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    LRP5 LDL receptor related protein 5 [ Homo sapiens (human) ]

    Gene ID: 4041, updated on 23-Aug-2016
    Official Symbol
    LRP5provided by HGNC
    Official Full Name
    LDL receptor related protein 5provided by HGNC
    Primary source
    HGNC:HGNC:6697
    See related
    Ensembl:ENSG00000162337 HPRD:04616; MIM:603506; Vega:OTTHUMG00000167570
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HBM; LR3; OPS; EVR1; EVR4; LRP7; OPPG; BMND1; LRP-5; OPTA1; VBCH2
    Summary
    This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
    Orthologs
    Location:
    11q13.4
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 11 NC_000011.10 (68298866..68449275)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (68080077..68216743)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369363 Neighboring gene chromosome 11 open reading frame 24 Neighboring gene protein phosphatase 6 regulatory subunit 3 Neighboring gene NADH:ubiquinone oxidoreductase subunit A3 pseudogene 2 Neighboring gene uncharacterized LOC107984343 Neighboring gene galanin and GMAP prepropeptide

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Bone mineral density quantitative trait locus 1
    MedGen: C1866079 OMIM: 601884 GeneReviews: Not available
    Compare labs
    Exudative vitreoretinopathy 1 Compare labs
    Exudative vitreoretinopathy 4 Compare labs
    Osteopetrosis autosomal dominant type 1
    MedGen: C1843330 OMIM: 607634 GeneReviews: Not available
    Compare labs
    Osteoporosis
    MedGen: C0029458 OMIM: 166710 GeneReviews: Not available
    Compare labs
    Osteoporosis with pseudoglioma
    MedGen: C0432252 OMIM: 259770 GeneReviews: Not available
    Compare labs
    Van Buchem disease type 2
    MedGen: C1843323 OMIM: 607636 GeneReviews: Not available
    Compare labs
    Worth disease
    MedGen: C0432273 OMIM: 144750 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2015-04-02)

    ClinGen Genome Curation Page
    Haploinsufficency

    Some evidence for dosage pathogenicity (Last evaluated (2015-04-02)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

    Description
    Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.
    NHGRI GWA Catalog
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
    NHGRI GWA Catalog
    Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.
    NHGRI GWA Catalog
    Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
    NHGRI GWA Catalog
    Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
    NHGRI GWA Catalog
    • Disassembly of the destruction complex and recruitment of AXIN to the membrane, organism-specific biosystem (from REACTOME)
      Disassembly of the destruction complex and recruitment of AXIN to the membrane, organism-specific biosystemUpon stimulation with WNT ligand, AXIN and GSK3beta are recruited to the plasma membrane through interaction with DVL (Tamai et al, 2004; Mao et al, 2001; reviewed in He et al, 2004). Polymerization...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
      MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
    • Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling, organism-specific biosystem (from REACTOME)
      Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling, organism-specific biosystemLRP5 is subject to an in-frame missplicing event in breast and parathyroid cancers that renders the protein insensitive to inhibition by the WNT antagonist DKK1. Expression of the mutant protein res...
    • N-cadherin signaling events, organism-specific biosystem (from Pathway Interaction Database)
      N-cadherin signaling events, organism-specific biosystem
      N-cadherin signaling events
    • Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystem (from REACTOME)
      Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystemSeveral unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, wh...
    • RNF mutants show enhanced WNT signaling and proliferation, organism-specific biosystem (from REACTOME)
      RNF mutants show enhanced WNT signaling and proliferation, organism-specific biosystemRNF43 and related protein ZNRF3 are E3 ubiquitin ligases that negatively regulate WNT signaling by downregulating FZD receptors at the cell surface (Mukai et al, 2010; Hao et al, 2012). Frameshift l...
    • Regulation of FZD by ubiquitination, organism-specific biosystem (from REACTOME)
      Regulation of FZD by ubiquitination, organism-specific biosystemWNT responsiveness is influenced by expression levels of FZD and LRP proteins. Levels of these receptors at the cell surface are regulated in part by endocytosis, but the mechanisms are not fully el...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by WNT in cancer, organism-specific biosystem (from REACTOME)
      Signaling by WNT in cancer, organism-specific biosystemThe WNT signaling pathway has been linked with cancer ever since the identification of the first WNT as a gene activated by integration of mouse mammary tumor virus proviral DNA in virally-induced br...
    • Signaling by Wnt, organism-specific biosystem (from REACTOME)
      Signaling by Wnt, organism-specific biosystemWNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Sai...
    • TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
      TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
    • Wnt Signaling Pathway NetPath, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway NetPath, organism-specific biosystemWnt family of proteins are a large family of cysteine-rich secreted glycoproteins that regulate cell-cell interactions. They bind to members of the Frizzled family of 7 transmembrane receptors. Bindi...
    • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell plurip...
    • Wnt signaling network, organism-specific biosystem (from Pathway Interaction Database)
      Wnt signaling network, organism-specific biosystem
      Wnt signaling network
    • Wnt signaling pathway, organism-specific biosystem (from KEGG)
      Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt signaling pathway, conserved biosystem (from KEGG)
      Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    Wnt-activated receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Wnt-activated receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Wnt-protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Wnt-protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Wnt-protein binding TAS
    Traceable Author Statement
    more info
    PubMed 
    coreceptor activity involved in Wnt signaling pathway IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    coreceptor activity involved in canonical Wnt signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    NOT toxin transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Wnt signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    Wnt signaling pathway involved in dorsal/ventral axis specification IDA
    Inferred from Direct Assay
    more info
    PubMed 
    adipose tissue development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    anatomical structure regression IEA
    Inferred from Electronic Annotation
    more info
     
