neuronal injury and inflammation in post-stroke cognitive impairment by targeting NR3C2. The International journal of neuroscience 22 32713242
2020 Application of APCA-MLR receptor model for source apportionment of char and soot in sediments. The Science of the total environment 22 32771758
2017 Detection of Stem Cell Transplant Rejection with Ferumoxytol MR Imaging: Correlation of MR Imaging Findings with Those at Intravital Microscopy. Radiology 22 28128708
1975 Possible use of established cell lines for MLR locus typing. Tissue antigens 22 124481
2013 TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane. Biochimica et biophysica acta 21 23500070
2005 Leg ischemia: assessment with MR angiography and spectroscopy. Radiology 21 15681685
1998 Adolescent case of Alexander disease: MR imaging and MR spectroscopy. Pediatric neurology 21 9492095
2023 NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK. Journal of cellular and molecular medicine 20 36950803
2022 NR3C2 suppresses the proliferation, migration, invasion and angiogenesis of colon cancer cells by inhibiting the AKT/ERK signaling pathway. Molecular medicine reports 20 35191517
2020 miR-454 performs tumor-promoting effects in oral squamous cell carcinoma via reducing NR3C2. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 20 32170966
2002 MR imaging and 1H-MR spectroscopy in a case of juvenile Alexander disease. Brain & development 20 12427522
2020 Clinical PET/MR. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 19 32594404
2013 Effect of NR3C2 genetic polymorphisms on the blood pressure response to enalapril treatment. Pharmacogenomics 18 24059494
2024 Monocytes Count, NLR, MLR and PLR in Canine Inflammatory Bowel Disease. Animals : an open access journal from MDPI 17 38539935
2021 Long noncoding RNA SOX2OT silencing alleviates cerebral ischemia-reperfusion injury via miR-135a-5p-mediated NR3C2 inhibition. Brain research bulletin 17 34022287
1999 MR 20492 and MR 20494: two indolizinone derivatives that strongly inhibit human aromatase. The Journal of steroid biochemistry and molecular biology 17 10529003
1996 MR of the submandibular gland: normal and pathologic states. AJNR. American journal of neuroradiology 17 8883659
1995 The action spectra for UV-induced suppression of MLR and MECLR show that immunosuppression is mediated by DNA damage. Photochemistry and photobiology 17 8570704
1981 Alloreactive T cells: expression of HLA-D antigens, stimulation of autologous MLR, and possible immunoregulatory function. Human immunology 17 6460016
2021 The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias. Frontiers in endocrinology 16 34262530
2021 Microglia replacement by microglia transplantation (Mr MT) in the adult mouse brain. STAR protocols 16 34308380
2020 CREB1-induced miR-1204 promoted malignant phenotype of glioblastoma through targeting NR3C2. Cancer cell international 16 32280303
2020 LINC01128 resisted acute myeloid leukemia through regulating miR-4260/NR3C2. Cancer biology & therapy 16 32338183
2020 Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic β-cell Function by Sponging miR-766-3p to Upregulate NR3C2. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 16 33007789
2013 Diffusion weighted MR imaging and proton MR spectroscopy findings of central neurocytoma with pathological correlation. Journal of neuroradiology = Journal de neuroradiologie 16 24238840
2007 Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1. European journal of endocrinology 16 17287415
2003 Intraoperative MR imaging. Magnetic resonance imaging clinics of North America 16 14768728
2024 MIF/NR3C2 axis regulates glucose metabolism reprogramming in pancreatic cancer through MAPK-ERK and AP-1 pathways. Carcinogenesis 15 38629149
2021 Real-time MR tracking of AAV gene therapy with βgal-responsive MR probe in a murine model of GM1-gangliosidosis. Molecular therapy. Methods & clinical development 15 34703836
2006 Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain. AJR. American journal of roentgenology 15 16928952
2020 Protein corona: Dr. Jekyll and Mr. Hyde of nanomedicine. Biotechnology and applied biochemistry 14 33007792