U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 4040, updated on 11-Apr-2024

Summary

Go to the top of the page Help
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; AllianceGenome:HGNC:6698
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
12p13.2
Exon count:
29
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (12116025..12267044, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (11985150..12136111, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (12268959..12419978, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:12210407-12211072 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:12211073-12211736 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:12216444-12216992 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:12222531-12222710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6009 Neighboring gene BCL2 like 14 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:12225917-12226604 Neighboring gene Sharpr-MPRA regulatory region 14349 Neighboring gene Sharpr-MPRA regulatory region 8243 Neighboring gene microRNA 1244-4 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:12283961-12284161 Neighboring gene prothymosin alpha pseudogene 9 Neighboring gene ribosomal protein L21 pseudogene 100 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4250 Neighboring gene Sharpr-MPRA regulatory region 15090 Neighboring gene mortality factor 4 like 1 pseudogene 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:12368521-12369020 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:12381345-12381845 Neighboring gene RNA, U6 small nuclear 545, pseudogene Neighboring gene ubiquitin-conjugating enzyme E2 variant 1-like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:12416308-12416808 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4251 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:12419985-12420621 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:12436705-12437246 Neighboring gene RNA, U6 small nuclear 318, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:12478241-12478741 Neighboring gene MANSC domain containing 1 Neighboring gene ribosomal protein L23a pseudogene 66

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Overexpression of circRNAs LRP6 in gestational diabetes mellitus predicts foetal malformation and intrauterine death. Hao H, et al. Endocrinol Diabetes Nutr (Engl Ed), 2023 Feb. PMID 36925229
  2. A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease. Jones ME, et al. Sci Adv, 2023 Jan 13. PMID 36638182, Free PMC Article
  3. Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies. Kantaputra P, et al. Arch Oral Biol, 2022 Oct. PMID 35961235
  4. An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a Caucasian family. Puente N, et al. Osteoporos Int, 2022 Nov. PMID 35840698, Free PMC Article
  5. circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis. Yu Y, et al. Int J Oncol, 2022 Apr. PMID 35211755, Free PMC Article

See all (272) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The inhibition of YTHDF3/m[6]A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.
    Title: The inhibition of YTHDF3/m(6)A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.
  2. LRP5-/6 gene polymorphisms and its association with risk of abnormal bone mass in postmenopausal women.
    Title: LRP5-/6 gene polymorphisms and its association with risk of abnormal bone mass in postmenopausal women.
  3. Overexpression of circRNAs LRP6 in gestational diabetes mellitus predicts foetal malformation and intrauterine death.
    Title: Overexpression of circRNAs LRP6 in gestational diabetes mellitus predicts foetal malformation and intrauterine death.
  4. LRP6/filamentous-actin signaling facilitates osteogenic commitment in mechanically induced periodontal ligament stem cells.
    Title: LRP6/filamentous-actin signaling facilitates osteogenic commitment in mechanically induced periodontal ligament stem cells.
  5. A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease.
    Title: A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease.
  6. An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a Caucasian family.
    Title: An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a Caucasian family.
  7. Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.
    Title: Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.
  8. Variants in the Wnt co-receptor LRP6 are associated with familial exudative vitreoretinopathy.
    Title: Variants in the Wnt co-receptor LRP6 are associated with familial exudative vitreoretinopathy.
  9. SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/beta-catenin signaling.
    Title: SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/β-catenin signaling.
  10. circLRP6 contributes to osteosarcoma progression by regulating the miR1413p/HDAC4/HMGB1 axis.
    Title: circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis.
Submit: New GeneRIF Correction See all GeneRIFs (191)

