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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

LRP6 Gene

protein-coding   GIFtS: 65
GCID: GC12M012173

low density lipoprotein receptor-related protein 6
 Explore 28 diseases affiliated with
LRP6 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for LRP6    

Aliases
for LRP6 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
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 GC12M012164


Summaries
for LRP6 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for LRP6:
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)

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000012.11  NC_018923.1  NT_009714.17  
Regulatory elements:
   SABiosciences 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 plasmid: LRP6 promoter sequence
   Search SABiosciences Chromatin IP Primers for LRP6

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 GC12M012173:  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

Proteins
for LRP6 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: 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)
6/9 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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_O75581

    • LRP6 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_002327.2  
    ENSEMBL proteins: 
     ENSP00000261349   ENSP00000445083   ENSP00000443239   ENSP00000442472   ENSP00000439765  

    Human Recombinant Protein Products: 
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    R&D Systems Recombinant & Natural Proteins for LRP6 (LRP-6)
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    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate: LRP6
    OriGene Custom Protein Services for LRP6 
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    Novus Biologicals LRP6 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for LRP6

    Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005624membrane fraction ----
    GO:0005769early endosome IEA--
    GO:0005783endoplasmic reticulum IEA--
    GO:0005886plasma membrane IDA17569865
    GO:0005901colocalizes with caveola IDA17569865


    LRP6 for ontologies           About GeneDecksing



    LRP6 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of LRP6
    R&D Systems Antibodies for LRP6 (LRP-6)
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    Novus Biologicals LRP6 Antibodies
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    Assay Products for LRP6: 
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    Uscn ELISAs and CLIAs for LRP6

    Protein Domains /
    Families
    for LRP6 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    LRP6 for domains           About GeneDecksing

    5/6 InterPro domains/families (see all 6):
     IPR000033 LDLR_classB_rpt
     IPR023415 LDLR_class-A_CS
     IPR000742 EG-like_dom
     IPR002172 LDrepeatLR_classA_rpt
     IPR011042 6-blade_b-propeller_TolB-like

    Graphical View of Domain Structure for InterPro Entry O75581

    ProtoNet protein and cluster: O75581

    1 Blocks protein family: 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


    Function
    for LRP6 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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)
    Induction: Decreased levels on WNT3A stimulation

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

    miRNA
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat LRP6
    8/136 QIAGEN miScript miRNA 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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    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for LRP6 (see all 7)
    OriGene shRNA RFP: LRP6
    OriGene siRNA: LRP6
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat LRP6

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for LRP6

    Clone
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    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for LRP6 (see all 3)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat LRP6 

    Cell Line
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    Search LifeMap BioReagents cell lines for LRP6

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

    Gene Ontology (GO): 5/11 molecular function terms (GO ID links to tree view) (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 IPI17804805
    GO:0017147Wnt-protein binding IPI11029007


    LRP6 for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for LRP6: Lrp6tm1.2Vari Lrp6tm1.2Cjz
         15/21 MGI mutant phenotypes (inferred from 9 alleles) (MGI details for Lrp6) (see all 21):
     adipose tissue  behavior/neurological  cellular  craniofacial  digestive/alimentary 
     embryogenesis  growth/size  hearing/vestibular/ear  homeostasis/metabolism  integument 
     limbs/digits/tail  liver/biliary system  mortality/aging  nervous system  no phenotypic analysis 

    LRP6 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for LRP6 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/10 super-pathways (see all 10) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Wnt Signaling Pathway
    		Wnt Signaling Pathway and Pluripotency0.55
    		Wnt signaling pathway0.30
    		Wnt Signaling Pathway0.33
    		Wnt Signaling Pathway NetPath0.22
    2Wnt / Hedgehog / Notch
    		Wnt / Hedgehog / Notch1.00
    3WNT Signaling
    		WNT Signaling1.00
    4Reelin Pathway (Cajal-Retzius cells)
    		Reelin Pathway (Cajal-Retzius cells)1.00
    5MicroRNAs in cardiomyocyte hypertrophy
    		MicroRNAs in cardiomyocyte hypertrophy1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 R&D Systems Pathway for LRP6
        Wnt Signaling Pathway

