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

Summary

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

Location:: 10q25.1

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (104641290..105265242)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (105529365..106155464)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (106401048..107025000)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
SorCS3 promotes the internalization of p75(NTR) to inhibit GBM progression.
Title: SorCS3 promotes the internalization of p75(NTR) to inhibit GBM progression.
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.
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.
SORCS3 may be important in MS pathogenesis.
Title: Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene.
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.
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.
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

WI-11152 (e-PCR)
- UniSTS:46345

D10S266 (e-PCR)
- UniSTS:147984

D10S20 (e-PCR)
- UniSTS:147997

SHGC-155953 (e-PCR)
- UniSTS:182314

D10S467 (e-PCR), detects polymorphism
- UniSTS:148098

SHGC-106916 (e-PCR)
- UniSTS:182170

SHGC-145786 (e-PCR)
- UniSTS:174791

G59484 (e-PCR)
- UniSTS:136648

D10S1671 (e-PCR), detects polymorphism
- UniSTS:19420

D10S1264 (e-PCR), detects polymorphism
- UniSTS:17893

D10S2212 (e-PCR)
- UniSTS:30441

SHGC-147240 (e-PCR)
- UniSTS:172778

RH93114 (e-PCR)
- UniSTS:92656

RH122394 (e-PCR)
- UniSTS:138490

SHGC-145871 (e-PCR)
- UniSTS:174846

D10S2469 (e-PCR)
- UniSTS:76543

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)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

104641290..105265242

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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