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LRP6 Gene

protein-coding   GIFtS: 68
GCID: GC12M012272

Low Density Lipoprotein Receptor-Related Protein 6

  See LRP6-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
Low Density Lipoprotein Receptor-Related Protein 61 2
LRP-62 3
ADCAD22 5
Low-Density Lipoprotein Receptor-Related Protein 62

External Ids:    HGNC: 66981   Entrez Gene: 40402   Ensembl: ENSG000000700187   OMIM: 6035075   UniProtKB: O755813   

Export aliases for LRP6 gene to outside databases

Previous GC identifers: GC12M012001 GC12M012417 GC12M012173 GC12M012164


(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 LRP6 Gene:
This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are
transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands.
The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby
transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin
signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration
and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated
intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been
determined.(provided by RefSeq, Dec 2009)

GeneCards Summary for LRP6 Gene:
LRP6 (low density lipoprotein receptor-related protein 6) is a protein-coding gene. Diseases associated with LRP6 include coronary artery disease, autosomal dominant, 2, and sost-related sclerosing bone dysplasia. GO annotations related to this gene include protein homodimerization activity and frizzled binding. An important paralog of this gene is LRP5.

UniProtKB/Swiss-Prot: LRP6_HUMAN, O75581
Function: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing
aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of
Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor
complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the
cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and
destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By
similarity)

Gene Wiki entry for LRP6 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 at NCBI GenBank:
NC_000012.11  NT_009714.18  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the LRP6 gene promoter:
         LHX3b/Lhx3b   MyoD   Nkx2-5   HNF-4alpha2   HNF-4alpha1   Egr-2   c-Myb   LHX3a/Lhx3a   Pax-4a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidLRP6 promoter sequence
   Search Chromatin IP Primers for LRP6

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat LRP6


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

Entrez Gene cytogenetic band: 12p13.2   Ensembl cytogenetic band:  12p13.2   HGNC cytogenetic band: 12p13.2

LRP6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
LRP6 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M012272:  view genomic region     (about GC identifiers)

Start:
12,268,959 bp from pter      End:
12,419,946 bp from pter
Size:
150,988 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, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, 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: LRP6_HUMAN, O75581 (See protein sequence)
Recommended Name: Low-density lipoprotein receptor-related protein 6 precursor  
Size: 1613 amino acids; 180429 Da
Subunit: Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Forms a
WNT-signaling complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the extracellular
domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the
beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B.
Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and
DRAXIN. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation.
Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling (By similarity).
Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to
cell surface LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively
regulating the Wnt signaling pathway (By similarity). Interacts (via the extracellular domain) with RSPO1; the
interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the
cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta-propeller
regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling.
Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma
membrane (By similarity). Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates
LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts with MACF1.
Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards
clathrin-mediated endocytosis. Interacts with TMEM198
Selected PDB 3D structures from and Proteopedia for LRP6 (see all 9):
3S2K (3D)        3S8V (3D)        3S8Z (3D)        3S94 (3D)        3SOB (3D)        3SOQ (3D)    
Secondary accessions: Q17RZ2

Explore the universe of human proteins at neXtProt for LRP6: NX_O75581

Explore proteomics data for LRP6 at MOPED

Post-translational modifications: 

  • Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by GSK3 and CK1 is required for AXIN1-binding, and
    subsequent stabilization and activation of beta-catenin via preventing GSK3-mediated phosphorylation of
    beta-catenin. Phosphorylated, in vitro, by GRK5/6 within and outside the PPPSP motifs. Phosphorylation at
    Ser-1490 by CDK14 during G2/M phase leads to regulation of the Wnt signaling pathway during the cell cycle.
    Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by casein
    kinase I on Thr-14791
  • Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first
    released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released
    into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling1
  • Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic
    reticulum1
  • Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its
    degradation by the proteasome1
  • N-glycosylation is required for cell surface location1
  • Ubiquitination2 at Lys1403
  • Glycosylation2 at Asn42, Asn81, Asn281, Asn433, Asn486, Asn692, Asn859, Asn865, Asn926, Asn1039
  • Modification sites at PhosphoSitePlus

  • See LRP6 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002327.2  
    ENSEMBL proteins: 
     ENSP00000261349   ENSP00000445083   ENSP00000443239   ENSP00000442472   ENSP00000439765  
    Reactome Protein details: O75581

    LRP6 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    OriGene Protein Over-expression Lysate for LRP6
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    Novus Biologicals LRP6 Lysate
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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for LRP6

