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    SORCS3 sortilin related VPS10 domain containing receptor 3 [ Homo sapiens (human) ]

    Gene ID: 22986, updated on 27-Nov-2024

    Summary

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    Official Symbol
    SORCS3provided by HGNC
    Official Full Name
    sortilin related VPS10 domain containing receptor 3provided by HGNC
    Primary source
    HGNC:HGNC:16699
    See related
    Ensembl:ENSG00000156395 MIM:606285; AllianceGenome:HGNC:16699
    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
    SORCS
    Summary
    This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]
    Expression
    Biased expression in brain (RPKM 4.8), adrenal (RPKM 1.2) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See SORCS3 in Genome Data Viewer
    Location:
    10q25.1
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (104641290..105265242)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (105529365..106155464)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (106401048..107025000)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:106240617-106241118 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:106241119-106241618 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:106267772-106267962 Neighboring gene long intergenic non-protein coding RNA 2620 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:106293232-106293744 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:106293745-106294257 Neighboring gene uncharacterized LOC105378464 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:106440811-106441310 Neighboring gene SORCS3 antisense RNA 1 Neighboring gene NANOG hESC enhancer GRCh37_chr10:106494760-106495717 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:106568733-106569932 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:106827987-106829186 Neighboring gene uncharacterized LOC105378465 Neighboring gene uncharacterized LOC105378466 Neighboring gene uncharacterized LOC105378467

    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. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Demontis D, et al. Nat Genet, 2023 Feb. PMID 36702997, Free PMC Article
    2. The Vps10p-domain receptor family. Hermey G. Cell Mol Life Sci, 2009 Aug. PMID 19434368, Free PMC Article
    3. Independent and epistatic effects of variants in VPS10-d receptors on Alzheimer disease risk and processing of the amyloid precursor protein (APP). Reitz C, et al. Transl Psychiatry, 2013 May 14. PMID 23673467, Free PMC Article
    4. The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review. Reitz C. Mol Genet Genomics, 2015 Apr. PMID 25332075, Free PMC Article
    5. Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene. Binzer S, et al. Mult Scler, 2016 May. PMID 26362888

    See all (23) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Independent Associated SNPs at SORCS3 and Its Protein Interactors for Multiple Brain-Related Disorders and Traits.
      Title: Independent Associated SNPs at SORCS3 and Its Protein Interactors for Multiple Brain-Related Disorders and Traits.
    2. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.
      Title: Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.
    3. Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3.
      Title: Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3.
    4. SorCS3 promotes the internalization of p75(NTR) to inhibit GBM progression.
      Title: SorCS3 promotes the internalization of p75(NTR) to inhibit GBM progression.
    5. Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.
      Title: Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.
    6. First study reporting on human subjects with a SORCS3 gene defect with infantile spasms and intellectual disability; this supports the important role of SORCS3 in the central nervous system.
      Title: The SORCS3 gene is mutated in brothers with infantile spasms and intellectual disability.
    7. SORCS3 may be important in MS pathogenesis.
      Title: Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene.
    8. Here the authors have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. They found that their purified extracellular domains co-exist in stable dimeric and monomeric populations.
      Title: Hidden Twins: SorCS Neuroreceptors Form Stable Dimers.
    9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    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

    Homology

    Clone Names

    • 6330404A12Rik

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables neuropeptide receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in memory IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuropeptide signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in postsynaptic modulation of chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of long-term synaptic depression IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in postsynaptic density membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    VPS10 domain-containing receptor SorCS3
    Names
    VPS10 domain receptor protein SORCS 3 (SORCS3)

    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.

    mRNA and Protein(s)

    1. NM_014978.3 → NP_055793.1  VPS10 domain-containing receptor SorCS3 precursor

      See identical proteins and their annotated locations for NP_055793.1

      Status: REVIEWED

      Source sequence(s)
      AB028982, AL353900, BC045754
      Consensus CDS
      CCDS7558.1
      UniProtKB/Swiss-Prot
      Q5VXF9, Q9NQJ2, Q9UPU3
      UniProtKB/TrEMBL
      Q17R88
      Related
      ENSP00000358715.3, ENST00000369701.8
      Conserved Domains (4) summary
      smart00602
      Location:219 → 817
      VPS10; VPS10 domain
      pfam00801
      Location:831 → 904
      PKD; PKD domain
      pfam12300
      Location:73 → 184
      DUF3628; Protein of unknown function (DUF3628)
      pfam15901
      Location:665 → 817
      Sortilin_C; Sortilin, neurotensin receptor 3, C-terminal

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      104641290..105265242
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011539542.2 → XP_011537844.1  VPS10 domain-containing receptor SorCS3 isoform X1

      Conserved Domains (3) summary
      smart00602
      Location:1 → 461
      VPS10; VPS10 domain
      pfam00801
      Location:475 → 548
      PKD; PKD domain
      pfam15901
      Location:309 → 461
      Sortilin_C; Sortilin, neurotensin receptor 3, C-terminal

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      105529365..106155464
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054365273.1 → XP_054221248.1  VPS10 domain-containing receptor SorCS3 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UPU3.2 GenPept UniProtKB/Swiss-Prot:Q9UPU3

    Gene LinkOut

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

    Other Literature Sources
    Chemical Information
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