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NR3C2 Gene

protein-coding   GIFtS: 65
GCID: GC04M148999

Nuclear Receptor Subfamily 3, Group C, Member 2


(Previous symbol: MLR)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Nuclear Receptor Subfamily 3, Group C, Member 21 2     Aldosterone Receptor2
MLR1 2 3 5     Mineralocorticoid Receptor2
MCR2 3 5     Mineralocorticoid Receptor 12
MR2 3     Mineralocorticoid Receptor Delta2
NR3C2VIT2     Nuclear Receptor Subfamily 3 Group C Member 23

External Ids:    HGNC: 79791   Entrez Gene: 43062   Ensembl: ENSG000001516237   OMIM: 6009835   UniProtKB: P082353   

Export aliases for NR3C2 gene to outside databases

Previous GC identifers: GC04M149808 GC04M149375 GC04M149577 GC04M149357 GC04M149219 GC04M144727


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NR3C2 Gene:
This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance
within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to
mineralocorticoid response elements in order to transactivate target genes. Mutations in this gene cause
autosomal dominant pseudohypoaldosteronism type I, a disorder characterized by urinary salt wasting. Defects in
this gene are also associated with early onset hypertension with severe exacerbation in pregnancy. Alternative
splicing results in multiple transcript variants. (provided by RefSeq, Oct 2009)

GeneCards Summary for NR3C2 Gene:
NR3C2 (nuclear receptor subfamily 3, group C, member 2) is a protein-coding gene. Diseases associated with NR3C2 include autosomal dominant pseudohypoaldosteronism type 1, and hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy. GO annotations related to this gene include steroid hormone receptor activity and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is NR4A3.

UniProtKB/Swiss-Prot: MCR_HUMAN, P08235
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

summary for NR3C2 Gene:
Mineralocorticoid receptors (MRs) are nuclear hormone receptors of the NR3C class, which also includes
androgen, progesterone and glucocorticoid receptors. They can exist as homo- or heterodimers and are coupled
to Hsp90 or HMGB proteins. The major signaling pathway used by MRs is via direct DNA binding and
transcriptional regulation of target genes. They can also signal by binding to other proteins, mainly with
transcription factors such as NF-kappaB, AP-1 or STAT. MRs are expressed in epithelial tissues such as the
distal nephron and colon, and in non-epithelial tissues such as hippocampal and hypothalamic neurons.
Mineralocorticoid receptors are unique in that they have two physiological ligands; aldosterone and
cortisol, that act as critical regulators of serum sodium and other electrolytes and cardiovascular tone.
The human gene encoding the mineralocorticoid receptor has been localized to 4q31.1.

Gene Wiki entry for NR3C2 (Mineralocorticoid receptor) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000004.12  NT_016354.20  NC_018915.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NR3C2 gene promoter:
         TBP   AP-1   ATF-2   CUTL1   PPAR-gamma1   TFIID   PPAR-gamma2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): NR3C2 promoter sequence
   Search Chromatin IP Primers for NR3C2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NR3C2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q31.1   Ensembl cytogenetic band:  4q31.23   HGNC cytogenetic band: 4q31

NR3C2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NR3C2 gene location

GeneLoc information about chromosome 4         GeneLoc Exon Structure

GeneLoc location for GC04M148999:  view genomic region     (about GC identifiers)

Start:
148,999,913 bp from pter      End:
149,365,850 bp from pter
Size:
365,938 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: MCR_HUMAN, P08235 (See protein sequence)
Recommended Name: Mineralocorticoid receptor  
Size: 984 amino acids; 107067 Da
Subunit: 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
Selected PDB 3D structures from and Proteopedia for NR3C2 (see all 15):
1Y9R (3D)        1YA3 (3D)        2A3I (3D)        2AA2 (3D)        2AA5 (3D)        2AA6 (3D)    
Secondary accessions: B0ZBF5 Q2NKL1 Q96KQ8 Q96KQ9
Alternative splicing: 4 isoforms:  P08235-1   P08235-2   P08235-3   P08235-4   (Lacks steroid-binding activity and acts as ligand-independent transactivator)

Explore the universe of human proteins at neXtProt for NR3C2: NX_P08235

Explore proteomics data for NR3C2 at MOPED

Post-translational modifications: 

  • Phosphorylated1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See NR3C2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000892.2  NP_001159576.1  

    ENSEMBL proteins: 
     ENSP00000341390   ENSP00000350815   ENSP00000423510   ENSP00000343907   ENSP00000421481  
     ENSP00000347441  

    NR3C2 Human Recombinant Protein Products:

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    Browse Proteins at Cloud-Clone Corp.

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    NR: Nuclear hormone receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: Mineralocorticoid receptor
    3C. 3-Ketosteroid receptors

    4 InterPro protein domains:
     IPR013088 Znf_NHR/GATA
     IPR008946 Nucl_hormone_rcpt_ligand-bd
     IPR000536 Nucl_hrmn_rcpt_lig-bd_core
     IPR001628 Znf_hrmn_rcpt

    Graphical View of Domain Structure for InterPro Entry P08235

    ProtoNet protein and cluster: P08235

    1 Blocks protein domain: IPB000324 Vitamin D receptor signature

    UniProtKB/Swiss-Prot: MCR_HUMAN, P08235
    Domain: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal
    ligand-binding domain
    Similarity: Belongs to the nuclear hormone receptor family. NR3 subfamily
    Similarity: Contains 1 nuclear receptor DNA-binding domain


    NR3C2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MCR_HUMAN, P08235
    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

         Genatlas biochemistry entry for NR3C2:
    nuclear recptor subafamily 3,group C,member 1,steroid/thyroid hormone receptor superfamily

         Gene Ontology (GO): Selected molecular function terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003700sequence-specific DNA binding transcription factor activity IEA--
    GO:0003707steroid hormone receptor activity IEA--
    GO:0005496steroid binding IEA--
    GO:0005515protein binding IPI11518808
    GO:0008270zinc ion binding IEA--
         
    NR3C2 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for NR3C2:
     Increased cell death HMECs cel  Increased cell death in breast 

         10 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Nr3c2):
     behavior/neurological  cardiovascular system  cellular  growth/size/body  hematopoietic system 
     homeostasis/metabolism  mortality/aging  muscle  nervous system  renal/urinary system 

    NR3C2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Nr3c2tm2.1Gsc for NR3C2

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NR3C2
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NR3C2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NR3C2

    miRNA
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    miRTarBase miRNAs that target NR3C2:
    hsa-mir-135a-5p (MIRT001167), hsa-mir-19b-3p (MIRT001164), hsa-mir-335-5p (MIRT017785), hsa-mir-124-3p (MIRT001168), hsa-mir-148b-3p (MIRT019372)

    Block miRNA regulation of human, mouse, rat NR3C2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NR3C2 (see all 77):
    hsa-miR-548j hsa-miR-3607-3p hsa-miR-4272 hsa-miR-30d hsa-miR-30a hsa-miR-3613-3p hsa-miR-548a-5p hsa-miR-130b
    SwitchGear 3'UTR luciferase reporter plasmidNR3C2 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat NR3C2

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 2): NR3C2 (NM_000901)
    Sino Biological Human cDNA Clone for NR3C2
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NR3C2

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NR3C2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MCR_HUMAN, P08235: Cytoplasm. Nucleus. Endoplasmic reticulum membrane; Peripheral membrane protein.
    Note=Cytoplasmic and nuclear in the absence of ligand; nuclear after ligand-binding. When bound to HSD11B2, it is
    found associated with the endoplasmic reticulum membrane
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    nucleus5
    cytosol2
    extracellular2
    plasma membrane2
    cytoskeleton1
    mitochondrion1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ----
    GO:0005654nucleoplasm TAS--
    GO:0005789endoplasmic reticulum membrane IEA--
    GO:0043235receptor complex IDA--

    NR3C2 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NR3C2 About    
    See pathways by source

