LRP6 LDL receptor related protein 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRP6provided by HGNC
Official Full Name: LDL receptor related protein 6provided by HGNC
Primary source: HGNC:HGNC:6698
See related: Ensembl:ENSG00000070018 MIM:603507
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: ADCAD2; STHAG7
Summary: 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]
Expression: Ubiquitous expression in placenta (RPKM 10.1), ovary (RPKM 7.4) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12p13.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (12116025..12267044, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (12268959..12419811, complement)

Chromosome 12 - NC_000012.12 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?

Low-density lipoprotein receptor-related protein 6-mediated signaling pathways and associated cardiovascular diseases: diagnostic and therapeutic opportunities.
Title: Low-density lipoprotein receptor-related protein 6-mediated signaling pathways and associated cardiovascular diseases: diagnostic and therapeutic opportunities.
Authors show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway.
Title: WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.
miR629 suppressed the development and progression of CRC by directly targeting LRP6 and inhibiting the Wnt/betacatenin pathway both in vitro and in vivo. Therefore, miR629 may be a novel prognostic biomarker and therapeutic target in CRC
Title: Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6.
MEG3 functions as a potential hepatocyte lipid degeneration suppressor. MEG3 helps to alleviate lipid over-deposition, probably by binding to miR-21 to regulate the expression of LRP6.
Title: LncRNA MEG3 functions as a ceRNA in regulating hepatic lipogenesis by competitively binding to miR-21 with LRP6.
High LRP6 expression is associated with hepatocarcinogenesis.
Title: C-terminal truncated HBx protein activates caveolin-1/LRP6/β-catenin/FRMD5 axis in promoting hepatocarcinogenesis.
LRP6 regulates alternative pre-mRNA splicing.
Title: Low-density lipoprotein receptor-related protein 6 regulates alternative pre-mRNA splicing.
We identified rare damaging variants in four genes known to be mutated in syndromic lip and/or cleft palate (syCL/P) : TP63 (one family), TBX1 (one family), LRP6 (one family) and GRHL3 (two families), and clinical reassessment confirmed the isolated nature of their lip and/or cleft palate (CL/P).
Title: Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes.
LRP6 rs2302685 (V1062I) variant carriers are associated with an increased risk of hyperlipidemia in Iranian children and adolescents.
Title: The association of LRP6 rs2302685 (V1062I) polymorphism with the risk of hyperlipidemia in Iranian children and adolescents.
Results indicate the key role in the interaction of LY6/PLAUR domain containing 6 (LYPD6) with LDL receptor related protein 6 (LRP6).
Title: Structure of the Wnt signaling enhancer LYPD6 and its interactions with the Wnt coreceptor LRP6.
low-expressed LRP6 may be responsible of lower migration and invasion of extravillous trophoblasts and subsequent preeclampsia.
Title: Downregulated low-density lipoprotein receptor-related protein 6 induces the maldevelopment of extravillous trophoblast via Wnt/β-catenin signaling pathway.

Submit: New GeneRIF Correction See all GeneRIFs (154)

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
Coronary artery disease, autosomal dominant 2 MedGen: C1970440 OMIM: 610947 GeneReviews: Not available	Compare labs
Tooth agenesis, selective, 7 MedGen: C4225231 OMIM: 616724 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genetics of coronary artery calcification among African Americans, a meta-analysis. NHGRI GWA Catalog NHGRI GWA 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

