CLSTN3 Gene

HGNC Family	Cadherins
Name	calsyntenin 3
Description	Enables cell-cell adhesion mediator activity and neurexin family protein binding activity. Involved in L-ascorbic acid metabolic process and regulation of synapse assembly. Predicted to be located in several cellular components, including Golgi membrane; dendrite; and postsynaptic density. Predicted to be part of protein-containing complex. Predicted to be active in several cellular components, including GABA-ergic synapse; lipid droplet; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLSTN3, a member of the calsyntenin family of cadherin‐related proteins, plays multifaceted roles in the nervous system. At synapses, CLSTN3 is expressed postsynaptically where it directly binds neurexin—via its LNS and cadherin domains—to trigger presynaptic differentiation and organize trans‐synaptic complexes. This synaptic organizer function is essential for the proper development and balance of excitatory and inhibitory synapses, as demonstrated by cerebellar studies in which acute deletion of CLSTN3 reduced inhibitory synapse formation while enhancing excitatory parallel‐fiber contacts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in synaptogenesis, neuronal CLSTN3 contributes to systemic energy and bone homeostasis. Global knockout studies have revealed that loss of CLSTN3 leads to decreased body mass with improved leptin sensitivity, increased energy expenditure, and reduced cortical bone mass – effects attributable to its neuronal expression rather than to direct actions in bone‐forming cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, mutations in CLSTN3 have been genetically associated with hyperaldosteronism, suggesting that alteration in this gene’s function may contribute to endocrine imbalances."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of neurodegenerative pathology, aberrant processing of CLSTN3 has been implicated in Alzheimer disease. Proteolytic cleavage yields a C‐terminal fragment that accumulates in dystrophic neurites surrounding β‐amyloid plaques, wherein it accelerates neuronal death. Such findings indicate that, under pathologic conditions, dysregulation of CLSTN3 processing may exacerbate neuronal damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, environmental factors that perturb normal neurodevelopment can alter the expression of calsyntenins. For example, perinatal exposure to lead has been shown to differentially affect CLSTN isoform expression – with CLSTN3 being significantly upregulated in key brain regions – a change that may contribute to subsequent cognitive deficits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhuoyang Lu, Yun Wang, Fang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calsyntenin-3 molecular architecture and interaction with neurexin 1α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.606806"}], "href": "https://doi.org/10.1074/jbc.M114.606806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25352602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25352602"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhihui Liu, Man Jiang, Kif Liakath-Ali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of Calsyntenin-3, an atypical cadherin, suppresses inhibitory synapses but increases excitatory parallel-fiber synapses in cerebellum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.70664"}], "href": "https://doi.org/10.7554/eLife.70664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35420982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35420982"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sung-Jin Kim, Yong Taek Jeong, Se Rok Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neural regulation of energy and bone homeostasis by the synaptic adhesion molecule Calsyntenin-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s12276-020-0419-8"}], "href": "https://doi.org/10.1038/s12276-020-0419-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32382066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32382066"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "L G Perez-Rivas, Y Rhayem, S Sabrautzki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic characterization of a mouse line with primary aldosteronism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Endocrinol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JME-16-0200"}], "href": "https://doi.org/10.1530/JME-16-0200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27965370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27965370"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yoko Uchida, Fujiya Gomi, Shigeo Murayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calsyntenin-3 C-terminal fragment accumulates in dystrophic neurites surrounding aβ plaques in tg2576 mouse and Alzheimer disease brains: its neurotoxic role in mediating dystrophic neurite formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.01.014"}], "href": "https://doi.org/10.1016/j.ajpath.2013.01.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23499467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23499467"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yoko Uchida, Fujiya Gomi "}, {"type": "b", "children": [{"type": "t", "text": "The role of calsyntenin-3 in dystrophic neurite formation in Alzheimer's disease brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Geriatr Gerontol Int (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ggi.12737"}], "href": "https://doi.org/10.1111/ggi.12737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27018282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27018282"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ning Li, Shuai Cao, Zengli Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Perinatal Lead Exposure Alters Calsyntenin-2 and Calsyntenin-3 Expression in the Hippocampus and Causes Learning Deficits in Mice Post-weaning."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Trace Elem Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12011-020-02241-5"}], "href": "https://doi.org/10.1007/s12011-020-02241-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32557100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32557100"}]}]}]}
Synonyms	ALCBETA, CDHR14, CSTN3
Proteins	CSTN3_HUMAN
NCBI Gene ID	9746
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLSTN3 has 5,918 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 110 datasets.

Click the + buttons to view associations for CLSTN3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLSTN3 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLSTN3 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 CLSTN3 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 CLSTN3 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 CLSTN3 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 CLSTN3 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 CLSTN3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CLSTN3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLSTN3 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 CLSTN3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CLSTN3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLSTN3 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 CLSTN3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CLSTN3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLSTN3 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 CLSTN3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLSTN3 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 CLSTN3 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 CLSTN3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLSTN3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLSTN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLSTN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLSTN3 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 CLSTN3 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 CLSTN3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLSTN3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CLSTN3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CLSTN3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLSTN3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CLSTN3 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 CLSTN3 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 CLSTN3 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 CLSTN3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLSTN3 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 CLSTN3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLSTN3 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 CLSTN3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CLSTN3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CLSTN3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CLSTN3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CLSTN3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.