AGRN Gene

HGNC Family	Proteoglycans
Name	agrin
Description	This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Agrin is a secreted extracellular matrix proteoglycan that plays a multifaceted role in both the formation and maintenance of neuromuscular as well as non‐neuromuscular synapses. In the neuromuscular system, agrin is released by motor neurons where it binds to its muscle receptor LRP4, thereby stimulating the tyrosine kinase MuSK and initiating a signaling cascade that drives the clustering of acetylcholine receptors and the further maturation of the postsynaptic apparatus."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Mutations in the AGRN gene can compromise agrin’s ability to stabilize the neuromuscular junction, resulting in congenital myasthenic syndromes, and autoantibodies directed against agrin have been implicated in myasthenia gravis by blocking agrin-induced MuSK activation and acetylcholine receptor clustering."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, agrin serves as a key component of various basement membranes; by interacting with the dystroglycan complex, it contributes to the structural integrity and the anionic charge of the glomerular basement membrane as well as the basal lamina of the blood–brain barrier."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, agrin functions as a mechanotransducer in the extracellular matrix, modulating cellular responses to rigidity cues, and its overexpression has been linked to oncogenic signaling and tumor progression in hepatocellular carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, proteolytic cleavage of agrin by neurotrypsin plays a critical role in synaptic remodeling in the central nervous system and contributes to muscle degeneration and sarcopenia, thereby emphasizing its importance in the dynamic regulation of synaptic plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Natalie Kim, Amy L Stiegler, Thomas O Cameron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lrp4 is a receptor for Agrin and forms a complex with MuSK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.10.002"}], "href": "https://doi.org/10.1016/j.cell.2008.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18848351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18848351"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bin Zhang, Shiwen Luo, Qiang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRP4 serves as a coreceptor of agrin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2008.10.006"}], "href": "https://doi.org/10.1016/j.neuron.2008.10.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18957220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18957220"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kumiko Okada, Akane Inoue, Momoko Okada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1127142"}], "href": "https://doi.org/10.1126/science.1127142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16794080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16794080"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haitao Wu, Yisheng Lu, Chengyong Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2012.04.033"}], "href": "https://doi.org/10.1016/j.neuron.2012.04.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22794264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22794264"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Caroline Huzé, Stéphanie Bauché, Pascale Richard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an agrin mutation that causes congenital myasthenia and affects synapse function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.06.015"}], "href": "https://doi.org/10.1016/j.ajhg.2009.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19631309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19631309"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bin Zhang, Chengyong Shen, Beverly Bealmear, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoantibodies to agrin in myasthenia gravis patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0091816"}], "href": "https://doi.org/10.1371/journal.pone.0091816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24632822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24632822"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Scott J Harvey, George Jarad, Jeanette Cunningham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2007.061116"}], "href": "https://doi.org/10.2353/ajpath.2007.061116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17591961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17591961"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gesa Rascher, Arne Fischmann, Stephan Kröger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-002-0524-x"}], "href": "https://doi.org/10.1007/s00401-002-0524-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12070669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12070669"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Daniel E Michele, Rita Barresi, Motoi Kanagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature00837"}], "href": "https://doi.org/10.1038/nature00837"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12140558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12140558"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sayan Chakraborty, Manikandan Lakshmanan, Hannah L F Swa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms7184"}], "href": "https://doi.org/10.1038/ncomms7184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25630468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25630468"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Alexander Stephan, José María Mateos, Serguei V Kozlov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurotrypsin cleaves agrin locally at the synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-100008"}], "href": "https://doi.org/10.1096/fj.07-100008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18230682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18230682"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Lukas Bütikofer, Andreas Zurlinden, Marc F Bolliger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.11-191262"}], "href": "https://doi.org/10.1096/fj.11-191262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21885656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21885656"}]}]}]}
Synonyms	AGRIN, CMS8, CMSPPD
Proteins	AGRIN_HUMAN
NCBI Gene ID	375790
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AGRN has 9,215 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 131 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

AGRN 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 AGRN 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 AGRN 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 AGRN 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 RNA-seq	tissue samples with high or low expression of AGRN 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 AGRN gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving AGRN protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of AGRN 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 AGRN 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 AGRN 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 AGRN gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AGRN 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 AGRN gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AGRN protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AGRN 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 AGRN gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AGRN 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 AGRN gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with AGRN gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with AGRN gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing AGRN protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AGRN gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AGRN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AGRN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AGRN protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing AGRN protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AGRN 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 AGRN 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 AGRN gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AGRN gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AGRN gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AGRN gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AGRN 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 AGRN gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving AGRN gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving AGRN gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with AGRN 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 AGRN 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 AGRN 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 AGRN gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AGRN gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.