D12S1310 (e-PCR)
- UniSTS:73986

RH70320 (e-PCR)
- UniSTS:58218

RH80314 (e-PCR)
- UniSTS:89732

G41288 (e-PCR)
- UniSTS:20362

Lrp6 (e-PCR), detects polymorphism
- UniSTS:507036

BTA05_16075:706838514:1 (e-PCR)
- UniSTS:267949

MARC_16075-16076:1041970786:1 (e-PCR)
- UniSTS:267949

Lrp6 (e-PCR), detects polymorphism
- UniSTS:528050

G41286 (e-PCR)
- UniSTS:80060

RH104205 (e-PCR)
- UniSTS:98530

LRP6_4011 (e-PCR)
- UniSTS:462321

Homology

Homologs of the LRP6 gene: The LRP6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 294 organisms have orthologs with human gene LRP6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
Wnt-activated receptor activity	IEA Inferred from Electronic Annotation more info
Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
Wnt-protein binding	TAS Traceable Author Statement more info	PubMed
apolipoprotein binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
coreceptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
coreceptor activity involved in Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
coreceptor activity involved in canonical Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
frizzled binding	IPI Inferred from Physical Interaction more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
kinase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
low-density lipoprotein particle receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
low-density lipoprotein particle receptor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
toxin transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
NOT toxin transmembrane 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 involved in midbrain dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
Wnt signaling pathway involved in somitogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
anterior/posterior pattern specification	IBA Inferred from Biological aspect of Ancestor more info	PubMed
axis elongation involved in somitogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
beta-catenin destruction complex disassembly	TAS Traceable Author Statement more info
bone morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
bone remodeling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
branching involved in mammary gland duct morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
canonical Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
canonical Wnt signaling pathway involved in neural crest cell differentiation	IC Inferred by Curator more info	PubMed
canonical Wnt signaling pathway involved in regulation of cell proliferation	IC Inferred by Curator more info	PubMed
cell-cell adhesion	IEA Inferred from Electronic Annotation more info
cellular response to cholesterol	IMP Inferred from Mutant Phenotype more info	PubMed
cerebellum morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cerebral cortex development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info	PubMed
convergent extension	IBA Inferred from Biological aspect of Ancestor more info	PubMed
dopaminergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
embryonic camera-type eye morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
embryonic limb morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
embryonic pattern specification	IBA Inferred from Biological aspect of Ancestor more info	PubMed
embryonic retina morphogenesis in camera-type eye	IBA Inferred from Biological aspect of Ancestor more info	PubMed
external genitalia morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
face morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
gastrulation with mouth forming second	IBA Inferred from Biological aspect of Ancestor more info	PubMed
midbrain development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
midbrain dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
midbrain-hindbrain boundary development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of canonical Wnt signaling pathway	TAS Traceable Author Statement more info
negative regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of smooth muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
neural crest cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neural crest cell differentiation	IDA Inferred from Direct Assay more info	PubMed
neural crest formation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neural crest formation	IDA Inferred from Direct Assay more info	PubMed
neural tube closure	IBA Inferred from Biological aspect of Ancestor more info	PubMed
odontogenesis of dentin-containing tooth	IBA Inferred from Biological aspect of Ancestor more info	PubMed
pericardium morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
primitive streak formation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein localization to plasma membrane	IPI Inferred from Physical Interaction more info	PubMed
receptor-mediated endocytosis involved in cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of ossification	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to peptide hormone	IEA Inferred from Electronic Annotation more info
roof of mouth development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
thalamus development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
toxin transport	IEA Inferred from Electronic Annotation more info
trachea cartilage morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
Wnt signalosome	IDA Inferred from Direct Assay more info	PubMed
Wnt signalosome	NAS Non-traceable Author Statement more info	PubMed
Wnt-Frizzled-LRP5/6 complex	IDA Inferred from Direct Assay more info	PubMed
Wnt-Frizzled-LRP5/6 complex	IPI Inferred from Physical Interaction more info	PubMed
Wnt-Frizzled-LRP5/6 complex	TAS Traceable Author Statement more info	PubMed
colocalizes_with caveola	IDA Inferred from Direct Assay more info	PubMed
cell	IEA Inferred from Electronic Annotation more info
cell surface	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with early endosome	IDA Inferred from Direct Assay more info	PubMed
early endosome membrane	TAS Traceable Author Statement more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
extracellular region	TAS Traceable Author Statement more info
integral component of membrane	IEA Inferred from Electronic Annotation more info
neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
synapse	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: low-density lipoprotein receptor-related protein 6

Names: LRP-6

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_016168.2 RefSeqGene

Range

4834..155853

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002336.3 → NP_002327.2 low-density lipoprotein receptor-related protein 6 precursor

See identical proteins and their annotated locations for NP_002327.2

Status: REVIEWED

Source sequence(s)

AA126261, AC007537, AC007621, AF074264, BC126405, BP229563

Consensus CDS

CCDS8647.1

UniProtKB/Swiss-Prot

O75581

Related

ENSP00000261349.4, ENST00000261349.9

Conserved Domains (6) summary

smart00135
Location:483 → 524

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1326 → 1360

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:55 → 93

NHL; NHL repeat [structural motif]

pfam00058
Location:150 → 190

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:592 → 627

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:55 → 272

NHL; NHL repeat unit of beta-propeller proteins

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

12116025..12267044 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011520671.3 → XP_011518973.1 low-density lipoprotein receptor-related protein 6 isoform X2

See identical proteins and their annotated locations for XP_011518973.1

Conserved Domains (4) summary

smart00135
Location:332 → 373

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1175 → 1209

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:1 → 39

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:441 → 476

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_006719078.4 → XP_006719141.1 low-density lipoprotein receptor-related protein 6 isoform X1

See identical proteins and their annotated locations for XP_006719141.1

UniProtKB/Swiss-Prot

O75581

Related

ENSP00000445083.1, ENST00000538239.5

Conserved Domains (6) summary

smart00135
Location:483 → 524

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1326 → 1360

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:55 → 93

NHL; NHL repeat [structural motif]

pfam00058
Location:150 → 190

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:592 → 627

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:55 → 272

NHL; NHL repeat unit of beta-propeller proteins