     
    Search eBioscience for Proteins for LRP6 

    LRP6 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of LRP6
    R&D Systems Antibodies for LRP6 (LRP-6)
    Cell Signaling Technology (CST) Antibodies for LRP6 
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    OriGene Custom Antibody Services for LRP6
    Novus Biologicals LRP6 Antibodies
    Abcam antibodies for LRP6
    Cloud-Clone Corp. Antibodies for LRP6
    ThermoFisher Antibodies for LRP6
    LSBio Antibodies in human, mouse, rat for LRP6

    LRP6 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    R&D Systems Proteome Profiler Antibody Arrays for LRP6 (LRP-6)
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for LRP6
    Cloud-Clone Corp. CLIAs for LRP6
    Search eBioscience for ELISAs for LRP6 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    LDLR: Low density lipoprotein receptors

    Selected InterPro protein domains (see all 6):
     IPR002172 LDrepeatLR_classA_rpt
     IPR000033 LDLR_classB_rpt
     IPR023415 LDLR_class-A_CS
     IPR000742 EG-like_dom
     IPR011042 6-blade_b-propeller_TolB-like

    Graphical View of Domain Structure for InterPro Entry O75581

    ProtoNet protein and cluster: O75581

    1 Blocks protein domain: IPB002172 Low density lipoprotein-receptor

    UniProtKB/Swiss-Prot: LRP6_HUMAN, O75581
    Domain: The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The
    YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1
    Domain: The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate
    the Wnt signaling pathway
    Similarity: Belongs to the LDLR family
    Similarity: Contains 4 EGF-like domains
    Similarity: Contains 3 LDL-receptor class A domains
    Similarity: Contains 20 LDL-receptor class B repeats


    Find genes that share domains with LRP6           About GenesLikeMe


    (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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: LRP6_HUMAN, O75581
    Function: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing
    aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of
    Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor
    complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the
    cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and
    destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By
    similarity)
    Induction: Decreased levels on WNT3A stimulation

         Genatlas biochemistry entry for LRP6:
    low-density lipoprotein receptor related protein 6,putative tumor suppressor of leukemia

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005041low-density lipoprotein receptor activity IDA16263759
    GO:0005102receptor binding IPI14739301
    GO:0005109frizzled binding IPI11029007
    GO:0005515protein binding IPI11029007
    GO:0017147Wnt-protein binding IPI11029007
         
    Find genes that share ontologies with LRP6           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for LRP6:
     Decreased BPV1 E2 protein expr  Increased HPV18 LCR reporter a 

         Selected MGI mutant phenotypes (inferred from 10 alleles(MGI details for Lrp6) (see all 21):
     adipose tissue  behavior/neurological  cellular  craniofacial  digestive/alimentary 
     embryogenesis  growth/size/body  hearing/vestibular/ear  homeostasis/metabolism  integument 
     limbs/digits/tail  liver/biliary system  mortality/aging  nervous system  no phenotypic analysis 

    Find genes that share phenotypes with LRP6           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for LRP6: Lrp6tm1.2Vari Lrp6tm1.2Cjz

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for LRP6
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for LRP6

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for LRP6
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for LRP6

    miRNA
    Products:
        
    miRTarBase miRNAs that target LRP6:
    hsa-mir-92a-3p (MIRT049446), hsa-mir-221-3p (MIRT046906), hsa-mir-628-3p (MIRT039587), hsa-mir-940 (MIRT036618), hsa-mir-26a-5p (MIRT050127), hsa-mir-7-5p (MIRT025965), hsa-mir-335-5p (MIRT019112)

    Block miRNA regulation of human, mouse, rat LRP6 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate LRP6 (see all 136):
    hsa-miR-579 hsa-miR-3938 hsa-miR-128 hsa-miR-3653 hsa-miR-3921 hsa-miR-208b hsa-miR-130b hsa-miR-3612
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat LRP6

    Gene Editing
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    Clone
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    OriGene clones in human, mouse for LRP6 (see all 6)
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    GenScript: all cDNA clones in your preferred vector: LRP6 (NM_002336)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for LRP6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat LRP6
    Addgene plasmids for LRP6 

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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LRP6


    (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
    LRP6_HUMAN, O75581: Membrane; Single-pass type I membrane protein. Endoplasmic reticulum. Note=On Wnt signaling,
    undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the
    endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the
    absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at
    the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma membrane by MESD (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    plasma membrane4
    endosome2
    extracellular2
    nucleus2
    lysosome1

