SYNE3 Gene

Name	spectrin repeat containing, nuclear envelope family member 3
Description	Enables actin filament binding activity and cytoskeleton-nuclear membrane anchor activity. Involved in cytoskeleton organization; establishment of protein localization to membrane; and regulation of cell shape. Located in nuclear membrane. Part of meiotic nuclear membrane microtubule tethering complex. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSYNE3 encodes nesprin‐3, a critical component of the linker of nucleoskeleton and cytoskeleton (LINC) complex that spans the outer nuclear envelope to physically couple the nucleus with the cell’s cytoskeleton. Nesprin‐3 employs its conserved C‐terminal KASH domain to interact with proteins such as torsinA—whose mutation is linked to early‐onset torsion dystonia—and to establish connections via plectin with intermediate filaments, thereby influencing the spatial distribution of cytoskeletal elements and mediating nuclear positioning and movement"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "<br><br>\nIn vascular endothelial cells, nesprin‐3 plays an instrumental role in mechanotransduction. It is robustly expressed at the nuclear envelope of human aortic endothelial cells, where it governs cell morphology by organizing the perinuclear cytoskeleton and ensuring the proper attachment of the centrosome to the nuclear envelope. These functions are essential for the polarization and migratory response to hemodynamic forces, indicating that nesprin‐3 is a key mediator in flow‐induced cellular reorganization and directional movement"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "<br><br>\nIn the context of cancer biology, particularly lung adenocarcinoma, nesprin‐3 emerges as a pivotal regulator of tumor cell migration. Studies reveal that SPAG4 acts as a positive regulator of nesprin‐3 by modulating its expression and subcellular localization, thereby facilitating cell motility and metastasis. Complementary high‐resolution structural analyses of SUN2–KASH peptide complexes further detail the unique binding modes and molecular interactions that underpin the integration of nesprin‐3 within the LINC complex, suggesting that variations in these interactions may have regulatory implications for both normal and disease‐associated cellular dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Flávia C Nery, Juan Zeng, Brian P Niland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.029454"}], "href": "https://doi.org/10.1242/jcs.029454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18827015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18827015"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Liwei Liao, Longshan Zhang, Mi Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression profile of SYNE3 and bioinformatic analysis of its prognostic value and functions in tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-020-02521-7"}], "href": "https://doi.org/10.1186/s12967-020-02521-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32948197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32948197"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Joshua T Morgan, Emily R Pfeiffer, Twanda L Thirkill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-04-0287"}], "href": "https://doi.org/10.1091/mbc.E11-04-0287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21937718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21937718"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ying Ji, Jinquan Jiang, Lihua Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sperm‑associated antigen 4 (SPAG4) as a new cancer marker interacts with Nesprin3 to regulate cell migration in lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6473"}], "href": "https://doi.org/10.3892/or.2018.6473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29901114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29901114"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Victor E Cruz, F Esra Demircioglu, Thomas U Schwartz "}, {"type": "b", "children": [{"type": "t", "text": "Structural Analysis of Different LINC Complexes Reveals Distinct Binding Modes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2020.09.019"}], "href": "https://doi.org/10.1016/j.jmb.2020.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33058875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33058875"}]}]}]}
Synonyms	NESP3, NET53, KASH3, LINC00341, C14ORF49
Proteins	SYNE3_HUMAN
NCBI Gene ID	161176
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SYNE3 has 5,784 functional associations with biological entities spanning 9 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, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for SYNE3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SYNE3 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 SYNE3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 SYNE3 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 SYNE3 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 SYNE3 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 SYNE3 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 SYNE3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SYNE3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SYNE3 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 SYNE3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SYNE3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SYNE3 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 SYNE3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SYNE3 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 SYNE3 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 SYNE3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SYNE3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SYNE3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SYNE3 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 SYNE3 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 SYNE3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SYNE3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SYNE3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SYNE3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SYNE3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SYNE3 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 SYNE3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SYNE3 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SYNE3 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 SYNE3 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 SYNE3 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 SYNE3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SYNE3 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 SYNE3 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 SYNE3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SYNE3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GAD Gene-Disease Associations	diseases associated with SYNE3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SYNE3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SYNE3 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 SYNE3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SYNE3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.