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 : 17-05-2018

HGNC name	low density lipoprotein receptor-related protein 5
HGNC id	6697

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002335 23 - 5161 NP_002326 179 1615 - Dong (1998)

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessels aorta       Digestive liver       predominantly Endocrine pancreas       highly Nervous brain       moderately Reproductive male system prostate     moderately Respiratory lung       highly Urinary kidney       highly Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine

cells

System Cell Pubmed Species Stage Rna symbol Skeleton osteoblast

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
	instead of inducing FZD4 dimerization, NDP induces the formation of a ternary complex with FZD4 and LRP5/6 by binding to their respective extracellular domains

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
	MESD is a specialized chaperone for low-density lipoprotein receptor-related protein 5 (LRP5) and LRP6
	LRP5 physically interacted with GCGR
	NFIC directly binds to the promoter of low-density lipoprotein receptor-related protein 5 (LRP5) and thereafter transactivates the promoter
	when RGMB is phosphorylated by the extracellular tyrosine kinase PKDCC, phosphorylated RGMB (p-RGMb) is internalized and carries LRP5 towards intracellular compartments

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
	System Type Disorder Pubmed osteoarticular bone ostéoporosis increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis osteoarticular bone ostéoporosis 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