    4 Downloadable PowerPoint Slides of QIAGEN 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

    5/6 BioSystems Pathways for LRP6 (see all 6) 
        Wnt Signaling Pathway and Pluripotency
    MicroRNAs in cardiomyocyte hypertrophy
    Wnt Signaling Pathway NetPath
    Canonical Wnt signaling pathway
    Wnt signaling network


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


    LRP6 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for LRP6

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

    5/56 Interacting proteins for LRP6 (O755811, 2, 3 ENSP000002613494) via UniProtKB, MINT, STRING, and/or I2D (see all 56)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DAB2P980822MINT-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
    ANTXR1Q9H6X21, 3, ENSP000003019454EBI-910915,EBI-905643 I2D: score=2 STRING: ENSP00000301945
    AMMECR1Q9Y4X02MINT-8183643 MINT-8183454 MINT-8183525 MINT-8183661 MINT-8183678 MINT-8183545
    WNT1P046283, ENSP000002935494I2D: score=3 STRING: ENSP00000293549
    DKK1O949073, ENSP000003630814I2D: score=2 STRING: ENSP00000363081
    About this table

    Gene Ontology (GO): 5/90 biological process terms (GO ID links to tree view) (see all 90):    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--


    LRP6 for ontologies           About GeneDecksing



    Drugs & Compounds
    for LRP6 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    LRP6 for compounds           About GeneDecksing

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

    Browse Tocris compounds for LRP6
    3 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about LRP6 

    Transcripts
    for LRP6 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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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    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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    Clone
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    Primer
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      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat LRP6

    Additional cDNA 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 

    24/161 AceView cDNA sequences (see all 161):

    CA413467 AI765587 AI144434 AA488423 AA838728 AA347309 BI492505 AA126365 
    AA025391 AV646154 AW376180 BM668604 AI768638 AI174424 BM671716 BG569152 
    Z42077 BM981464 AI796948 AK094666 AI688250 AW510975 CD678976 CA415080 

    GeneLoc Exon Structure


    Expression
    for LRP6 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    LRP6 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AAATTAAATA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    LRP6 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    3 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    EpiblastEpiblastIntraembryonic Epiblast CellsEarly Embryo
    Paraxial MesodermParaxial MesodermParaxial Mesoderm CellsMesoderm
    Primitive StreakPrimitive StreakPrimitive Streak CellsEarly Embryo
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See LRP6 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for LRP6

    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

        SABiosciences Expression via Pathway-Focused 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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    In Situ
    Assay Products:     
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    Orthologs
    for LRP6 gene

    (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
    This gene was present in the common ancestor of animals.

    Orthologs for LRP6 gene from 5/20 species (see all 20)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves LRP61 low density lipoprotein receptor-related protein 6 82.21(n)
    93.06(a)    		   419097  XM_417286.3  XP_417286.3 
    lizard
    (Anolis carolinensis)    		 Reptilia LRP66
    		 --
    		 90(a)
    		 1 ↔ 1
    		 5(83078166-83141666)
    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 arr3 Wnt receptor signaling pathway low-density
    lipoprotein more    		 42(a)     --


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

    Paralogs
    for LRP6 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for LRP6 gene
    LRP52  LRP22  SORL12  LRP1B2  EGF2  LDLR2  LRP5L2  LRP42  
    VLDLR2  NID22  NID12  LRP82  LRP12  
    10 SIMAP similar genes for LRP6 using alignment to 6 protein entries:     LRP6_HUMAN (see all proteins):
    LRP5    LRP5L    LRP4    LRP1    LDLR    LRP1B
    LRP8    LRP3    VLDLR    SPINT1

    LRP6 for paralogs           About GeneDecksing



    Genomic Variants
    for LRP6 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2644 NCBI SNPs in LRP6 are shown (see all 2644)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 12 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs562599281,2
    		C,F,--12033710(+) AGAATC/AATCAC 1 -- ds50011Minor allele frequency- A:0.07NA 120
    rs169077361,2
    		C,F,H,--12033753(+) TGCATT/CTTATA 1 -- ds500111Minor allele frequency- C:0.13NA NS EA WA 694
    rs752407411,2
    		--12034007(+) GTGGCG/ACAATC 1 -- ds50011Minor allele frequency- A:0.01NA 120
    rs107725311,2
    		C,F,A,H,--12034613(+) CCATAT/CANNNN 1 -- ut314Minor allele frequency- C:0.06NA WA EA 362
    rs1996795221,2
    		C--12034660(-) AAAGGA/GAAAAT 1 -- ut310--------
    rs110546951,2
    		C,F,--12034898(+) TCATTT/GAGTTT 1 -- ut313Minor allele frequency- G:0.07WA NA EA 358
    rs1156436841,2
    		C,F,--12035674(+) TTCCTA/GTGGCA 1 -- ut311Minor allele frequency- G:0.05WA 118
    rs714571291,2
    		C,--12035808(+) AACGCA/GTNNNN 1 -- ut313Minor allele frequency- G:0.05NA EA 242
    rs759373241,2
    		--12036231(+) TTGGTA/GATGTA 1 -- ut312Minor allele frequency- G:0.11CSA WA 120
    rs714571301,2
    		C,F,--12036822(+) ACTGTC/TCATGT 1 -- ut314Minor allele frequency- T:0.06NA EA 244

    HapMap Linkage Disequilibrium report for LRP6 (12268959 - 12419946 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for LRP6: --
    Human Gene Mutation Database (HGMD): LRP6

    SABiosciences Cancer Mutation PCR Assays
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    DNA2.0 Custom Variant and Variant Library Synthesis for LRP6

    Disorders / Diseases
    for LRP6 gene

    (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.)
    About This Section
    LRP6 for disorders           About GeneDecksing

    OMIM gene information: 603507   
    OMIM disorders: 610947  
    UniProtKB/Swiss-Prot: LRP6_HUMAN, O75581
  • Defects in LRP6 are a cause of coronary artery disease, autosomal dominant, type 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

    20/28 diseases for LRP6 (see all 28):    About MalaCards
    sost-related sclerosing bone dysplasia    coronary artery disease, autosomal dominant, 2    neural tube defect    age related macular degeneration
    testicular germ cell tumor    type 2 diabetes mellitus    germ cell tumor    macular degeneration
    diabetes mellitus    ulcerative colitis    coloboma    osteoporosis
    embryonal carcinoma    microphthalmia    colorectal cancer    breast cancer
    pulmonary disease    alzheimer's disease    colon cancer    osteoarthritis

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

    7 Novoseek 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

    Publications
    for LRP6 gene

    (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)
    About This Section

    PubMed articles for LRP6 gene, integrated from 9 sources (see all 178):
    (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. (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. (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. (2007)
    4. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. (PubMed id 17569865)1, 2, 9 Bilic J....Niehrs C. (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. (2007)
    6. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling co mplex reveals multiple Wnt and Dkk1 binding sites on LRP6. (PubMed id 20093360)1, 2, 9 Bourhis E....Hannoush R.N. (2010)
    7. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. (PubMed id 16513652)1, 2, 9 Swiatek W....Virshup D.M. (2006)
    8. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. (PubMed id 11448771)1, 2, 9 Semenov M.V....He X. (2001)
    9. 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. (2009)
    10. Palmitoylation and ubiquitination regulate exit of the Wnt signaling protein LRP6 from the endoplasmic reticulum. (PubMed id 18378904)1, 2, 9 Abrami L....van der Goot F.G. (2008)

    External Searches for LRP6 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing LRP6 gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 4040 HGNC: 6698 AceView: LRP6 Ensembl:ENSG00000070018 euGenes: HUgn4040
    ECgene: LRP6 Kegg: 4040 H-InvDB: LRP6

    Other Databases showing LRP6 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing LRP6 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for LRP6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for LRP6 Genetics and Cytogenetics in Oncology and Haematology

    Intellectual Property
    for LRP6 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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



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    About This Section

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