MAGED2

Chr X

MAGE family member D2

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

NCBI Gene: 10916 ENSG00000102316 UniProt: Q9UNF1

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.

ResearchSummary from RefSeq, UniProt

This gene is a member of the MAGED gene family. The MAGED genes are clustered on chromosome Xp11. This gene is located in Xp11.2, a hot spot for X-linked intellectual disability (XLID). Mutations in this gene cause a form of transient antenatal Bartter's syndrome. This gene may also be involved in several types of cancer, including breast cancer and melanoma. The protein encoded by this gene is progressively recruited from the cytoplasm to the nucleoplasm during the interphase and after nucleolar stress and is thus thought to play a role in cell cycle regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.23

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

11 unique Pathogenic / Likely Pathogenic· 78 VUS of 249 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.05 (0.02–0.23)

0≤0.351.4

Missense OE?0.56 (0.49–0.65)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 1 / 20.3Missense obs/exp: 128 / 227.2Syn Z: 0.54

This gene — mechanism propensity

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 · 91% 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

249 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic5

VUS78

Likely Benign32

Benign41

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	0	0	0	6
Likely Pathogenic	4	1	0	0	5
VUS	5	62	8	3	78
Likely Benign	0	6	7	19	32
Benign	0	5	18	18	41
Conflicting	—				4
Total	15	74	33	40	166

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

View in ClinVar →

46 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap MAGED2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →