MAGI2

Chr 7AR

membrane associated guanylate kinase, WW and PDZ domain containing 2

Also known as: ACVRIP1, AIP-1, AIP1, ARIP1, MAGI-2, NPHS15, SSCAM

NCBI Gene: 9863ENSG00000187391UniProt: Q86UL8

The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 15MIM #617609
AR
82
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MAGI2
🧬
Gene-Disease Validity (ClinGen)
epilepsy · ADRefuted

Refuted — evidence has disproved this relationship

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 60 VUS of 82 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 0.999
Z-score 6.18
OE 0.15 (0.09–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.81Z-score
OE missense 0.82 (0.76–0.87)
632 obs / 774.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.09–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.76–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 9 / 61.2Missense obs/exp: 632 / 774.1Syn Z: 0.25

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1
VUS60
Likely Benign21
1
Likely Pathogenic
60
VUS
21
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
1
0
0
0
1
VUS
1
56
3
0
60
Likely Benign
0
1
9
11
21
Benign
0
0
0
0
0
Total257121182

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAGI2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MAGI2-related early onset epileptic encephalopathy

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Nephrotic syndrome, type 15

MIM #617609

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.
Jin Q et al.·Cell Mol Biol Lett
2024
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.
Wang G et al.·Adv Sci (Weinh)
2024Functional
Role of MAGI2-AS3 in malignant and non-malignant disorders.
Taheri M et al.·Pathol Res Pract
2023Review
Roles of lncRNA MAGI2-AS3 in human cancers.
Kai-Xin L et al.·Biomed Pharmacother
2021Review
Novel insights for lncRNA MAGI2-AS3 in solid tumors.
Xue C et al.·Biomed Pharmacother
2021Review
lncRNA MAGI2-AS3 suppresses castration-resistant prostate cancer proliferation and migration via the miR-106a-5p/RAB31 axis.
Yang G et al.·Genomics
2023
Expression and clinical significance of SYNE1 and MAGI2 gene promoter methylation in gastric cancer.
Qu Y et al.·Medicine (Baltimore)
2021
LncRNA MAGI2-AS3 Inhibits Prostate Cancer Progression by Targeting the miR-142-3p.
Hu R et al.·Horm Metab Res
2022
LncRNA MAGI2-As3 Suppresses the Proliferation and Invasion of Cervical Cancer by Sponging MiR-15b.
Chai Y et al.·J Healthc Eng
2022
MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights.
Kortam MA et al.·ACS Chem Neurosci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The neuroprotective effect of LncRNA MAGI2-AS3 against cerebral ischemia-reperfusion injury via targeting miR-218-5p.
Li B et al.·J Stroke Cerebrovasc Dis
2025
Hypermethylated Long Non-Coding RNA Genes KCNK15-AS1, MAGI2-AS3, and SSTR5-AS1 in Ovarian Cancer and Their Diagnostic Potential.
Lukina SS et al.·Bull Exp Biol Med
2025
The lncRNA MAGI2-AS3 in peripheral blood mononuclear cells: a valuable biomarker for diagnosis and prognosis prediction of breast cancer.
Du S et al.·PeerJ
2025🔓 Open Access
The differential expression of MAGI2 in glomerulopathies and its application as a molecular discriminator of podocytopathies.
Siegerist F et al.·J Transl Med
2025🔓 Open Access
LncRNA MAGI2-AS3 promotes the progression of atherosclerosis by sponging miR-525-5p.
Zhu L et al.·J Cardiothorac Surg
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools