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NR1D1 Gene

protein-coding   GIFtS: 66
GCID: GC17M038249

Nuclear Receptor Subfamily 1, Group D, Member 1


(Previous symbol: THRAL)
  See related diseases
at  

(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 1, Group D, Member 11 2     hRev2
THRAL1 2 3 5     Nuclear Receptor Rev-ErbA-Alpha2
EAR12 3 5     Nuclear Receptor Subfamily 1 Group D Member 12
V-ErbA-Related Protein 12 3     rev-erbA-alpha2
Rev-ErbAalpha2     EAR-13
THRA12     HREV3
ear-12     Rev-erbA-alpha3

External Ids:    HGNC: 79621   Entrez Gene: 95722   Ensembl: ENSG000001263687   OMIM: 6024085   UniProtKB: P203933   

Export aliases for NR1D1 gene to outside databases

Previous GC identifers: GC17M037844 GC17P040302 GC17M038159 GC17M038624 GC17M035502 GC17M034042


(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 NR1D1 Gene:
This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein
is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In
particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear
translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in
metabolic, inflammatory and cardiovascular processes. (provided by RefSeq, Jan 2013)

GeneCards Summary for NR1D1 Gene:
NR1D1 (nuclear receptor subfamily 1, group D, member 1) is a protein-coding gene. Diseases associated with NR1D1 include cauda equina syndrome, and sleep disorder. GO annotations related to this gene include sequence-specific DNA binding and transcription regulatory region DNA binding. An important paralog of this gene is VDR.

UniProtKB/Swiss-Prot: NR1D1_HUMAN, P20393
Function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent
manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a
critical negative limb of the circadian clock by directly repressing the expression of core clock components
BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid
metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme
which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression.
Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as
either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response
element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE),
or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent
competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the
expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the
expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs);
represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic
expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via
repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in
pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion
and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by
increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of
CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy;
controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling
pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the
expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in
macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian
regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose
tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and
depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for
photoreceptor development and function. In addition to its activity as a repressor, can also act as a
transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays
a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent
manner

Gene Wiki entry for NR1D1 (Rev-ErbA alpha) 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_000017.11  NC_018928.2  NT_010783.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the NR1D1 gene promoter:
         Nkx3-1   Nkx3-1 v4   Nkx3-1 v1   LCR-F1   YY1   Arnt   Nkx3-1 v2   PPAR-gamma1   Ik-2   Nkx3-1 v3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNR1D1 promoter sequence
   Search Chromatin IP Primers for NR1D1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NR1D1


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

Entrez Gene cytogenetic band: 17q11.2   Ensembl cytogenetic band:  17q21.1   HGNC cytogenetic band: 17q11.2

NR1D1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NR1D1 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M038249:  view genomic region     (about GC identifiers)

Start:
38,249,037 bp from pter      End:
38,256,978 bp from pter
Size:
7,942 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, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NR1D1_HUMAN, P20393 (See protein sequence)
Recommended Name: Nuclear receptor subfamily 1 group D member 1  
Size: 614 amino acids; 66805 Da
Subunit: Binds DNA as a monomer or a homodimer. Interacts with C1D, NR2E3 and SP1 (By similarity). Interacts with
OPHN1 (via C-terminus). Interacts with ZNHIT1
5 PDB 3D structures from and Proteopedia for NR1D1:
1A6Y (3D)        1EF6 (3D)        1GA5 (3D)        1HLZ (3D)        3N00 (3D)    
Secondary accessions: Q0P5Z4 Q15304

Explore the universe of human proteins at neXtProt for NR1D1: NX_P20393

Explore proteomics data for NR1D1 at MOPED

Post-translational modifications: 

  • Ubiquitinated, leading to its proteasomal degradation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See NR1D1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_068370.1  
    ENSEMBL proteins: 
     ENSP00000246672  
    Reactome Protein details: P20393

    NR1D1 Human Recombinant Protein Products:

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    NR1D1 Antibody Products:

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    NR1D1 Assay Products:

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    Cloud-Clone Corp. ELISAs for NR1D1
    Cloud-Clone Corp. CLIAs for NR1D1


    (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: Rev-Erb-alpha
    1D. Rev-Erb receptors

    5 InterPro protein domains:
     IPR013088 Znf_NHR/GATA
     IPR008946 Nucl_hormone_rcpt_ligand-bd
     IPR000536 Nucl_hrmn_rcpt_lig-bd_core
     IPR001628 Znf_hrmn_rcpt
     IPR001723 Str_hrmn_rcpt

    Graphical View of Domain Structure for InterPro Entry P20393

    ProtoNet protein and cluster: P20393

    2 Blocks protein domains:
    IPB000324 Vitamin D receptor signature
    IPB001723 Steroid hormone receptor signature


    UniProtKB/Swiss-Prot: NR1D1_HUMAN, P20393
    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. NR1 subfamily
    Similarity: Contains 1 nuclear receptor DNA-binding domain


    NR1D1 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.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NR1D1_HUMAN, P20393
    Function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent
    manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a
    critical negative limb of the circadian clock by directly repressing the expression of core clock components
    BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid
    metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme
    which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression.
    Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as
    either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response
    element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE),
    or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent
    competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the
    expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the
    expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs);
    represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic
    expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via
    repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in
    pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion
    and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by
    increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of
    CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy;
    controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling
    pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the
    expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in
    macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian
    regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose
    tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and
    depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for
    photoreceptor development and function. In addition to its activity as a repressor, can also act as a
    transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays
    a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent
    manner

         Genatlas biochemistry entry for NR1D1:
    nuclear receptor subfamily 1,group D,member 1,partially overlapping THRA (exon for THRA2) on the opposite strand

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001046core promoter sequence-specific DNA binding IDA15761026
    GO:0001222transcription corepressor binding IMP18006707
    GO:0003677DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity ----
    GO:0003707steroid hormone receptor activity IEA--
         
    NR1D1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for NR1D1:
     Upregulation of Wnt/beta-caten 

         10 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Nr1d1):
     behavior/neurological  cellular  growth/size/body  homeostasis/metabolism  liver/biliary system 
     mortality/aging  muscle  nervous system  no phenotypic analysis  reproductive system 

    NR1D1 for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NR1D1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NR1D1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NR1D1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NR1D1

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  GTAGGTCACTGGGTCA 

    miRNA
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    miRTarBase miRNAs that target NR1D1:
    hsa-mir-335-5p (MIRT017335)

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    Selected qRT-PCR Assays for microRNAs that regulate NR1D1 (see all 9):
    hsa-miR-1290 hsa-miR-1266 hsa-miR-876-5p hsa-miR-3672 hsa-miR-29b-1* hsa-miR-4267 hsa-miR-3167 hsa-miR-338-5p
    SwitchGear 3'UTR luciferase reporter plasmidNR1D1 3' UTR sequence
    Inhib. RNA
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    Sino Biological Human cDNA Clone for NR1D1
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    (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
    NR1D1_HUMAN, P20393: Nucleus. Cytoplasm (By similarity). Cell projection, dendrite (By similarity). Cell
    projection, dendritic spine (By similarity). Note=Localizes to the cytoplasm, dendrites and dendritic spine in
    the presence of OPHN1 (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus4

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000790nuclear chromatin IDA18511497
    GO:0005634nucleus ISS--
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm ISS--
    GO:0030425dendrite ISS--

    NR1D1 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 NR1D1 About   (see all 10)  
    See pathways by source

    SuperPathContained pathways About
    1Circadian rhythm
    Circadian rhythm0.31
    Circadian Clock in Mammals0.31
    2Fatty acid, triacylglycerol, and ketone body metabolism
    Fatty acid, triacylglycerol, and ketone body metabolism0.65
    PPARA Activates Gene Expression0.63
    Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)0.65
    3Circadian Repression of Expression by REV-ERBA
    Circadian Repression of Expression by REV-ERBA0.88
    RORA Activates Circadian Expression0.88
    4Circadian Clock
    Circadian Clock0.66
    BMAL1-CLOCK/NPAS2 Activates Circadian Expression0.66
    5Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for NR1D1
        Circadian Clock in Mammals

    2 Cell Signaling Technology (CST) Pathways for NR1D1
        Glucose / Energy Metabolism
    NF-kappaB Signaling

    1 BioSystems Pathway for NR1D1
        Circadian rhythm pathway


    Selected Reactome Pathways for NR1D1 (see all 7)
        Circadian Clock
    Nuclear Receptor transcription pathway
    PPARA activates gene expression
    Transcriptional activation of mitochondrial biogenesis
    REV-ERBA represses gene expression


    1 Kegg Pathway  (Kegg details for NR1D1):
        Circadian rhythm


    NR1D1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NR1D1: 
              Circadian Rhythms in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NR1D1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for NR1D1 (P203933 ENSP000002466724) via UniProtKB, MINT, STRING, and/or I2D (see all 68)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NR1D2Q149953, ENSP000003100064I2D: score=2 STRING: ENSP00000310006
    NCOR1O753763, ENSP000002687124I2D: score=3 STRING: ENSP00000268712
    HDAC3O153793, ENSP000003029674I2D: score=1 STRING: ENSP00000302967
    HUWE1Q7Z6Z73, ENSP000002628544I2D: score=1 STRING: ENSP00000262854
    MYCBP2O755923, ENSP000003498924I2D: score=1 STRING: ENSP00000349892
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IMP18511497
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--
    GO:0007623circadian rhythm ----
    GO:0010467gene expression TAS--

