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

    Gene ID: 4040, updated on 26-Nov-2024

    Summary

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    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
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    Genomic context

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    See LRP6 in Genome Data Viewer
    Location:
    12p13.2
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (12116025..12267044, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (11985150..12136111, complement)
    RS_2024_09 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

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. A novel sLRP6E1E2 inhibits canonical Wnt signaling, epithelial-to-mesenchymal transition, and induces mitochondria-dependent apoptosis in lung cancer. Lee JS, et al. PLoS One, 2012. PMID 22606268, Free PMC Article
    2. Functional analysis LRP6 novel mutations in patients with coronary artery disease. Xu Y, et al. PLoS One, 2014. PMID 24427284, Free PMC Article
    3. Downregulated low-density lipoprotein receptor-related protein 6 induces the maldevelopment of extravillous trophoblast via Wnt/β-catenin signaling pathway. Yu X, et al. Mol Cell Probes, 2019 Apr. PMID 30684559
    4. Effect of pantoprazole on human gastric adenocarcinoma SGC7901 cells through regulation of phospho‑LRP6 expression in Wnt/β-catenin signaling. Shen W, et al. Oncol Rep, 2013 Aug. PMID 23754096
    5. Rare nonconservative LRP6 mutations are associated with metabolic syndrome. Singh R, et al. Hum Mutat, 2013 Sep. PMID 23703864, Free PMC Article

    See all (275) 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

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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
    		not available
    Tooth agenesis, selective, 7
    MedGen: C4225231 OMIM: 616724 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

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

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 
    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 chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dopaminergic neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in endocytosis IEA
    Inferred from Electronic Annotation
    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
    		  
    involved_in transmembrane transport 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
    		  
    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

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

    NCBI Reference Sequences (RefSeq)

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    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_2024_08

    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.

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