    anterior/posterior pattern specification IEA
    Inferred from Electronic Annotation
    more info
     
    apoptotic process involved in patterning of blood vessels IEA
    Inferred from Electronic Annotation
    more info
     
    beta-catenin destruction complex disassembly TAS
    Traceable Author Statement
    more info
     
    bone marrow development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    bone morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    bone remodeling IEA
    Inferred from Electronic Annotation
    more info
     
    branching involved in mammary gland duct morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    canonical Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cell migration involved in gastrulation IEA
    Inferred from Electronic Annotation
    more info
     
    cell-cell signaling involved in mammary gland development IEA
    Inferred from Electronic Annotation
    more info
     
    cholesterol homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cholesterol metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    embryonic digit morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    endocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular matrix-cell signaling IEA
    Inferred from Electronic Annotation
    more info
     
    gastrulation with mouth forming second IEA
    Inferred from Electronic Annotation
    more info
     
    glucose catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of osteoblast differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of protein serine/threonine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    osteoblast development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of fat cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of mesenchymal cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of mitotic nuclear division IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of osteoblast proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of sequence-specific DNA binding transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of blood pressure IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of bone remodeling IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of insulin secretion involved in cellular response to glucose stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    retina morphogenesis in camera-type eye IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    retinal blood vessel morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    somatic stem cell population maintenance IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    Wnt signalosome NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Wnt-Frizzled-LRP5/6 complex TAS
    Traceable Author Statement
    more info
    PubMed 
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
     
    integral component of membrane IEA
    Inferred from Electronic Annotation
    more info
     
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    low-density lipoprotein receptor-related protein 5
    Names
    low density lipoprotein receptor-related protein 5
    low density lipoprotein receptor-related protein 7

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_015835.1 RefSeqGene

      Range
      4970..141636
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001291902.1NP_001278831.1  low-density lipoprotein receptor-related protein 5 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR and uses and alternate start codon, compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AB017498, AI583742, AP000807, BC098397, BC150595, DN999254
      UniProtKB/Swiss-Prot
      O75197
      Conserved Domains (5) summary
      smart00135
      Location:129171
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:755789
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      pfam14670
      Location:325360
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cd05819
      Location:105131
      NHL; NHL repeat [structural motif]
      cl18310
      Location:104297
      NHL; NHL repeat unit of beta-propeller proteins
    2. NM_002335.3NP_002326.2  low-density lipoprotein receptor-related protein 5 isoform 1 precursor

      See identical proteins and their annotated locations for NP_002326.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AB017498, AI583742, AP000807, BC150595, DN999254
      Consensus CDS
      CCDS8181.1
      UniProtKB/Swiss-Prot
      O75197
      Related
      ENSP00000294304, OTTHUMP00000236183, ENST00000294304, OTTHUMT00000395088
      Conserved Domains (7) summary
      smart00135
      Location:408450
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:13361370
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      cd05819
      Location:720756
      NHL; NHL repeat [structural motif]
      pfam00057
      Location:12581295
      Ldl_recept_a; Low-density lipoprotein receptor domain class A
      pfam00058
      Location:163203
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:299336
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cl18310
      Location:685878
      NHL; NHL repeat unit of beta-propeller proteins

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p7 Primary Assembly

      Range
      68298866..68449275
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011545029.1XP_011543331.1  

      Conserved Domains (6) summary
      smart00135
      Location:417459
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:13451379
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      pfam00058
      Location:172212
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:308345
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cd05819
      Location:695721
      NHL; NHL repeat [structural motif]
      cl18310
      Location:694887
      NHL; NHL repeat unit of beta-propeller proteins
    2. XM_011545030.1XP_011543332.1  

      Conserved Domains (6) summary
      smart00135
      Location:417459
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:13451379
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      pfam00058
      Location:172212
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:308345
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cd05819
      Location:695721
      NHL; NHL repeat [structural motif]
      cl18310
      Location:694887
      NHL; NHL repeat unit of beta-propeller proteins
    3. XM_011545031.1XP_011543333.1  

      Conserved Domains (6) summary
      smart00135
      Location:417459
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:13451379
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      pfam00058
      Location:172212
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:308345
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cd05819
      Location:695721
      NHL; NHL repeat [structural motif]
      cl18310
      Location:694887
      NHL; NHL repeat unit of beta-propeller proteins
    4. XM_005273994.2XP_005274051.1  

      Conserved Domains (6) summary
      smart00135
      Location:408450
      LY; Low-density lipoprotein-receptor YWTD domain
      cd00112
      Location:13361370
      LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
      pfam00058
      Location:163203
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:299336
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cd05819
      Location:686712
      NHL; NHL repeat [structural motif]
      cl18310
      Location:685878
      NHL; NHL repeat unit of beta-propeller proteins
    5. XM_017017735.1XP_016873224.1  

    6. XM_017017736.1XP_016873225.1  

    RNA

    1. XR_949926.2 RNA Sequence

    2. XR_949925.2 RNA Sequence

      Related
      ENST00000529993, OTTHUMT00000395089
    3. XR_001747874.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018922.2 Alternate CHM1_1.1

      Range
      67964539..68100925
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)