MAGI1 Gene

HGNC Family	Membrane-associated guanylate kinases, Trinucleotide repeat containing (TNRC)
Name	membrane associated guanylate kinase, WW and PDZ domain containing 1
Description	The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAGI1 is a multidomain scaffolding protein that plays a central role in maintaining cell‐cell adhesion and cytoskeletal organization in a variety of tissues. In epithelial and neural cells, MAGI1 localizes at tight and adherens junctions where it interacts with proteins such as actin-bundling molecules (e.g. synaptopodin, α‐actinin-4) and junctional components like VE-cadherin and N-cadherin–β-catenin complexes. Through these interactions, it facilitates Rap1 activation upon cell–cell contact and regulates the presentation of signaling ligands like Dll1 that are important for Notch signaling during neural development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of viral oncogenesis, MAGI1 is a key target of high‐risk human papillomavirus (HPV) E6 proteins. Binding of E6 to the PDZ domains of MAGI1 results in its proteasomal degradation and/or caspase-mediated cleavage during apoptosis. These events disrupt tight junction integrity and promote an environment favorable for viral persistence and tumor progression. Detailed structural studies, including analysis of dynamic changes in the PDZ domains and in silico docking of E6 variants, have deepened our understanding of the molecular determinants governing these interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMAGI1 also contributes significantly to kidney cell function. In podocytes, MAGI1 interacts with novel binding partners—including a coiled-coil protein (MASCOT) and the adhesion molecule sdk-1—to help organize the slit diaphragm and stabilize the actin cytoskeleton. Alterations in these interactions have been linked to glomerular diseases such as focal segmental glomerulosclerosis, and emerging evidence points to a role for MAGI1 in diabetic nephropathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn endothelial cells, MAGI1 is responsive to fluid shear stress where its expression is increased, thereby promoting proper endothelial alignment and nitric oxide (NO) production via enhanced eNOS phosphorylation. Through its influence on kinases such as PKA, AMPK, and CaMKII, MAGI1 helps maintain vascular homeostasis by modulating signaling events that underpin endothelial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe tumor suppressor functions of MAGI1 have been documented in several cancer types. In renal cell carcinoma and estrogen receptor–positive breast cancers, reduced MAGI1 expression correlates with enhanced invasiveness and altered cell adhesion, while in T-cell leukemias lower levels of MAGI1 are associated with augmented Akt and MEK signaling. In these malignancies, diminished MAGI1 impairs the stability of complexes that normally inhibit oncogenic pathways, contributing to increased genomic instability and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its regulatory roles in cell–cell adhesion and signaling, genetic studies have implicated MAGI1 in disease susceptibility. Variants near or within MAGI1 are associated with conditions such as adolescent idiopathic scoliosis, ocular sarcoidosis, and alterations in tight junction integrity observed in microscopic colitis, underlining its importance in both structural and immunological contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and post-translational modifications of MAGI1 further modulate its function. The protein undergoes caspase-dependent cleavage during apoptosis—a process that disrupts its junctional associations—and detailed biophysical analyses have revealed that specific residues in its WW domains are critical for mediating both homotypic and heterotypic protein interactions. These insights help explain how MAGI1’s conformation and integrity are maintained under physiological and pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Atsuko Sakurai, Shigetomo Fukuhara, Akiko Yamagishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin-mediated cell adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e05-07-0647"}], "href": "https://doi.org/10.1091/mbc.e05-07-0647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16339077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16339077"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kevin M Patrie, Andrew J Drescher, Ajith Welihinda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203072200"}], "href": "https://doi.org/10.1074/jbc.M203072200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12042308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12042308"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eri Mizuhara, Tomoya Nakatani, Yasuko Minaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500375200"}], "href": "https://doi.org/10.1074/jbc.M500375200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15908431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15908431"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Abimbola Olayinka Kolawole, Priyanka Sharma, Ran Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PDZ1 and PDZ3 domains of MAGI-1 regulate the eight-exon isoform of the coxsackievirus and adenovirus receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01138-12"}], "href": "https://doi.org/10.1128/JVI.01138-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22718816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22718816"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christian Kranjec, Lawrence Banks "}, {"type": "b", "children": [{"type": "t", "text": "A systematic analysis of human papillomavirus (HPV) E6 PDZ substrates identifies MAGI-1 as a major target of HPV type 16 (HPV-16) and HPV-18 whose loss accompanies disruption of tight junctions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01756-10"}], "href": "https://doi.org/10.1128/JVI.01756-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21123374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21123374"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lietta Nicolaides, Clare Davy, Kenneth Raj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.virol.2011.03.017"}], "href": "https://doi.org/10.1016/j.virol.2011.03.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21489588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21489588"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sebastian Charbonnier, Yves Nominé, Juan Ramírez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MAGI1 mediates tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-019-01562-8"}], "href": "https://doi.org/10.1007/s10495-019-01562-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31352641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31352641"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Diala Kantar, Emilie Bousquet Mur, Maicol Mancini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-85056-1"}], "href": "https://doi.org/10.1038/s41598-021-85056-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33707576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33707576"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Takashi Kozakai, Masahiko Takahashi, Masaya Higuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Hematol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12185-017-2359-1"}], "href": "https://doi.org/10.1007/s12185-017-2359-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29043551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29043551"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Janine Wörthmüller, Simona Disler, Sylvain Pradervand, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-006-0579-6"}], "href": "https://doi.org/10.1007/s10495-006-0579-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17191119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17191119"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Satoshi Ohnishi, Naoya Tochio, Tadashi Tomizawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1110/ps.035329.108"}], "href": "https://doi.org/10.1110/ps.035329.108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18562638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18562638"}]}]}]}
Synonyms	MAGI1D, AIP-3, AIP3, WWP3, MAGI-1, BAIAP1, TNRC19
Proteins	MAGI1_HUMAN
NCBI Gene ID	9223
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAGI1 has 6,131 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 127 datasets.

Click the + buttons to view associations for MAGI1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAGI1 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 MAGI1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAGI1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAGI1 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 MAGI1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAGI1 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 MAGI1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MAGI1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MAGI1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAGI1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MAGI1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAGI1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAGI1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAGI1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MAGI1 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 MAGI1 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 MAGI1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 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 MAGI1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAGI1 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 MAGI1 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 MAGI1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAGI1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.