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

Summary

Official Symbol: LRP5provided by HGNC
Official Full Name: LDL receptor related protein 5provided by HGNC
Primary source: HGNC:HGNC:6697
See related: Ensembl:ENSG00000162337 MIM:603506; AllianceGenome:HGNC:6697
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; LRP-7; OPTA1; PCLD4; 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]
Expression: Ubiquitous expression in fat (RPKM 20.9), small intestine (RPKM 15.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (68298412..68449275)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (68302748..68454184)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (68080059..68216743)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Unveiling novel LRP5 pathogenic variant in familial exudative vitreoretinopathy: Diverse phenotypic expressions in a mother-daughter duo.
Title: Unveiling novel LRP5 pathogenic variant in familial exudative vitreoretinopathy: Diverse phenotypic expressions in a mother-daughter duo.
Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.
Title: Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.
Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.
Title: Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.
LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.
Title: LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.
Relationship between polymorphisms and mutations at rs7125942 and rs3736228 of LRP5 gene and bone metabolism in postmenopausal women.
Title: Relationship between polymorphisms and mutations at rs7125942 and rs3736228 of LRP5 gene and bone metabolism in postmenopausal women.
Genetic detection of two novel LRP5 pathogenic variants in patients with familial exudative vitreoretinopathy.
Title: Genetic detection of two novel LRP5 pathogenic variants in patients with familial exudative vitreoretinopathy.
LRP5, Bone Mass Polymorphisms and Skeletal Disorders.
Title: LRP5, Bone Mass Polymorphisms and Skeletal Disorders.
Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies.
Title: Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies.
LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma.
Title: LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma.
Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori.
Title: Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori.

Submit: New GeneRIF Correction See all GeneRIFs (235)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant osteopetrosis 1 MedGen: C1843330 OMIM: 607634 GeneReviews: Not available	Compare labs
Bone mineral density quantitative trait locus 1 MedGen: C1866079 OMIM: 601884 GeneReviews: Not available	Compare labs
Exudative vitreoretinopathy 1 MedGen: C1851402 OMIM: 133780 GeneReviews: Not available	Compare labs
Exudative vitreoretinopathy 4 MedGen: C1866176 OMIM: 601813 GeneReviews: Not available	Compare labs
Osteoporosis with pseudoglioma MedGen: C0432252 OMIM: 259770 GeneReviews: Not available	Compare labs
Polycystic liver disease 4 with or without kidney cysts MedGen: C4693479 OMIM: 617875 GeneReviews: Not available	Compare labs
Worth disease MedGen: C0432273 OMIM: 144750 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2024-04-09) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2024-04-09) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. EBI GWAS Catalog EBI GWAS CatalogPubMed
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. EBI GWAS Catalog EBI GWAS CatalogPubMed
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-144578 (e-PCR)
- UniSTS:172290

D11S1337 (e-PCR), detects polymorphism
- UniSTS:4872

AFM289ya9 (e-PCR), detects polymorphism
- UniSTS:90934

D11S3666 (e-PCR)
- UniSTS:152900

RH12415 (e-PCR)
- UniSTS:76167

G60523 (e-PCR)
- UniSTS:137629

D11S4087 (e-PCR), detects polymorphism
- UniSTS:49857

D11S4178 (e-PCR), detects polymorphism
- UniSTS:26567

RH11806 (e-PCR)
- UniSTS:46047

D11S970 (e-PCR)
- UniSTS:84458

G40260 (e-PCR)
- UniSTS:61688

D11S987 (e-PCR), detects polymorphism
- UniSTS:61688

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Wnt receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables Wnt receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables Wnt-protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables Wnt-protein binding	TAS Traceable Author Statement more info	PubMed
enables coreceptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables coreceptor activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables toxin transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Norrin signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adipose tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amino acid transport	IEA Inferred from Electronic Annotation more info
involved_in anatomical structure regression	IEA Inferred from Electronic Annotation more info
involved_in anterior/posterior pattern specification	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in bone marrow development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bone morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bone remodeling	IEA Inferred from Electronic Annotation more info
involved_in branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell migration involved in gastrulation	IEA Inferred from Electronic Annotation more info
involved_in cell-cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cell-cell signaling involved in mammary gland development	IEA Inferred from Electronic Annotation more info
involved_in cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in establishment of blood-brain barrier	IEA Inferred from Electronic Annotation more info
involved_in establishment of blood-retinal barrier	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in gastrulation with mouth forming second	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in glucose catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesodermal cell migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in osteoblast development	IEA Inferred from Electronic Annotation more info
involved_in osteoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of fat cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mesenchymal cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mitotic nuclear division	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of osteoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of insulin secretion involved in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to peptide hormone	IEA Inferred from Electronic Annotation more info
involved_in retina morphogenesis in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retinal blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of Wnt signalosome	NAS Non-traceable Author Statement more info	PubMed
part_of Wnt-Frizzled-LRP5/6 complex	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: low-density lipoprotein receptor-related protein 5

