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    LRP8 LDL receptor related protein 8 [ Homo sapiens (human) ]

    Gene ID: 7804, updated on 28-Oct-2024

    Summary

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    Official Symbol
    LRP8provided by HGNC
    Official Full Name
    LDL receptor related protein 8provided by HGNC
    Primary source
    HGNC:HGNC:6700
    See related
    Ensembl:ENSG00000157193 MIM:602600; AllianceGenome:HGNC:6700
    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
    MCI1; LRP-8; APOER2; HSZ75190
    Summary
    This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]
    Expression
    Biased expression in thyroid (RPKM 23.6), testis (RPKM 14.4) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LRP8 in Genome Data Viewer
    Location:
    1p32.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (53242364..53328070, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (53123827..53210280, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (53708036..53793742, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:53685707-53686208 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 904 Neighboring gene CXXC motif containing zinc binding protein Neighboring gene CZIB divergent transcript Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:53703843-53704484 Neighboring gene mago homolog, exon junction complex subunit Neighboring gene MAGOH divergent transcript Neighboring gene uncharacterized LOC105378728 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:53719456-53719559 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:53719749-53719966 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53736648-53737148 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1044 Neighboring gene uncharacterized LOC105378726 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53760223-53760764 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53760765-53761305 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53773439-53774256 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53774971-53775472 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53775473-53775972 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53777583-53778082 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53784579-53785264 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53785265-53785950 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:53790955-53791710 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 905 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 906 Neighboring gene Sharpr-MPRA regulatory region 13758 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1045 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 907 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 908 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1046 Neighboring gene uncharacterized LOC105378731 Neighboring gene LRP8 divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:53805229-53805730 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1047 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr1:53816803-53817658 Neighboring gene long intergenic non-protein coding RNA 2812

    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 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 molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene. Shen GQ, et al. Circ Cardiovasc Genet, 2014 Aug. PMID 24867879, Free PMC Article
    2. Additive effect of LRP8/APOER2 R952Q variant to APOE epsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein E concentration and the risk of myocardial infarction: a case-control study. Martinelli N, et al. BMC Med Genet, 2009 May 13. PMID 19439088, Free PMC Article
    3. Reduced expression of apolipoprotein E receptor type 2 in peripheral blood lymphocytes from patients with major depressive disorder. Suzuki K, et al. Prog Neuropsychopharmacol Biol Psychiatry, 2010 Aug 16. PMID 20493228
    4. Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study. Dolley G, et al. Mol Genet Metab, 2011 Apr. PMID 21316997
    5. Similarities and differences in structure, expression, and functions of VLDLR and ApoER2. Reddy SS, et al. Mol Neurodegener, 2011 May 9. PMID 21554715, Free PMC Article

    See all (140) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses.
      Title: OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses.
    2. LRP8 promotes tumorigenesis in ovarian cancer through inhibiting p53 signaling.
      Title: LRP8 promotes tumorigenesis in ovarian cancer through inhibiting p53 signaling.
    3. Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling.
      Title: Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling.
    4. The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.
      Title: The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.
    5. MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/beta-catenin axis.
      Title: MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis.
    6. ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer's disease.
      Title: ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer's disease.
    7. LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma.
      Title: LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma.
    8. LRP8, modulated by miR-1262, promotes tumour progression and forecasts the prognosis of patients in breast cancer.
      Title: LRP8, modulated by miR-1262, promotes tumour progression and forecasts the prognosis of patients in breast cancer.
    9. Human APOER2 Isoforms Have Differential Cleavage Events and Synaptic Properties.
      Title: Human APOER2 Isoforms Have Differential Cleavage Events and Synaptic Properties.
    10. miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8.
      Title: miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8.
    Submit: New GeneRIF Correction See all GeneRIFs (66)

    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
    Myocardial infarction, susceptibility to
    MedGen: C1832662 OMIM: 608446 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women's Health Initiative SHARe Study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 amyloid-beta binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables apolipoprotein binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium-dependent protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cargo receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables high-density lipoprotein particle binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables kinesin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables low-density lipoprotein particle receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables reelin receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables transmembrane signaling receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables very-low-density lipoprotein particle receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ammon gyrus development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cellular response to cholesterol IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cytokine-mediated signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in dendrite morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endocytosis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in layer formation in cerebral cortex IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in layer formation in cerebral cortex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in lipid metabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in modulation of chemical synaptic transmission ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of dendrite development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of dendritic spine morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in proteolysis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in reelin-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of innate immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in retinoid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in ventral spinal cord development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in Schaffer collateral - CA1 synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in caveola IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in caveola IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cell surface IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in dendrite IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular space IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane HDA PubMed 
    located_in membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    part_of microtubule associated complex IEA
    Inferred from Electronic Annotation
    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
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynaptic density membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of receptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    low-density lipoprotein receptor-related protein 8
    Names
    ApoE receptor 2
    low density lipoprotein receptor-related protein 8, apolipoprotein e receptor

