MAGI2: Membrane Associated Guanylate Kinase, WW and PDZ Domain Containing 2
A scaffold protein implicated in synaptic organization, renal function, and cancer
Gene Information Card
| Symbol | MAGI2 |
|---|---|
| Full Name | Membrane Associated Guanylate Kinase, WW and PDZ Domain Containing 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.11 |
| NCBI Gene ID | 9863 ncbi.nlm.nih.gov/gene/9863 |
| Ensembl ID | ENSG00000187391 |
| UniProt ID | Q86UL8 |
| OMIM ID | 606382 |
| HGNC ID | 18957 |
| Aliases | MAGI-2, ACVRIP1, ARIP1, AIP-1, AIP1, MAGI2 |
Description
MAGI2 encodes a scaffold protein belonging to the membrane-associated guanylate kinase (MAGUK) family. It contains multiple PDZ domains, a WW domain, and a guanylate kinase domain. MAGI2 is involved in synaptic organization, receptor clustering, and signal transduction. It interacts with proteins such as PTEN, beta-catenin, and NMDA receptors. Mutations in MAGI2 are associated with nephrotic syndrome type 15 and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephrotic syndrome type 15 (NPHS15) | Loss-of-function mutations disrupt glomerular podocyte structure and function | OMIM #617609; ClinVar |
| Schizophrenia | Genetic association studies suggest MAGI2 variants may contribute to synaptic dysfunction | PubMed; NCBI Gene |
| Cancer (breast, prostate, glioblastoma) | Altered MAGI2 expression affects PTEN stability and AKT signaling | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Kidney | 8.7 | Medium |
| Lung | 4.2 | Low |
| Liver | 1.5 | Low |
| Heart | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 6.8 | Embryonic kidney cells |
| SH-SY5Y | 9.5 | Neuroblastoma cells |
| MCF7 | 3.2 | Breast cancer cells |
| A549 | 2.9 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2458C>T (p.Arg820*) | Nonsense | Rare | Loss of function; associated with NPHS15 |
| c.1123G>A (p.Gly375Arg) | Missense | Rare | Likely pathogenic; disrupts PDZ domain |
| c.1891_1892del (p.Leu631fs) | Frameshift | Rare | Loss of function; reported in nephrotic syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in MAGI2 lead to truncated proteins lacking functional domains, resulting in loss of scaffold activity and contributing to nephrotic syndrome.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in MAGI2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type MAGI2 interactions, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • synaptic membrane adhesion | • protein domain specific binding |
| • PDZ domain binding | • guanylate kinase activity |
| • cell junction assembly | • signal transduction |
Pathways
• PTEN/AKT signaling pathway
• NMDA receptor signaling
• Wnt/beta-catenin signaling
• Cell junction organization
Protein Summary
MAGI2 is a multidomain scaffold protein that localizes to cell junctions and synapses. It contains 6 PDZ domains, a WW domain, and a guanylate kinase-like domain. MAGI2 stabilizes PTEN at the plasma membrane, modulates AKT signaling, and organizes receptor complexes at synapses. Its expression is highest in brain and kidney. Loss of MAGI2 function leads to podocyte damage and nephrotic syndrome, while altered expression is observed in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAGI2 Knockout HEK293 Cell Line | EDJ-KQ836 | Human | 9863 | Details Get a Quote |
| MAGI2 Knockout HeLa Cell Line | EDJ-KQ55267 | Human | 9863 | Details Get a Quote |
| MAGI2 Knockout A-549 Cell Line | EDJ-KQ63746 | Human | 9863 | Details Get a Quote |
| MAGI2 Knockout HCT 116 Cell Line | EDJ-KQ72206 | Human | 9863 | Details Get a Quote |
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