Phenotypes

Go to the top of the page Help

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

EBI GWAS Catalog

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

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ90062, FLJ90421

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables Wnt receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables Wnt-protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables Wnt-protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables Wnt-protein binding TAS
Traceable Author Statement
more info
 PubMed 
enables coreceptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables coreceptor activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables frizzled binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables kinase inhibitor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables low-density lipoprotein particle receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
NOT enables toxin transmembrane transporter activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables toxin transmembrane transporter activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in Wnt signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in canonical Wnt signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within canonical Wnt signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
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 canonical Wnt signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in cell-cell adhesion IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to cholesterol IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in dopaminergic neuron differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in midbrain dopaminergic neuron differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of smooth muscle cell apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in neural crest cell differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in neural crest formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cytosolic calcium ion concentration 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 protein localization to plasma membrane IPI
Inferred from Physical Interaction
more info
 PubMed 
involved_in response to peptide hormone IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
colocalizes_with Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Wnt signalosome IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Wnt signalosome NAS
Non-traceable Author Statement
more info
 PubMed 
part_of Wnt-Frizzled-LRP5/6 complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Wnt-Frizzled-LRP5/6 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of Wnt-Frizzled-LRP5/6 complex TAS
Traceable Author Statement
more info
 PubMed 
colocalizes_with caveola IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
colocalizes_with early endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in early endosome membrane TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
more info
  

General protein information

Go to the top of the page Help
Preferred Names
low-density lipoprotein receptor-related protein 6
Names
LRP-6

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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

  1. NG_016168.2 RefSeqGene

    Range
    4834..155853
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001414244.1 → NP_001401173.1  low-density lipoprotein receptor-related protein 6 isoform a precursor

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  2. NM_001414245.1 → NP_001401174.1  low-density lipoprotein receptor-related protein 6 isoform b precursor

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603
    UniProtKB/Swiss-Prot
    O75581, Q17RZ2

  3. NM_001414246.1 → NP_001401175.1  low-density lipoprotein receptor-related protein 6 isoform c

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603
    UniProtKB/TrEMBL
    F5H7J9
    Related
    ENSP00000442472.1, ENST00000543091.1

  4. NM_001414247.1 → NP_001401176.1  low-density lipoprotein receptor-related protein 6 isoform d

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  5. NM_001414248.1 → NP_001401177.1  low-density lipoprotein receptor-related protein 6 isoform e precursor

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  6. NM_001414249.1 → NP_001401178.1  low-density lipoprotein receptor-related protein 6 isoform f precursor

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  7. NM_001414250.1 → NP_001401179.1  low-density lipoprotein receptor-related protein 6 isoform g precursor

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  8. NM_001414251.1 → NP_001401180.1  low-density lipoprotein receptor-related protein 6 isoform h

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  9. NM_001414252.1 → NP_001401181.1  low-density lipoprotein receptor-related protein 6 isoform i

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  10. NM_001414253.1 → NP_001401182.1  low-density lipoprotein receptor-related protein 6 isoform i

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  11. NM_001414254.1 → NP_001401183.1  low-density lipoprotein receptor-related protein 6 isoform i

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  12. NM_001414255.1 → NP_001401184.1  low-density lipoprotein receptor-related protein 6 isoform j

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

  13. NM_002336.3 → NP_002327.2  low-density lipoprotein receptor-related protein 6 isoform b 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, Q17RZ2
    UniProtKB/TrEMBL
    B7ZLD0
    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

RNA

  1. NR_182264.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC007537, AC007621, KF455603

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    12116025..12267044 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047428844.1 → XP_047284800.1  low-density lipoprotein receptor-related protein 6 isoform X1

RNA

  1. XR_002957325.2 RNA Sequence

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_011332696.1 Reference GRCh38.p14 PATCHES

    Range
    85023..236042 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054331699.1 → XP_054187674.1  low-density lipoprotein receptor-related protein 6 isoform X1

RNA

  1. XR_008485729.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    11985150..12136111 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372051.1 → XP_054228026.1  low-density lipoprotein receptor-related protein 6 isoform X1

RNA

  1. XR_008488585.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75581.2 GenPept UniProtKB/Swiss-Prot:O75581

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous