MAGED2

Chr XXLR

MAGE family member D2

Also known as: 11B6, BARTS5, BCG-1, BCG1, HCA10, MAGE-D2

NCBI Gene: 10916ENSG00000102316UniProt: Q9UNF1OMIM: 300470

The MAGED2 protein regulates the expression, localization, and function of sodium chloride cotransporters SLC12A1 and SLC12A3, which are essential for salt reabsorption in the distal renal tubule. Mutations cause transient antenatal Bartter syndrome, an X-linked recessive disorder affecting renal salt handling that typically presents during fetal development. This gene is highly constrained against loss-of-function variants (pLI 0.995), indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismXLRLOEUF 0.231 OMIM phenotype
Clinical Summary— MAGED2
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Gene-Disease Validity (ClinGen)
Bartter disease type 5 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 83 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.995
Z-score 3.97
OE 0.05 (0.02–0.23)
Highly constrained

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

Missense Constraint
2.34Z-score
OE missense 0.56 (0.49–0.65)
128 obs / 227.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.02–0.23)
0≤0.351.4
Missense OE0.56 (0.49–0.65)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 1 / 20.3Missense obs/exp: 128 / 227.2Syn Z: 0.54
DN
0.3097th %ile
GOF
0.3193th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 18% of P/LP variants are LoF · LOEUF 0.23

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic8
VUS83
Likely Benign32
Benign41
Conflicting4
49
Pathogenic
8
Likely Pathogenic
83
VUS
32
Likely Benign
41
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
43
0
49
Likely Pathogenic
4
1
3
0
8
VUS
5
63
12
3
83
Likely Benign
0
6
7
19
32
Benign
0
5
18
18
41
Conflicting
—4
Total15758340217

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

View in ClinVar →

Protein Context — Lollipop Plot

MAGED2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients