Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol LRP5 contributors: shn/npt - updated : 17-05-2010
HGNC name low density lipoprotein receptor-related protein 5
HGNC id 6697
Corresponding disease
EVR4 familial, exudative vitreoretinopathy 4
HBMCS high bone mass phenotype in association with craniosynostosis
HVB2 van Buchem disease, type 2
OPPG osteoporosis-pseudoglioma syndrome
OPTA1 osteopetrosis type I
Location 11q13.2      Physical location : 68.080.107 - 68.216.739
Synonym name low density lipoprotein receptor-related protein 7
Synonym symbol(s) LRP7, LR3, BMND1, HBM, OPS, VBCH2,EVR4, OPPG, VBCH2
DNA
TYPE functioning gene
STRUCTURE 136.64 kb     23 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D11S987 - D11S4155 - LRP5 - D11S4113 - D11S4095 - qter
Physical map
ALDH3B2 11q13 aldehyde dehydrogenase 3 family, member B2 RPL37P2 11q13 ribosomal protein L37 pseudogene 2 LOC132740 11q13.1 similar to unc-93 homolog B1; unc93 (C.elegans) homolog B; unc-93 related protein LOC390215 11 similar to seven transmembrane helix receptor OR7E11P 11q11 olfactory receptor, family 7, subfamily E, member 11 pseudogene LOC390216 11 similar to mannosyltransferase LOC158490 11q13.1 similar to hypothetical protein FLJ10661 LOC387785 11 LOC387785 LOC390217 11 similar to chromosome 11 open reading frame2; chromosome  11 open reading frame2 LOC341128 11q13.1 similar to seven transmembrane helix receptor UNC93B1 11q13 unc-93 homolog B1 (C. elegans) ALDH3B1 11q13 aldehyde dehydrogenase 3 family, member B1 NDUFS8 11q13 NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) TCIRG1 11q13.4-q13.5 T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein a isoform 3 CHK 11q13.1 choline kinase CGI-85 11q13 choline kinase C11orf24 11q13 chromosome 11 open reading frame 24 LRP5 11q13 low density lipoprotein receptor-related protein 5 C11orf23 11q13 chromosome 11 open reading frame 23 GAL 11q13.3-q13.5 galanin MTL5 11q13.2-q13.3 metallothionein-like 5, testis-specific (tesmin) CPT1A 11q13.1-q13.2 carnitine palmitoyltransferase 1A (liver)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
23 - 5161 179 1615 - Dong (1998)
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvesselsaorta   
Digestiveliver   predominantly
Endocrinepancreas   highly
Nervousbrain   moderately
Reproductivemale systemprostate  moderately
Respiratorylung   highly
Urinarykidney   highly
Visualeyeretina   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Epithelialsecretoryglandularendocrine 
Epithelialsecretoryglandularexocrine 
cells
SystemCellPubmedSpeciesStageRna symbol
Skeletonosteoblast
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text primary vasculature vitreal
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal extracellular domain binds to Wnt ligands
  • putative signal peptide for protein export
  • four domains consisiting of six YWTD spacer repeats (LY domain)
  • four epidermal growth factor (EGF) repeats with associated spacer domains
  • three LDL-receptor (LDLR)ligand binding domains
  • a single transmembrane spanning domain
  • a proline rich cytoplasmic domain, containing motifs involved in the endocytosis of receptors
  • C-terminal intracellular domain is important for signaling events
  • HOMOLOGY
    interspecies ortholog to Lrp5, Mus musculus
    ortholog to Lrp5, Rattus norvegicus
    ortholog to lrp5, Danio rerio
    intraspecies homolog to low density lipoprotein receptor 1 (LDLR)
    Homologene
    FAMILY
  • LDLR family
  • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • playing a role in the WNT signaling pathway probably by acting as a coreceptor together with frizzled for WNT and in lipid metabolism
  • involved in the regulation of bone mass
  • LRP5 signaling is essential for normal morphology, developmental processes and bone health
  • being essential for the development of retinal vasculature, and playing a role in capillary maturation
  • essential for normal cholesterol metabolism and glucose-induced insulin secretion (Fujino et al, 2003)
  • Fz4/Lrp5 signaling could play a role in vascular growth, remodeling, and maintenance in a variety of normal and pathologic contexts beyond the retina (Ye et al, 2009)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cell to cell transport
    text intercellular transport
    PATHWAY
    metabolism lipid/lipoprotein
    signaling sensory transduction/vision
    WNT signaling pathway
    a component FZD4, LRP5, and TSPAN12 are component of the Norrin-FZD4 complex
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • axin and regulates the canonical Wnt signaling pathway (Mao et a, 2001)
  • WNT/frizzled complexes
  • SOST a ligand for LRP5/LRP6 (Semënov et al, 2005)
  • CDH2-axin1-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass (HAY 2009)
  • CAPRIN2-binding protein
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OPPG , HVB2 , OPTA1 , HBMCS , EVR4
    Susceptibility
  • to osteoporosis, idiopathic osteoporosis in males
  • to obesity
  • Variant & Polymorphism SNP , other
  • variant contributing to spinal bone mass, to osteoporosis and size determination
  • SNPs in intron 1 associated with an increased risk of obesity
  • mutation R1036Q associated to osteoporosis in both children and adults
  • polymorphisms associated to idiopathic osteoporosis in men
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis
    osteoarticularboneostéoporosis
    SOST-LRP5 antagonistic interaction plays a central role in bone mass regulation and may represent a nodal point for therapeutic intervention for osteoporosis and other bone diseases
    ANIMAL & CELL MODELS
  • mice with Lrp5 disruption develop a low bone mass phenotype and display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis (Kato et al, 2002)
  • mice lacking LRP5 have increased plasma cholesterol levels and a markedly impaired glucose tolerance (Fujino et al, 2003)
  • lithium restored bone metabolism and bone mass near to wild-type levels in Lrp5 deficient mice (Clément-Lacroix et al, 2005)
  • mice lacking LRP5 and apolipoprotein E display severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis (Magoori et al, 2003)
  • Lrp5-/- mice have a leaky and aberrant retinal vasculature (Junge et al, 2009)
  • mice with a loss of LRP5 display underdeveloped intraretinal vasculature associated with endothelial cell (EC) clustering and failed EC migration into deep retinal layers