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
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Genomic context

Location:: 12p13.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (12116025..12267044, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (12268959..12419978, 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?

TRAP1 Regulates Wnt/beta-Catenin Pathway through LRP5/6 Receptors Expression Modulation.
Title: TRAP1 Regulates Wnt/β-Catenin Pathway through LRP5/6 Receptors Expression Modulation.
Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains.
Title: Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains.
Cardiac-specific LRP6 knockout induces lipid accumulation through Drp1/CPT1b pathway in adult mice.
Title: Cardiac-specific LRP6 knockout induces lipid accumulation through Drp1/CPT1b pathway in adult mice.
VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6.
Title: VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6.
New explanation for autosomal dominant high bone mass: Mutation of low-density lipoprotein receptor-related protein 6.
Title: New explanation for autosomal dominant high bone mass: Mutation of low-density lipoprotein receptor-related protein 6.
Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6.
Title: Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6.
We found that the rs2302685 mutation, which impaired the function of LRP6, was present in higher frequency among alcoholics with alcoholic liver disease than those without alcoholic liver disease
Title: The LRP6 functional mutation rs2302685 contributes to individual susceptibility to alcoholic liver injury related to the Wnt/β-catenin-TCF1-CYP2E1 signaling pathway.
association of LRP5 intronic rs4988319 and rs3736228 (Ala1330Val) with attention deficit and hyperactivity disorder (cADHD) was observed among girls, whereas in boys association between LRP6 rs2302685 (Val1062Ile) and cADHD was present (OR = 1.66, CI = 1.20-2.31, p = .0024). In the PGC-ADHD dataset tendency of associations were observed only among females for LRP5 rs3736228 and for LRP6 rs2302685.
Title: The involvement of the canonical Wnt-signaling receptor LRP5 and LRP6 gene variants with ADHD and sexual dimorphism: Association study and meta-analysis.
the results together with previous data such as the development of Split-hand/foot malformation (SHFM) in Lrp6 knockout mice, the presence of SHFM in two subjects with 19q13 deletions involving UBA2, and strong mouse Uba2 expression in the developing limb buds, imply that LRP6 and UBA2 represent plausible candidate genes for SHFM.
Title: Comprehensive clinical and molecular studies in split-hand/foot malformation: identification of two plausible candidate genes (LRP6 and UBA2).
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.

Submit: New GeneRIF Correction See all GeneRIFs (163)

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
Genetics of coronary artery calcification among African Americans, a meta-analysis. GeneReviews: Not available
Tooth agenesis, selective, 7 MedGen: C4225231 OMIM: 616724 GeneReviews: Not available	Compare labs

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: 322 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
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
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 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 109.20210226

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

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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