LRP6 Gene

HGNC Family	Low density lipoprotein receptors
Name	low density lipoprotein receptor-related protein 6
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRP6 is an essential cell‐surface co‐receptor that, together with Frizzled proteins, mediates canonical Wnt signaling by binding Wnt ligands and transmitting signals that stabilize β–catenin and activate downstream target gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Upon Wnt stimulation, LRP6 undergoes rapid phosphorylation and clusters at the plasma membrane in signalosomes; this event requires recruitment of Dishevelled and an Axin–GSK3 complex that ultimately facilitates β–catenin accumulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, extracellular modulators such as Dickkopf1 and Kremen negatively regulate Wnt signaling by binding to LRP6 and inducing its internalization and turnover, whereas R-spondin proteins act to enhance signaling by stabilizing LRP6 surface levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In developmental and tissue-specific contexts, LRP6 functions to regulate cell fate decisions, pattern posterior mesoderm formation during gastrulation, and modulate skeletal formation through interactions with factors such as Sclerostin and Wise."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, mutations in LRP6 that impair its co-receptor activity have been linked to human diseases including cardiovascular disorders and altered bone density, highlighting its role in tissue homeostasis and as a potential therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " In the central nervous system, for example, LRP6 participates in a receptor complex with Frizzled and accessory factors such as Gpr124 to regulate brain angiogenesis and barrier formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, LRP6 integrates extracellular cues to determine the balance between β–catenin stabilization and the modulation of noncanonical pathways, thereby influencing diverse processes including embryonic patterning, tissue regeneration, and stem cell maintenance.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bingyu Mao, Wei Wu, Gary Davidson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature756"}], "href": "https://doi.org/10.1038/nature756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12050670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12050670"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Josipa Bilic, Ya-Lin Huang, Gary Davidson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1137065"}], "href": "https://doi.org/10.1126/science.1137065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17569865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17569865"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xin Zeng, He Huang, Keiko Tamai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.013540"}], "href": "https://doi.org/10.1242/dev.013540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077588"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ju-Suk Nam, Taryn J Turcotte, Peter F Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M508324200"}], "href": "https://doi.org/10.1074/jbc.M508324200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16543246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16543246"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Minke E Binnerts, Kyung-Ah Kim, Jessica M Bright, et al. "}, {"type": "b", "children": [{"type": "t", "text": "R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0702305104"}], "href": "https://doi.org/10.1073/pnas.0702305104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17804805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17804805"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sheri L Holmen, Troy A Giambernardi, Cassandra R Zylstra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1359/JBMR.040907"}], "href": "https://doi.org/10.1359/JBMR.040907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15537447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15537447"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Debra L Ellies, Beth Viviano, John McCarthy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1359/jbmr.060810"}], "href": "https://doi.org/10.1359/jbmr.060810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17002572"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17002572"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Atsuhiko T Naito, Tomokazu Sumida, Seitaro Nomura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.03.047"}], "href": "https://doi.org/10.1016/j.cell.2012.03.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22682250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22682250"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Olivia G Kelly, Kathy I Pinson, William C Skarnes "}, {"type": "b", "children": [{"type": "t", "text": "The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01137"}], "href": "https://doi.org/10.1242/dev.01137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15142971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15142971"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Giancarlo V De Ferrari, Andreas Papassotiropoulos, Travis Biechele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0603523104"}], "href": "https://doi.org/10.1073/pnas.0603523104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17517621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17517621"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yulian Zhou, Jeremy Nathans "}, {"type": "b", "children": [{"type": "t", "text": "Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2014.08.018"}], "href": "https://doi.org/10.1016/j.devcel.2014.08.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25373781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25373781"}]}]}]}
Synonyms	ADCAD2, STHAG7
Proteins	LRP6_HUMAN
NCBI Gene ID	4040
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LRP6 has 11,766 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 133 datasets.

Click the + buttons to view associations for LRP6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LRP6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by LRP6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LRP6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LRP6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of LRP6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LRP6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of LRP6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LRP6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving LRP6 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LRP6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LRP6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LRP6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LRP6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LRP6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LRP6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with LRP6 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LRP6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LRP6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LRP6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LRP6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LRP6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LRP6 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LRP6 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LRP6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LRP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LRP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LRP6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LRP6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LRP6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LRP6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LRP6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LRP6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LRP6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LRP6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LRP6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LRP6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LRP6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LRP6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LRP6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LRP6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LRP6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.