MAGED2

Chr XXLR

MAGE family member D2

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

NCBI Gene: 10916 ENSG00000102316 UniProt: Q9UNF1 OMIM: 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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bartter syndrome, type 5, antenatal, transientMIM #300971

XLR

UniProtBartter syndrome 5, antenatal, transient

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Bartter disease type 5 · XL · ClinGen 2022

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

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

Background carrier burden — how many people carry a rare variant somewhere in MAGED2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

367 rare PASS variants

Rare truncating (LoF)

1 in 12,000

13 rare PASS variants

Rare synonymous (reference)

1 in 260

155 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAGED2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 220	1 in 11,000
South Asian	~36k	1 in 170	≈ 1 in 18,000
Remaining (unassigned)	~31k	1 in 230	≈ 1 in 10,000
European (Finnish)	~27k	1 in 1,200	≈ 1 in 27,000
Admixed American	~23k	1 in 150	≈ 1 in 5,200
African / African American	~21k	1 in 170	≈ 1 in 17,000
East Asian	~20k	1 in 180	none seen
Ashkenazi Jewish	~13k	1 in 2,100	none seen
Middle Eastern	~2,758	1 in 270	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