    Gene Ontology (GO): Selected cellular component terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005769colocalizes with early endosome IDA16890161
    GO:0005783endoplasmic reticulum IEA--
    GO:0005794colocalizes with Golgi apparatus IDA16890161
    GO:0005886plasma membrane IDA16263759
    GO:0005901colocalizes with caveola IDA16890161

    Find genes that share ontologies with LRP6           About GenesLikeMe


    (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 LRP6 About   (see all 11)  
    See pathways by source

    SuperPathContained pathways About
    1Wnt signaling pathway (KEGG)
    Wnt signaling pathway0.40
    Wnt Signaling Pathway NetPath0.37
    Wnt Signaling Pathways0.40
    2Wnt Signaling Pathway (WikiPathways)
    Wnt Signaling Pathway and Pluripotency0.55
    3ERK Signaling
    Molecular Mechanisms of Cancer0.51
    4Wnt signaling network
    Wnt signaling network
    5WNT Signaling
    WNT Signaling


    Find genes that share SuperPaths with LRP6           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for LRP6
        Wnt Signaling Pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for LRP6
        Molecular Mechanisms of Cancer
    Reelin Pathway (Cajal-Retzius cells)
    Colorectal Cancer Metastasis
    WNT Signaling

    1 Cell Signaling Technology (CST) Pathway for LRP6
        Wnt / Hedgehog / Notch

    Selected BioSystems Pathways for LRP6 (see all 6)
        MicroRNAs in cardiomyocyte hypertrophy
    Wnt Signaling Pathway and Pluripotency
    Wnt Signaling Pathway NetPath
    Wnt signaling network
    Canonical Wnt signaling pathway

    4 Reactome Pathways for LRP6
        regulation of FZD by ubiquitination
    disassembly of the destruction complex and recruitment of AXIN to the membrane
    negative regulation of TCF-dependent signaling by WNT ligand antagonists
    TCF dependent signaling in response to WNT


    1 Kegg Pathway  (Kegg details for LRP6):
        Wnt signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including LRP6: 
              WNT Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Alzheimer's Disease in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for LRP6

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

    Selected Interacting proteins for LRP6 (O755811, 2, 3 ENSP000002613494) via UniProtKB, MINT, STRING, and/or I2D (see all 63)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DAB2P980821, 2EBI-910915,EBI-1171238 MINT-8383369 MINT-8383520 MINT-8383467 MINT-8383354 MINT-8383493 MINT-8383480 MINT-8382936 MINT-8383325 MINT-8383417 MINT-8383507 MINT-8383533 MINT-8382947 MINT-8383280 MINT-8383454 MINT-8382960 MINT-8383399 MINT-8383303 MINT-8382978 MINT-8383384 MINT-8383339
    AMMECR1Q9Y4X01, 2EBI-910915,EBI-8583355 MINT-8183643 MINT-8183454 MINT-8183525 MINT-8183661 MINT-8183678 MINT-8183545
    ANTXR1Q9H6X21, 3, ENSP000003019454EBI-910915,EBI-905643 I2D: score=2 STRING: ENSP00000301945
    DKK1O949071, 3, ENSP000003630814EBI-910915,EBI-742864 I2D: score=2 STRING: ENSP00000363081
    CAV1Q031351, 3, ENSP000003391914EBI-910915,EBI-603614 I2D: score=1 STRING: ENSP00000339191
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 94):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001702gastrulation with mouth forming second IBA--
    GO:0001756somitogenesis ----
    GO:0001843neural tube closure IBA--
    GO:0001933negative regulation of protein phosphorylation IMP16365045
    GO:0001947heart looping IEA--

    Find genes that share ontologies with LRP6           About GenesLikeMe



    (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)
    About This Section

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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 LRP6

    3 Novoseek inferred chemical compound relationships for LRP6 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    glycogen 43.9 11 18077588 (1), 16341017 (1), 16890161 (1), 17326769 (1) (see all 9)
    cysteine 3.93 1 18378904 (1)
    tyrosine 0 2 17376403 (1), 18717822 (1)



    Find genes that share compounds with LRP6           About GenesLikeMe



    (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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for LRP6 gene: 
    NM_002336.2  

    Unigene Clusters for LRP6:

    Low density lipoprotein receptor-related protein 6
    Hs.584775  [show with all ESTs], Hs.658913  [show with all ESTs]
    Unigene Representative Sequences: NM_002336, AK094666
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000261349(uc001rah.4 uc010shl.1) ENST00000538239 ENST00000540527
    ENST00000543091 ENST00000540415 ENST00000545658 ENST00000535731
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate LRP6 (see all 136):
    hsa-miR-579 hsa-miR-3938 hsa-miR-128 hsa-miR-3653 hsa-miR-3921 hsa-miR-208b hsa-miR-130b hsa-miR-3612
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      QuantiFast Probe-based Assays in human, mouse, rat LRP6

    Additional mRNA sequence: 

    AK094666.1 BC029941.1 

    11 DOTS entries:

    DT.414150  DT.101981899  DT.92425465  DT.109958  DT.87046267  DT.100743801  DT.100754945  DT.40198822 
    DT.65287114  DT.95131613  DT.95362565 

    Selected AceView cDNA sequences (see all 161):

    CD678976 BM668604 AA130038 AI144434 AI768638 AA126365 AI926097 AI796948 
    AW510975 AI151494 BU628979 AK094666 AI140433 BU731128 AW376180 BM981464 
    AI765587 AA025391 BM694517 AI341834 AI277748 AA838728 AI580411 AF074264 

    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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    LRP6 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAATTAAATA
    LRP6 Expression
    About this image


    LRP6 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Thymus (Hematopoietic System)
             Thymus
     
     Primitive Streak (Early Embryonic Tissues)
             Primitive Streak Cells Primitive Streak
     
     Kidney (Urinary System)
             Metanephros
    LRP6 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    LRP6 Protein Expression

    SOURCE GeneReport for Unigene clusters: Hs.584775 Hs.658913

    UniProtKB/Swiss-Prot: LRP6_HUMAN, O75581
    Tissue specificity: Widely coexpressed with LRP5 during embryogenesis and in adult tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including LRP6: 
              WNT Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Alzheimer's Disease in human mouse rat

    Primer
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LRP6

    (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 animals.

    Orthologs for LRP6 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Lrp61 , 5 low density lipoprotein receptor-related protein 61, 5 90.91(n)1
    98.02(a)1
      6 (65.37 cM)5
    169741  NM_008514.41  NP_032540.21 
     1344464765 
    chicken
    (Gallus gallus)
    Aves LRP61 low density lipoprotein receptor-related protein 6 82.17(n)
    93.06(a)
      419097  XM_417286.4  XP_417286.3 
    lizard
    (Anolis carolinensis)
    Reptilia LRP66
    low density lipoprotein receptor-related protein 6...
    91(a)
    1 ↔ 1
    5(83061283-83142830)
    African clawed frog
    (Xenopus laevis)
    Amphibia lrp6-B2 lipoprotein receptor-related protein 6 76.93(n)    AF508961.1 
    zebrafish
    (Danio rerio)
    Actinopterygii lrp61 low-density lipoprotein receptor-related protein 6 69.39(n)
    81.53(a)
      100003877  NM_001134684.1  NP_001128156.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta arr1 , 3 Wnt receptor signaling pathway
    low-density lipoprotein receptor less3
    arrow1
    42(a)3
    50.58(n)1
    45.65(a)1
      442791  NM_079998.31  NP_524737.21 


    ENSEMBL Gene Tree for LRP6 (if available)
    TreeFam Gene Tree for LRP6 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for LRP6 gene
    LRP52  LRP22  LRP1B2  EGF2  LDLR2  LRP5L2  LRP42  VLDLR2  
    NID12  NID22  LRP82  LRP12  
    10 SIMAP similar genes for LRP6 using alignment to 6 protein entries:     LRP6_HUMAN (see all proteins):
    LRP5    LRP5L    LRP4    LRP1    CD320    LDLR
    LRP1B    LRP8    DIET1    VLDLR

    Find genes that share paralogs with LRP6           About GenesLikeMe



    (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 LRP6 (see all 3229)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0347014
    Coronary artery disease, autosomal dominant, 2 (ADCAD2)4--see VAR_0347012 R C mis40--------
    rs664971641,2
    C--12042261(+) TCTTAA/-AAAAA 1 -- int11Minor allele frequency- -:0.00NA 2
    rs714358941,2
    C--12068296(+) ATAGTATTATA/-
            
    ATCCC
    1 -- int11Minor allele frequency- -:0.50NA 2
    rs668003881,2
    C--12072426(+) CCAGT-/AATCCG 1 -- int10--------
    rs38415261,2
    C,F--12077526(+) CAAACTT/-ATATT 1 -- int12Minor allele frequency- -:0.50NA CSA 4
    rs777979291,2
    C--12077526(+) CAAACA/TTATAT 1 -- int10--------
    rs606425931,2
    C,F--12080117(+) CATTT-/G/GATT
            
    ATTAA
    1 -- int12NA CSA 6
    rs113128291,2
    C--12102526(+) AAAAA-/GCAAAA 1 -- int10--------
    rs562186061,2
    C--12102559(+) CAAAA-/AAA   
      A
    /CAAA
    CCAAT
    1 -- int10--------
    rs356416591,2
    C--12103973(+) TTTTT-/GT/TG 
            
    GTGTG
    1 -- int11NA 2

    HapMap Linkage Disequilibrium report for LRP6 (12268959 - 12419946 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for LRP6:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2745567CNV Deletion23290073
    esv2658217CNV Deletion23128226
    nsv832332CNV Loss17160897
    nsv529005CNV Loss19592680
    nsv898806CNV Gain21882294

    Human Gene Mutation Database (HGMD): LRP6
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing LRP6
    DNA2.0 Custom Variant and Variant Library Synthesis for LRP6

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 603507   
    OMIM disorders: 610947  
    UniProtKB/Swiss-Prot: LRP6_HUMAN, O75581
  • Coronary artery disease, autosomal dominant, 2 (ADCAD2) [MIM:610947]: A common heart disease
    characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart.
    Its most important complication is acute myocardial infarction. Note=The disease is caused by mutations affecting
    the gene represented in this entry

  • 4 diseases for LRP6:    
    About MalaCards
    coronary artery disease, autosomal dominant, 2    sost-related sclerosing bone dysplasia    artery disease    coronary artery disease

    2 diseases from the University of Copenhagen DISEASES database for LRP6:
    SOST-related sclerosing bone dysplasia     Osteoporosis

    Find genes that share disorders with LRP6           About GenesLikeMe

    7 Novoseek inferred disease relationships for LRP6 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    high bone mass 61.1 1 17002572 (1)
    anthrax 42.9 16 18350154 (5), 17335347 (4), 18717822 (3), 16564002 (2)
    osteoporosis 42 3 16355283 (1), 18493104 (1), 18349089 (1)
    cancer 13.8 6 15516984 (2), 17255260 (1), 20446724 (1), 19549913 (1) (see all 5)
    colorectal cancer 10.5 1 17255260 (1)
    breast cancer 2.19 11 20194742 (4), 19881541 (1)
    tumors 0 6 20194742 (2), 12827279 (1), 19549913 (1)

    Genetic Association Database (GAD): LRP6
    Human Genome Epidemiology (HuGE) Navigator: LRP6 (25 documents)

    Export disorders for LRP6 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 LRP6 gene, integrated from 10 sources (see all 198):
    (articles sorted by number of sources associating them with LRP6)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. (PubMed id 9704021)1, 2, 3, 9 Brown S.D.... Hess J.F. (Biochem. Biophys. Res. Commun. 1998)
    2. Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6. (PubMed id 18362152)1, 2, 9 MacDonald B.T.... He X. (J. Biol. Chem. 2008)
    3. Regulated proteolytic processing of LRP6 results in release of its intracellular domain. (PubMed id 17326769)1, 2, 9 Mi K. and Johnson G.V. (J. Neurochem. 2007)
    4. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. (PubMed id 17569865)1, 2, 9 Bilic J.... Niehrs C. (Science 2007)
    5. Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor. (PubMed id 17698587)1, 2, 9 Khan Z.... Bafico A. (Mol. Cell. Biol. 2007)
    6. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. (PubMed id 20093360)1, 2, 9 Bourhis E.... Hannoush R.N. (J. Biol. Chem. 2010)
    7. Lack of association of LRP5 and LRP6 polymorphisms with type 2 diabetes mellitus in the Japanese population. (PubMed id 18493104)1, 4, 9 Zenibayashi M....Kasuga M. (Endocr. J. 2008)
    8. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. (PubMed id 16513652)1, 2, 9 Swiatek W.... Virshup D.M. (J. Biol. Chem. 2006)
    9. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. (PubMed id 11448771)1, 2, 9 Semenov M.V.... He X. (Curr. Biol. 2001)
    10. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. (PubMed id 19293931)1, 2, 9 Wu G.... He X. (PLoS ONE 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: 4040 HGNC: 6698 AceView: LRP6 Ensembl:ENSG00000070018 euGenes: HUgn4040
    ECgene: LRP6 Kegg: 4040 H-InvDB: LRP6

    (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)
    About This Section

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    NameDescription
    PharmGKB entry for LRP6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for LRP6 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 LRP6 gene:
    Search GeneIP for patents involving LRP6

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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