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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MAGI2
membrane associated guanylate kinase, WW and PDZ domain containing 2
Chromosome 7 Β· 7q21.11
NCBI Gene: 9863Ensembl: ENSG00000187391.23HGNC: HGNC:18957UniProt: B7Z4H4
100PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytoplasmsignaling receptor complex adaptor activitynegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionnephrotic syndrome 15neurodegenerative diseasenephrotic syndromefamilial idiopathic steroid-resistant nephrotic syndrome
✦AI Summary

MAGI2 is a membrane-associated guanylate kinase scaffold protein that plays critical roles in cellular architecture and signaling across multiple tissues. The protein functions as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins 1. In podocyte development, MAGI2 is a key target of the transcription factor WT1, where it regulates the WNT signaling pathway alongside BMPER and PAX2 2. MAGI2 maintains tight junction integrity in intestinal epithelial cells, with its expression being constitutively downregulated in celiac disease, affecting the expression of several tight junction-related genes 3. The protein also functions as a tumor suppressor in various cancers, with mounting evidence indicating essential roles in maintaining cell structural integrity in non-neuronal tissues 1. In breast cancer, MAGI2 interacts with CLDN6 to prevent KLF5 nuclear entry, thereby restraining SREBF1 transcription and ultimately inhibiting RAS palmitoylation-mediated oncogenic activation 4. Additionally, MAGI2 promoter hypermethylation is associated with gastric cancer progression and may serve as a prognostic biomarker 5. These diverse functions establish MAGI2 as a crucial scaffold protein involved in cellular organization, tumor suppression, and disease pathogenesis.

Sources cited
1
MAGI2 acts as scaffold molecule at synapses and functions as tumor suppressor in non-neuronal tissues
PMID: 25637633
2
MAGI2 is a WT1 target gene regulating WNT signaling pathway in podocyte development
PMID: 38810140
3
MAGI2 maintains tight junction integrity and is downregulated in celiac disease
PMID: 31921880
4
MAGI2 interacts with CLDN6 to prevent KLF5 nuclear entry and suppress breast cancer progression
PMID: 39169280
5
MAGI2 promoter hypermethylation is associated with gastric cancer and may serve as prognostic biomarker
PMID: 33530176
Disease Associationsβ“˜21
nephrotic syndrome 15Open Targets
0.63Moderate
neurodegenerative diseaseOpen Targets
0.48Moderate
nephrotic syndromeOpen Targets
0.39Weak
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.39Weak
type 2 diabetes mellitusOpen Targets
0.38Weak
smoking initiationOpen Targets
0.35Weak
lagophthalmosOpen Targets
0.32Weak
attention deficit hyperactivity disorderOpen Targets
0.32Weak
obesityOpen Targets
0.32Weak
substance abuseOpen Targets
0.32Weak
cannabis dependenceOpen Targets
0.32Weak
diabetes mellitusOpen Targets
0.31Weak
COVID-19Open Targets
0.30Weak
neuroinflammatory disorderOpen Targets
0.30Weak
Abruptio PlacentaeOpen Targets
0.29Weak
central nervous system cancerOpen Targets
0.28Weak
adverse effectOpen Targets
0.28Weak
congenital anomaly of cardiovascular systemOpen Targets
0.28Weak
poisoningOpen Targets
0.28Weak
tricuspid valve diseaseOpen Targets
0.28Weak
Nephrotic syndrome 15UniProt
Pathogenic Variants9
NM_012301.4(MAGI2):c.1390del (p.Asp464fs)Likely pathogenic
Nephrotic syndrome 15
β˜…β˜†β˜†β˜†2024β†’ Residue 464
NM_012301.4(MAGI2):c.712G>T (p.Glu238Ter)Likely pathogenic
Nephrotic syndrome 15
β˜…β˜†β˜†β˜†2024β†’ Residue 238
NM_012301.4(MAGI2):c.2269+2dupLikely pathogenic
Nephrotic syndrome 15
β˜…β˜†β˜†β˜†2024
NM_012301.4(MAGI2):c.79C>T (p.Gln27Ter)Likely pathogenic
Nephrotic syndrome 15
β˜…β˜†β˜†β˜†2024β†’ Residue 27
NM_012301.4(MAGI2):c.159_174del (p.Tyr54fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 54
NM_012301.4(MAGI2):c.147del (p.Gly50fs)Likely pathogenic
Nephrotic syndrome 15
β˜…β˜†β˜†β˜†2021β†’ Residue 50
NM_012301.4(MAGI2):c.3998del (p.Gly1333fs)Pathogenic
Nephrotic syndrome 15
β˜†β˜†β˜†β˜†2018β†’ Residue 1333
NM_012301.4(MAGI2):c.64_71del (p.Arg22fs)Pathogenic
Nephrotic syndrome 15
β˜†β˜†β˜†β˜†2018β†’ Residue 22
NM_012301.4(MAGI2):c.3526_3533dup (p.Glu1178fs)Pathogenic
Nephrotic syndrome 15
β˜†β˜†β˜†β˜†2018β†’ Residue 1178
View on ClinVar β†—
Related Genes
MAGI1Protein interaction99%RAPGEF6Protein interaction96%CTNNB1Protein interaction96%PTENProtein interaction95%MAGI3Protein interaction93%DLGAP1Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Ovary
49%
Heart
35%
Lung
13%
Liver
11%
Bone Marrow
7%
Gene Interaction Network
Click a node to explore
MAGI2MAGI1RAPGEF6CTNNB1PTENMAGI3DLGAP1
PROTEIN STRUCTURE
Preparing viewer…
PDB1UEP Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.37Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.27 [0.20–0.37]
RankingsWhere MAGI2 stands among ~20K protein-coding genes
  • #4,785of 20,598
    Most Researched100 Β· top quartile
  • #2,943of 5,498
    Most Pathogenic Variants9
  • #1,705of 17,882
    Most Constrained (LOEUF)0.37 Β· top 10%
Genes detectedMAGI2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.
PMID: 39169280
Cell Mol Biol Lett Β· 2024
1.00
2
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.
PMID: 38810140
Adv Sci (Weinh) Β· 2024
0.90
3
MAGI2/S-SCAM outside brain.
PMID: 25637633
J Biochem Β· 2015
0.80
4
MAGI2 Gene Region and Celiac Disease.
PMID: 31921880
Front Nutr Β· 2019
0.70
5
Roles of lncRNA MAGI2-AS3 in human cancers.
PMID: 34126355
Biomed Pharmacother Β· 2021
0.60