Names: low density lipoprotein receptor-related protein 5; low density lipoprotein receptor-related protein 7

NCBI Reference Sequences (RefSeq)

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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

NG_015835.3 RefSeqGene

Range

19181..155865

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001291902.2 → NP_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, AP002813, BC098397, BC150595, DN999254

UniProtKB/Swiss-Prot

O75197

Conserved Domains (6) summary

smart00135
Location:129 → 171

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:755 → 789

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:139 → 175

NHL; NHL repeat [structural motif]

pfam00057
Location:677 → 714

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam14670
Location:24 → 59

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:104 → 297

NHL; NHL repeat unit of beta-propeller proteins
NM_002335.4 → NP_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, AP002813, BC150595, DN999254

Consensus CDS

CCDS8181.1

UniProtKB/Swiss-Prot

O75197, Q96TD6, Q9UES7, Q9UP66

Related

ENSP00000294304.6, ENST00000294304.12

Conserved Domains (7) summary

smart00135
Location:408 → 450

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1336 → 1370

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:720 → 756

NHL; NHL repeat [structural motif]

pfam00057
Location:1258 → 1295

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:163 → 203

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:299 → 336

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:685 → 878

NHL; NHL repeat unit of beta-propeller proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

68298412..68449275

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011545031.2 → XP_011543333.1 low-density lipoprotein receptor-related protein 5 isoform X4

Conserved Domains (7) summary

smart00135
Location:417 → 459

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1345 → 1379

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:729 → 765

NHL; NHL repeat [structural motif]

pfam00057
Location:1267 → 1304

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:172 → 212

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:308 → 345

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:694 → 887

NHL; NHL repeat unit of beta-propeller proteins
XM_011545029.2 → XP_011543331.1 low-density lipoprotein receptor-related protein 5 isoform X1

Conserved Domains (7) summary

smart00135
Location:417 → 459

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1345 → 1379

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:729 → 765

NHL; NHL repeat [structural motif]

pfam00057
Location:1267 → 1304

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:172 → 212

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:308 → 345

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:694 → 887

NHL; NHL repeat unit of beta-propeller proteins
XM_011545030.2 → XP_011543332.1 low-density lipoprotein receptor-related protein 5 isoform X3

Conserved Domains (7) summary

smart00135
Location:417 → 459

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1345 → 1379

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:729 → 765

NHL; NHL repeat [structural motif]

pfam00057
Location:1267 → 1304

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:172 → 212

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:308 → 345

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:694 → 887

NHL; NHL repeat unit of beta-propeller proteins
XM_047426949.1 → XP_047282905.1 low-density lipoprotein receptor-related protein 5 isoform X6
XM_047426948.1 → XP_047282904.1 low-density lipoprotein receptor-related protein 5 isoform X5
XM_047426950.1 → XP_047282906.1 low-density lipoprotein receptor-related protein 5 isoform X7
XM_005273994.3 → XP_005274051.1 low-density lipoprotein receptor-related protein 5 isoform X2

Conserved Domains (7) summary

smart00135
Location:408 → 450

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1336 → 1370

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:720 → 756

NHL; NHL repeat [structural motif]

pfam00057
Location:1258 → 1295

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:163 → 203

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:299 → 336

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:685 → 878

NHL; NHL repeat unit of beta-propeller proteins
XM_017017735.2 → XP_016873224.1 low-density lipoprotein receptor-related protein 5 isoform X8
XM_017017736.2 → XP_016873225.1 low-density lipoprotein receptor-related protein 5 isoform X9

RNA

XR_001747874.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

68302748..68454184

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368788.1 → XP_054224763.1 low-density lipoprotein receptor-related protein 5 isoform X4
XM_054368785.1 → XP_054224760.1 low-density lipoprotein receptor-related protein 5 isoform X1
XM_054368787.1 → XP_054224762.1 low-density lipoprotein receptor-related protein 5 isoform X3
XM_054368790.1 → XP_054224765.1 low-density lipoprotein receptor-related protein 5 isoform X6
XM_054368789.1 → XP_054224764.1 low-density lipoprotein receptor-related protein 5 isoform X5
XM_054368791.1 → XP_054224766.1 low-density lipoprotein receptor-related protein 5 isoform X7
XM_054368793.1 → XP_054224768.1 low-density lipoprotein receptor-related protein 5 isoform X10
XM_054368786.1 → XP_054224761.1 low-density lipoprotein receptor-related protein 5 isoform X2
XM_054368792.1 → XP_054224767.1 low-density lipoprotein receptor-related protein 5 isoform X8