SORCS2 Gene

Name	sortilin-related VPS10 domain containing receptor 2
Description	This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSORCS2 has emerged as a critical mediator in neurodegenerative processes, with immunohistochemical studies in amyotrophic lateral sclerosis revealing that nearly all Bunina bodies in affected anterior horn cells are strongly positive for this receptor, suggesting its involvement in motor neuron pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, biochemical and ultrastructural analyses of VPS10P‐domain receptors have demonstrated that SORCS2, along with its family members, exists in both stable monomeric and dimeric forms—with glycosylation patterns governing its oligomeric state and, consequently, ligand specificity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \n \nGenomic studies further implicate SORCS2 in pharmacogenetic variability and potentially in stress‐related disorders. Genome‐wide association analyses have identified an intronic variant in SORCS2 (rs73208473) that is linked to significantly decreased atazanavir exposure in hair"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", a finding that was subsequently corroborated by dose‐adjusted plasma concentration studies in African Americans."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Additionally, while the genetic determinants underlying alcohol withdrawal remain to be fully elucidated, emerging evidence points to a possible role for SORCS2 as a candidate risk factor in stress‐related physiological responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n \n \nAt the cellular level, SORCS2 functions as a key sorting receptor that sustains plasma membrane expression of the neuronal amino acid transporter EAAT3. This activity promotes cysteine uptake, which is essential for glutathione synthesis and thereby protects neurons from oxidative stress and epilepsy‐induced cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, loss of SORCS2 has been associated with elevated levels of DNA double‐strand breaks, linking it to defective DNA repair mechanisms in neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Complementing these protective roles, alternative splicing of SORCS2 generates a spectrum of isoforms with variable intracellular domains that modulate its interactions with adaptor proteins and motor complexes, thereby impacting brain‐derived neurotrophic factor signaling, neuronal morphology, and plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fumiaki Mori, Yasuo Miki, Kunikazu Tanji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin-related receptor CNS expressed 2 (SorCS2) is localized to Bunina bodies in amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2015.09.030"}], "href": "https://doi.org/10.1016/j.neulet.2015.09.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26420026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26420026"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dovile Januliene, Arulmani Manavalan, Peter Lund Ovesen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hidden Twins: SorCS Neuroreceptors Form Stable Dimers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2017.08.006"}], "href": "https://doi.org/10.1016/j.jmb.2017.08.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28827148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28827148"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bani Tamraz, Yong Huang, Audrey L French, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cpt.1014"}], "href": "https://doi.org/10.1002/cpt.1014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29315502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29315502"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bani Tamraz, Yong Huang, Audrey L French, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Pharmacogenetic Markers With Atazanavir Exposure in HIV-Infected Women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cpt.1605"}], "href": "https://doi.org/10.1002/cpt.1605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31562781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31562781"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andrew H Smith, Peter L Ovesen, Sune Skeldal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Risk Locus Identification Ties Alcohol Withdrawal Symptoms to SORCS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acer.13890"}], "href": "https://doi.org/10.1111/acer.13890"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30252935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30252935"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anna R Malik, Kinga Szydlowska, Karolina Nizinska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.02.027"}], "href": "https://doi.org/10.1016/j.celrep.2019.02.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30840898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30840898"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Katerina O Gospodinova, Ditte Olsen, Mathias Kaas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Neurobiol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10571-021-01163-7"}], "href": "https://doi.org/10.1007/s10571-021-01163-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34741697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34741697"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sune Skeldal, Lasse Frank Voss, Jonas Lende, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing regulates adaptor protein binding, trafficking, and activity of the Vps10p domain receptor SorCS2 in neuronal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.105102"}], "href": "https://doi.org/10.1016/j.jbc.2023.105102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37507021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37507021"}]}]}]}
Proteins	SORC2_HUMAN
NCBI Gene ID	57537
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SORCS2 has 4,909 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for SORCS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SORCS2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SORCS2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SORCS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SORCS2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SORCS2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SORCS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SORCS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SORCS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SORCS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SORCS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SORCS2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SORCS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SORCS2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SORCS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SORCS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SORCS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SORCS2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SORCS2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SORCS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SORCS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SORCS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SORCS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SORCS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SORCS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SORCS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SORCS2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SORCS2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SORCS2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SORCS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SORCS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SORCS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SORCS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SORCS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SORCS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SORCS2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SORCS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SORCS2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SORCS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SORCS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SORCS2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing SORCS2 from the GeneSigDB Published Gene Signatures dataset.