    SuperPathContained pathways About
    1Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
    Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics0.37
    ACE Inhibitor Pathway0.00
    ACE Inhibitor Pathway, Pharmacodynamics0.00
    2Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    3Nuclear Receptor transcription pathway
    Nuclear Receptor transcription pathway0.67
    4Aldosterone-regulated sodium reabsorption
    Aldosterone-regulated sodium reabsorption

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 BioSystems Pathway for NR3C2
        ACE Inhibitor Pathway


    2 PharmGKB Pathways for NR3C2
        ACE Inhibitor Pathway, Pharmacodynamics
    Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for NR3C2):
        Aldosterone-regulated sodium reabsorption


    NR3C2 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including NR3C2: 
              Nuclear Receptors & Coregulators in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NR3C2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 17)

    Selected Interacting proteins for NR3C2 (P082353 ENSP000003508154) via UniProtKB, MINT, STRING, and/or I2D (see all 25)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NR3C1P041503, ENSP000002315094I2D: score=3 STRING: ENSP00000231509
    FKBP4Q027903, ENSP000000010084I2D: score=2 STRING: ENSP00000001008
    PIAS1O759253, ENSP000002496364I2D: score=2 STRING: ENSP00000249636
    ARP102753, ENSP000003638224I2D: score=1 STRING: ENSP00000363822
    TRIM24O151643, ENSP000003405074I2D: score=2 STRING: ENSP00000340507
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006351transcription, DNA-templated ----
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--
    GO:0006883cellular sodium ion homeostasis ----
    GO:0007165signal transduction TAS3037703

    NR3C2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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      Browse compounds at ApexBio 

    Compounds for NR3C2 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CanrenoneMineralocorticoid receptor antagonist[976-71-6]
    RU 26752Mineralocorticoid receptor antagonist[76676-33-0]
    RU 28318, potassium salt Potent, selective mineralocorticoid receptor antagonist [76676-34-1]
    EplerenoneSelective mineralocorticoid receptor antagonist[107724-20-9]
    SpironolactoneMineralocorticoid receptor antagonist[52-01-7]

    6 HMDB Compounds for NR3C2    About this table
    CompoundSynonyms CAS #PubMed Ids
    Aldosterone(+)-Aldosterone (see all 22)52-39-117364595
    Cortexolone11-Deoxy-17-hydroxycorticosterone (see all 21)152-58-9--
    Corticosterone11,21-Dihydroxypregn-4-ene-3,20-dione (see all 8)50-22-6--
    Cortisol11-Hydrocortisone (see all 173)50-23-7--
    Deoxycorticosterone11-Dehydroxycorticosterone (see all 21)64-85-7--
    SodiumSodium (see all 2)7440-23-5--

    Selected DrugBank Compounds for NR3C2 (see all 11)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Spironolactone-- 52-01-7targetantagonist15128471 14664717 11791081 14978157 15808807 11752352 15947888 15554912
    Fludrocortisone-- 127-31-1targetagonist17666187 8733007 12198239 8157723 11752352 12888122
    Desoxycorticosterone PivalateDeoxycorticosterone Pivalate (see all 9)808-48-0targetagonist744157 17139284 11752352 17016423 6227474
    Drospirenone6β,7β,15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17 carbolactone (see all 4)67392-87-4targetantagonist8922878 11752352 11024226 8732994 7625729
    Eplerenone-- 107724-20-9targetantagonist14607457 11752352 15554912 14503934
    Aldosterone(+)-aldosterone (see all 18)52-39-1target--17724138 9392437 10592235
    Fluticasone Propionate-- 80474-14-2targetantagonist16507850 12503693
    (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE-- --target--10592235
    FelodipineDl-Felodipine (see all 4)72509-76-3targetantagonist18250364
    NimodipineNimodipino [INN-Spanish] (see all 2)66085-59-4targetantagonist18250364

    Selected IUPHAR Ligands for NR3C2 (Mineralocorticoid receptor) (see all 12)    About this table
    LigandTypeActionAffinityPubmed IDs
    progesterone
    AgonistAgonist118282004
    deoxycorticosterone
    AgonistAgonist118282004
    aldosterone
    AgonistAgonist9.8 - 108282004 10611474
    cortisol
    AgonistAgonist9.8 - 9.958282004 10611474
    fludrocortisone
    AgonistAgonist9.928282004
    dexamethasone
    AgonistAgonist98282004 10611474
    drospirenone
    AntagonistAntagonist1 - 51493716
    spironolactone
    AntagonistAntagonist12949071
    eplerenone
    AntagonistAntagonist12949071 16101407
    onapristone
    AntagonistAntagonist1--

    Selected Novoseek inferred chemical compound relationships for NR3C2 gene (see all 103)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    11beta-hydroxysteroid 95.4 200 7743156 (3), 7777721 (2), 8136102 (2), 7600648 (2) (see all 99)
    spironolactone 93.9 231 1313229 (5), 15554912 (5), 14664717 (4), 17569793 (4) (see all 99)
    eplerenone 93.7 101 15554912 (7), 16101407 (3), 10760075 (2), 19804189 (2) (see all 54)
    cortisone 91.3 78 11350956 (2), 12538613 (2), 11306334 (1), 15643127 (1) (see all 62)
    potassium canrenoate 86.4 12 9710353 (1), 15472204 (1), 17602195 (1), 8115025 (1) (see all 10)
    ru 26752 85.4 4 12657604 (1), 1314085 (1), 15716462 (1)
    11-dehydrocorticosterone 85.3 14 12711009 (3), 7777721 (1), 1734933 (1), 7988441 (1) (see all 8)
    tetrahydrocortisone 84.9 1 12944030 (1)
    carbenoxolone 82.1 15 7962269 (2), 9182864 (2), 1958552 (1), 15862816 (1) (see all 12)
    11,19-oxidoprogesterone 81.2 10 10860927 (3), 11909639 (2), 18001136 (2)



    NR3C2 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for NR3C2 gene (2 alternative transcripts): 
    NM_000901.4  NM_001166104.1  

    Unigene Cluster for NR3C2:

    Nuclear receptor subfamily 3, group C, member 2
    Hs.163924  [show with all ESTs]
    Unigene Representative Sequence: NM_000901
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000344721 ENST00000358102 ENST00000512865 ENST00000342437 ENST00000511528
    ENST00000503313 ENST00000503174 ENST00000504753 ENST00000355292(uc003ilj.4 uc003ilk.4 uc010iph.3)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Block miRNA regulation of human, mouse, rat NR3C2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NR3C2 (see all 77):
    hsa-miR-548j hsa-miR-3607-3p hsa-miR-4272 hsa-miR-30d hsa-miR-30a hsa-miR-3613-3p hsa-miR-548a-5p hsa-miR-130b
    SwitchGear 3'UTR luciferase reporter plasmidNR3C2 3' UTR sequence
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    OriGene RNAi products in human, mouse, rat for NR3C2
    Predesigned siRNA for gene silencing in human, mouse, rat NR3C2
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    GenScript: all cDNA clones in your preferred vector (see all 2): NR3C2 (NM_000901)
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    Additional mRNA sequence: 

    AB209056.1 AJ315515.1 AK123047.1 AK304318.1 BC111758.1 M16801.1 

    8 DOTS entries:

    DT.413476  DT.100774246  DT.101974427  DT.121250027  DT.121250041  DT.91756804  DT.97774369  DT.121249981 

    Selected AceView cDNA sequences (see all 80):

    BM830782 BM676581 BM823641 BQ892596 BM819064 AJ315514 BM714196 BM968064 
    BU608557 AJ315515 CD370581 BM830693 BQ083864 BQ187633 CB159499 CK429233 
    AA568349 NM_000901 M16801 W24096 BU187996 BM819087 AL041328 BF433882 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NR3C2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    NR3C2 Expression
    About this image


    NR3C2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Brain (Nervous System)    fully expand to see all 5 entries
             Cerebral Cortex
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Eye (Sensory Organs)
             GABAergic Amacrine Cells Inner Nuclear Layer
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
    NR3C2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NR3C2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.163924

    UniProtKB/Swiss-Prot: MCR_HUMAN, P08235
    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

        Pathway & Disease-focused RT2 Profiler PCR Array including NR3C2: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for NR3C2 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nr3c21 , 5 nuclear receptor subfamily 3, group C, member 21, 5 86.5(n)1
    90.71(a)1
      8 (36.34 cM)5
    1107841  NM_001083906.11  NP_001077375.11 
     768994425 
    chicken
    (Gallus gallus)
    Aves NR3C21 nuclear receptor subfamily 3, group C, member 2 77.97(n)
    82.94(a)
      374131  NM_001159345.1  NP_001152817.1 
    lizard
    (Anolis carolinensis)
    Reptilia NR3C26
    nuclear receptor subfamily 3, group C, member 2
    80(a)
    1 ↔ 1
    5(133739994-133913452)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.9702 Xenopus laevis mineralocorticoid receptor mRNA, partial more 79.73(n)    U15133.1 
    zebrafish
    (Danio rerio)
    Actinopterygii nr3c21 nuclear receptor subfamily 3, group C, member 2 58.54(n)
    54.22(a)
      562171  NM_001100403.1  NP_001093873.1 


    ENSEMBL Gene Tree for NR3C2 (if available)
    TreeFam Gene Tree for NR3C2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NR3C2 gene
    NR4A32  ESRRA2  NR4A12  PGR2  ESR22  NR3C12  AR2  NR4A22  
    ESRRB2  ESR12  ESRRG2  
    Selected SIMAP similar genes for NR3C2 using alignment to 5 protein entries:     MCR_HUMAN (see all proteins) (see all similar genes):
    ESRRB    ERRgamma    ESRRG    NR1H3    NR1I1    NR1I2
    NR5A2    NR1H2    AR    NR1F2    NR1F3    NR2F6
    RORA    RORB    RORC    NR6A1    ESR2    NR1A2

    NR3C2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NR3C2 (see all 7763)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 4 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs415113441,2,,4
    CEarly-onset hypertension with severe exacerbation in pregnancy (EOHSEP)4 pathogenic1148859806(-) TCTATC/TATCAT 4 S L mis12Minor allele frequency- T:0.00NA 4
    VAR_0312794
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312792 L P mis40--------
    VAR_0312694
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312692 C S mis40--------
    VAR_0312724
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312722 L P mis40--------
    VAR_0312684
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312682 G R mis40--------
    VAR_0156274
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0156272 L P mis40--------
    VAR_0312754
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312752 S P mis40--------
    VAR_0312764
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312762 S R mis40--------
    VAR_0360634
    A colorectal cancer sample4--see VAR_0360632 H Q mis40--------
    VAR_0312784
    Pseudohypoaldosteronism 1, autosomal dominant (PHA1A)4--see VAR_0312782 E G mis40--------

    HapMap Linkage Disequilibrium report for NR3C2 (148999913 - 149249913 bp, first 250kb of NR3C2)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NR3C2 (see all 13):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2197125CNV Deletion18987734
    esv2666114CNV Deletion23128226
    esv2728509CNV Deletion23290073
    esv2728510CNV Deletion23290073
    esv1084601CNV Insertion17803354
    nsv4541CNV Insertion18451855
    nsv293429CNV Loss16902084
    nsv880245CNV Loss21882294
    esv25663CNV Loss19812545
    nsv880246CNV Loss21882294

    Human Gene Mutation Database (HGMD): NR3C2
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing NR3C2
    DNA2.0 Custom Variant and Variant Library Synthesis for NR3C2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600983   
    OMIM disorders: 177735  605115  
    UniProtKB/Swiss-Prot: MCR_HUMAN, P08235
  • 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.
    Note=The disease is caused by mutations 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. Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • Selected diseases for NR3C2 (see all 81):    
    About MalaCards
    autosomal dominant pseudohypoaldosteronism type 1    hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy    apparent mineralocorticoid excess syndrome    pseudohypoaldosteronism
    nephrosclerosis    pseudohypoaldosteronism type 1    hypertension    anuria
    glucocorticoid-remediable aldosteronism    hypertensive heart disease    low renin hypertension    liddle syndrome
    conn's syndrome    systolic heart failure    acth deficiency    hyperaldosteronism
    gynecomastia    hypokalemia    glucocorticoid resistance    anxiety disorder

    7 diseases from the University of Copenhagen DISEASES database for NR3C2:
    Hypertension     Conn's syndrome     Hyperaldosteronism     Kidney disease
    Apparent mineralocorticoid excess syndrome     Hypokalemia     Heart disease

    NR3C2 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for NR3C2 gene (see all 92)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pseudohypoaldosteronism 91.1 37 20453518 (3), 7883835 (2), 17287415 (2), 12788847 (2) (see all 25)
    hyperaldosteronism 82.3 10 19443576 (1), 7804754 (1), 11353578 (1), 17683282 (1) (see all 9)
    aldosteronism primary 79.8 9 15808808 (1), 18594273 (1), 16823578 (1), 19356005 (1) (see all 9)
    liddles syndrome 79.1 10 12715144 (2), 15980941 (1), 11740142 (1), 12959913 (1) (see all 8)
    mineralocorticoid hypertension 78.7 4 12715144 (1), 9238855 (1), 12852254 (1)
    hypokalemia 73.6 22 10760070 (1), 17314322 (1), 11446888 (1), 15761540 (1) (see all 16)
    glucocorticoid-remediable aldosteronism 73.4 4 11740142 (1), 12715144 (1), 12959913 (1)
    hyperkalemia 69.4 9 15016134 (2), 16503757 (1), 19347366 (1), 20093814 (1) (see all 6)
    essential hypertension 66.2 17 8116017 (2), 18387084 (1), 14608520 (1), 19804189 (1) (see all 11)
    adrenal hyperplasia 59.9 2 18552288 (1), 15808809 (1)

    Genetic Association Database (GAD): NR3C2
    Human Genome Epidemiology (HuGE) Navigator: NR3C2 (35 documents)

    Export disorders for NR3C2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NR3C2 gene, integrated from 10 sources (see all 953):
    (articles sorted by number of sources associating them with NR3C2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. (PubMed id 9392437)1, 2, 7, 9 Bruner K.L.... Litwack G. (Recept. Signal Transduct. 1997)
    2. The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. (PubMed id 11350956)1, 2, 9 Odermatt A.... Frey F.J. (J. Biol. Chem. 2001)
    3. Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. (PubMed id 16954160)1, 2, 9 Riepe F.G.... Krone N. (J. Clin. Endocrinol. Metab. 2006)
    4. Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone. (PubMed id 19665310)1, 4, 9 van Leeuwen N....WA1st S. (Psychoneuroendocrinology 2010)
    5. Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor. (PubMed id 16061183)1, 2, 9 Li Y.... Xu H.E. (Mol. Cell 2005)
    6. Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism. (PubMed id 12483305)1, 2, 9 Arai K....Shibasaki T. (Hum. Genet. 2003)
    7. A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action. (PubMed id 11518808)1, 2, 9 Zennaro M.-C.... Lombes M. (Mol. Endocrinol. 2001)
    8. Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1. (PubMed id 17287415)1, 4, 9 Balsamo A....Riepe F.G. (Eur. J. Endocrinol. 2007)
    9. Association of aldosterone concentration and mineralocorticoid receptor genotype with potassium response to spironolactone in patients with heart failure. (PubMed id 20030467)1, 4, 9 Cavallari L.H....Stamos T.D. (Pharmacotherapy 2010)
    10. Association of a mineralocorticoid receptor gene polymorphism with hypertension in a Spanish population. (PubMed id 19325532)1, 4, 9 Martinez F....Chaves F.J. (Am. J. Hypertens. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4306 HGNC: 7979 AceView: NR3C2 Ensembl:ENSG00000151623 euGenes: HUgn4306
    ECgene: NR3C2 Kegg: 4306 H-InvDB: NR3C2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for NR3C2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NR3C2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=NR3C2[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/Mineralocorticoid_receptor

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NR3C2 gene:
    Search GeneIP for patents involving NR3C2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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