    NR1D1 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 Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NR1D1

    3 IUPHAR Ligands for NR1D1 (Rev-Erb-alpha)    About this table
    LigandTypeActionAffinityPubmed IDs
    SR8278
    AntagonistAntagonist6.521043485
    GSK4112
    AgonistAgonist6.421043485
    heme
    AgonistAgonist6.418006707 18037887

    1 PharmGKB related drug/compound annotation for NR1D1 gene    About this table
    Drug/compound PharmGKB Annotation
    lithiumCA  



    NR1D1 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,
    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 NR1D1 gene: 
    NM_021724.4  

    Unigene Cluster for NR1D1:

    Nuclear receptor subfamily 1, group D, member 1
    Hs.592130  [show with all ESTs]
    Unigene Representative Sequence: NM_021724
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000246672(uc002htz.2 uc010cwq.2 uc010cwr.1)
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      QuantiTect SYBR Green Assays in human, mouse, rat NR1D1
      QuantiFast Probe-based Assays in human, mouse, rat NR1D1

    Additional mRNA sequence: 

    AK300155.1 AK315270.1 AY429554.1 BC047875.1 BC056148.1 HQ692861.1 M24898.1 X72631.1 

    14 DOTS entries:

    DT.99939115  DT.87015529  DT.118299  DT.95103779  DT.100031090  DT.118297  DT.97847061  DT.75124373 
    DT.100807968  DT.120980021  DT.120980162  DT.102833248  DT.120980143  DT.99953623 

    Selected AceView cDNA sequences (see all 146):

    BM709734 CR598991 BU956435 AA453202 BG747927 BC056148 CA425802 BU956398 
    M34340 BQ652234 BQ917541 BQ927499 BQ899181 CR608219 CN479067 CD630883 
    BM710421 BQ688463 BQ687824 BM662383 BM671861 BQ181923 R84761 BU150289 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for NR1D1 (see all 6)    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9
    SP1:                                                                              
    SP2:                                                  -                           
    SP3:                                                                              
    SP4:                                                  -     -     -               
    SP5:                                                                              


    ECgene alternative splicing isoforms for NR1D1

    (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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    NR1D1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CATTCCGAGA
    NR1D1 Expression
    About this image


    NR1D1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Heart (Cardiovascular System)
             Mature Cardiac Fibroblasts Myocardium
     
     Ovary (Reproductive System)
             Mature Granulosa Cells Antral Follicle
     
     Fibroblasts
             Mature Cardiac Fibroblasts Myocardium
     
     Neurons
             Rod Precursor Cells Outer Nuclear Layer
     
     Eye (Sensory Organs)
             Rod Precursor Cells Outer Nuclear Layer
    NR1D1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NR1D1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.592130

    UniProtKB/Swiss-Prot: NR1D1_HUMAN, P20393
    Tissue specificity: Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and
    brain. Also expressed in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and macrophages.
    Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral
    tissues. Expression increases during the differentiation of pre-adipocytes into mature adipocytes. Expressed at
    high levels in some squamous carcinoma cell lines

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NR1D1: 
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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)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for NR1D1 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nr1d11 , 5 nuclear receptor subfamily 1, group D, member 11, 5 90.01(n)1
    95.44(a)1
      11 (62.66 cM)5
    2171661  NM_145434.31  NP_663409.21 
     987679325 
    chicken
    (Gallus gallus)
    Aves --
    Uncharacterized protein
    30(a)
    many ↔ many
    28(2133083-2139829)
    lizard
    (Anolis carolinensis)
    Reptilia NR1D16
    nuclear receptor subfamily 1, group D, member 1
    71(a)
    1 ↔ 1
    6(69322211-69338166)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.97782 Xenopus laevis transcribed sequence with moderate similarity more 78.9(n)    BX847857.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.271242 Danio rerio nuclear receptor subfamily 1, group D, more 78.2(n)    AY391444.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Eip78C3 larval/pupal development (sensu
    Insecta) ligand-dependent more
    71(a)
    (best of 2)
        --
    worm
    (Caenorhabditis elegans)
    Secernentea sex-16
    nhr-856
    Protein NHR-85, isoform a
    24(a)
    24(a)
    many ↔ many
    many ↔ many
    X(10201328-10205433) WBGene00004786
    I(13056091-13062122) WBGene00003675


    ENSEMBL Gene Tree for NR1D1 (if available)
    TreeFam Gene Tree for NR1D1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NR1D1 gene
    VDR2  PPARD2  RARG2  NR1I22  PPARA2  THRB2  RARA2  NR1H42  
    NR1D22  RARB2  RORA2  RORB2  RORC2  NR1I32  PPARG2  NR1H22  
    THRA2  NR1H32  
    2 SIMAP similar genes for NR1D1 using alignment to 2 protein entries:     NR1D1_HUMAN (see all proteins):
    NR1D2    RORA

    NR1D1 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for NR1D1
    PGOHUM00000240883


    (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 NR1D1 (see all 334)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2008978671,2
    C--34049004(+) GGGGGA/GGGGGG 1 -- int10--------
    rs1889920921,2
    --38250732(+) AAGCAA/GCAGGA 1 -- int10--------
    rs1920544401,2
    --38250750(+) AGCCCC/TTTTCA 1 -- int10--------
    rs1834437041,2
    --38250765(+) TCAGGC/TTATAA 1 -- int10--------
    rs777981901,2
    C,F--38250766(+) CAGGCT/AATAAG 1 -- int11Minor allele frequency- A:0.02WA 118
    rs47948261,2
    C,F,H--38250782(-) ACCCAG/ATATCT 1 -- int112Minor allele frequency- A:0.05NS EA NA 1466
    rs1866328841,2
    --38250971(+) CATGGC/TGAAAC 1 -- int10--------
    rs1409236491,2
    C,F--38251177(+) ATAAAC/TGGTCA 1 -- int11Minor allele frequency- T:0.02EU 1311
    rs1997107601,2
    C--38251248(+) AAGCCC/TGGGAT 2 P syn10--------
    rs1424017471,2
    C,F--38251287(+) ACAGCG/AGGCGT 2 /P syn12Minor allele frequency- A:0.00NA EU 5873

    HapMap Linkage Disequilibrium report for NR1D1 (38249037 - 38256978 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for NR1D1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv908221CNV Loss21882294
    nsv520636CNV Loss19592680
    nsv528369CNV Loss19592680
    nsv833444CNV Loss17160897

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602408    OMIM disorders: --

    14 diseases for NR1D1:    
    About MalaCards
    cauda equina syndrome    sleep disorder    bipolar i disorder    schizoaffective disorder
    septic shock    major depressive disorder    anxiety disorder    mood disorder
    bipolar disorder    osteoarthritis    schizophrenia    thyroiditis
    tuberculosis    breast cancer


    NR1D1 for disorders           About GeneDecksing

    Genetic Association Database (GAD): NR1D1
    Human Genome Epidemiology (HuGE) Navigator: NR1D1 (15 documents)

    Export disorders for NR1D1 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 NR1D1 gene, integrated from 10 sources (see all 73):
    (articles sorted by number of sources associating them with NR1D1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. (PubMed id 1971514)1, 2, 3 Lazar M.A.... Chin W.W. (DNA Cell Biol. 1990)
    2. Association analysis of nuclear receptor Rev-erb alpha gene (NR1D1) with mood disorders in the Japanese population. (PubMed id 18804497)1, 4, 9 Kishi T....Iwata N. (Neurosci. Res. 2008)
    3. Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBalpha gene, a critical component of the circadian clock system. (PubMed id 19267705)1, 4, 9 Severino G....Del Zompo M. (Bipolar Disord 2009)
    4. Direct regulation of CLOCK expression by REV-ERB. (PubMed id 21479263)1, 2 Crumbley C. and Burris T.P. (PLoS ONE 2011)
    5. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. (PubMed id 20072116)1, 4 Soria V....Urretavizcaya M. (Neuropsychopharmacology 2010)
    6. Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. (PubMed id 20174623)1, 4 Utge S.J....Paunio T. (PLoS ONE 2010)
    7. Nuclear receptor rev-erb-{alpha} circadian gene variants and lithium carbonate prophylaxis in bipolar affective disorder. (PubMed id 20348464)1, 4 Campos-de-Sousa S....Collier D. (J. Biol. Rhythms 2010)
    8. PER2 variantion is associated with depression vulnerability. (PubMed id 19693801)1, 4 Lavebratt C....Forsell Y. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010)
    9. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    10. Interacting genes in lithium prophylaxis: preliminary results of an exploratory analysis on the role of DGKH and NR1D1 gene polymorphisms in 199 Sardinian bipolar patients. (PubMed id 19818381)1, 4 Manchia M....Del Zompo M. (Neurosci. Lett. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    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: 9572 HGNC: 7962 AceView: NR1D1 Ensembl:ENSG00000126368 euGenes: HUgn9572
    ECgene: NR1D1 Kegg: 9572 H-InvDB: NR1D1

    (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 NR1D1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NR1D1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NR1D1 gene:
    Search GeneIP for patents involving NR1D1

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



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