    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_011517.2 RefSeqGene

      Range
      5080..90786
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001018054.3 → NP_001018064.1  low-density lipoprotein receptor-related protein 8 isoform 4 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an exon in the 3' coding region but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AL355483, AL606760, BC051836, DB452432
      Consensus CDS
      CCDS30720.1
      UniProtKB/TrEMBL
      A0A590UJF9
      Related
      ENSP00000360509.2, ENST00000371454.6
      Conserved Domains (7) summary
      smart00192
      Location:85 → 117
      LDLa; Low-density lipoprotein receptor domain class A
      smart00135
      Location:489 → 531
      LY; Low-density lipoprotein-receptor YWTD domain
      smart00179
      Location:376 → 406
      EGF_CA; Calcium-binding EGF-like domain
      cd00112
      Location:47 → 81
      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 ...
      pfam00057
      Location:262 → 294
      Ldl_recept_a; Low-density lipoprotein receptor domain class A
      pfam00058
      Location:552 → 592
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:340 → 374
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    2. NM_004631.5 → NP_004622.2  low-density lipoprotein receptor-related protein 8 isoform 1 precursor

      See identical proteins and their annotated locations for NP_004622.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL355483, AL606760, BC006443, D50678, DR002432
      Consensus CDS
      CCDS578.1
      UniProtKB/Swiss-Prot
      B1AMT6, B1AMT7, B1AMT8, O14968, Q14114, Q86V27, Q99876, Q9BR78
      UniProtKB/TrEMBL
      A0A590UJ57
      Related
      ENSP00000303634.6, ENST00000306052.12
      Conserved Domains (7) summary
      smart00192
      Location:85 → 117
      LDLa; Low-density lipoprotein receptor domain class A
      smart00135
      Location:489 → 531
      LY; Low-density lipoprotein-receptor YWTD domain
      smart00179
      Location:376 → 406
      EGF_CA; Calcium-binding EGF-like domain
      cd00112
      Location:47 → 81
      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 ...
      pfam00057
      Location:262 → 294
      Ldl_recept_a; Low-density lipoprotein receptor domain class A
      pfam00058
      Location:552 → 592
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:340 → 374
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    3. NM_017522.5 → NP_059992.3  low-density lipoprotein receptor-related protein 8 isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks three exons in the coding region but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AL119002, AL355483, AL606760, BC051836, BE543079, DB452432, Z75190
      Consensus CDS
      CCDS579.1
      UniProtKB/TrEMBL
      A0A590UK84
      Related
      ENSP00000346391.3, ENST00000354412.7
      Conserved Domains (7) summary
      smart00192
      Location:85 → 117
      LDLa; Low-density lipoprotein receptor domain class A
      smart00135
      Location:360 → 402
      LY; Low-density lipoprotein-receptor YWTD domain
      smart00179
      Location:247 → 277
      EGF_CA; Calcium-binding EGF-like domain
      cd00112
      Location:47 → 81
      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 ...
      pfam00057
      Location:169 → 204
      Ldl_recept_a; Low-density lipoprotein receptor domain class A
      pfam00058
      Location:423 → 463
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:211 → 245
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    4. NM_033300.4 → NP_150643.2  low-density lipoprotein receptor-related protein 8 isoform 2 precursor

      See identical proteins and their annotated locations for NP_150643.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two consecutive coding exons but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AL119002, AL355483, AL606760, BC006443, CD300289, DB455425
      Consensus CDS
      CCDS580.1
      UniProtKB/TrEMBL
      A0A590UJ98
      Related
      ENSP00000334522.2, ENST00000347547.7
      Conserved Domains (6) summary
      smart00192
      Location:85 → 117
      LDLa; Low-density lipoprotein receptor domain class A
      smart00135
      Location:319 → 361
      LY; Low-density lipoprotein-receptor YWTD domain
      smart00179
      Location:206 → 236
      EGF_CA; Calcium-binding EGF-like domain
      cd00112
      Location:47 → 81
      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:382 → 422
      Ldl_recept_b; Low-density lipoprotein receptor repeat class B
      pfam14670
      Location:170 → 204
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      53242364..53328070 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      53123827..53210280 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14114.4 GenPept UniProtKB/Swiss-Prot:Q14114

    Gene LinkOut

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