Bartter disease type 5

Summary

Bartter disease type 5 (MONDO:0010503) is a disease caused by MAGED2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MAGED2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Bartter disease type 5
Mondo ID	MONDO:0010503
OMIM	300971
Orphanet	570371
DOID	DOID:0110147
UMLS	C4310820
MedGen	934787
GARD	0022308
Is cancer (heuristic)	no

Also known as: BARTS5 · Bartter syndrome caused by mutation in MAGED2 · Bartter syndrome, type 5, antenatal, transient · Bartter syndrome, type 5, antenatal, transient, X-linked recessive · MAGED2 Bartter syndrome

Data availability: 22 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bartter syndrome › Bartter disease type 5

Related subtypes (5): Bartter disease type 2, Bartter disease type 3, Bartter syndrome with hypocalcemia, Bartter syndrome type 4, Bartter disease type 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

7 pathogenic, 6 uncertain significance, 4 benign, 4 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
226031	NM_177433.3(MAGED2):c.1038C>G (p.Tyr346Ter)	MAGED2	Pathogenic	no assertion criteria provided
226032	NM_177433.3(MAGED2):c.991-2A>G	MAGED2	Pathogenic	no assertion criteria provided
226033	NM_177433.3(MAGED2):c.386_387del (p.Val129fs)	MAGED2	Pathogenic	no assertion criteria provided
226035	NM_177433.3(MAGED2):c.397A>T (p.Lys133Ter)	MAGED2	Pathogenic	no assertion criteria provided
2575215	NM_177433.3(MAGED2):c.262C>T (p.Gln88Ter)	MAGED2	Pathogenic	criteria provided, single submitter
2687474	NM_177433.3(MAGED2):c.1271+4_1271+7del	MAGED2	Pathogenic	no assertion criteria provided
3893182	NM_177433.3(MAGED2):c.1329G>A (p.Trp443Ter)	MAGED2	Pathogenic	criteria provided, single submitter
1805201	NM_177433.3(MAGED2):c.1386+1G>A	MAGED2	Likely pathogenic	criteria provided, single submitter
226034	NM_177433.3(MAGED2):c.1336C>T (p.Arg446Cys)	MAGED2	Likely pathogenic	criteria provided, single submitter
4056395	NM_177433.3(MAGED2):c.1452GGCTGCAGCTGA[1] (p.486AAEA[1])	MAGED2	Likely pathogenic	criteria provided, single submitter
4531339	NM_177433.3(MAGED2):c.1347T>G (p.Tyr449Ter)	MAGED2	Likely pathogenic	criteria provided, single submitter
2096189	NM_177433.3(MAGED2):c.457C>T (p.Pro153Ser)	MAGED2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433602	NM_177433.3(MAGED2):c.1425C>G (p.Tyr475Ter)	MAGED2	Uncertain significance	criteria provided, single submitter
2582619	NM_177433.3(MAGED2):c.990G>A (p.Lys330=)	MAGED2	Uncertain significance	criteria provided, single submitter
3061845	NM_177433.3(MAGED2):c.968G>A (p.Arg323Gln)	MAGED2	Uncertain significance	criteria provided, single submitter
3382890	NM_177433.3(MAGED2):c.1337G>A (p.Arg446His)	MAGED2	Uncertain significance	criteria provided, single submitter
3572901	NM_177433.3(MAGED2):c.1208+96G>A	MAGED2	Uncertain significance	criteria provided, single submitter
1244776	NM_177433.3(MAGED2):c.252A>G (p.Ser84=)	MAGED2	Benign	criteria provided, multiple submitters, no conflicts
1258035	NM_177433.3(MAGED2):c.396A>G (p.Thr132=)	MAGED2	Benign	criteria provided, multiple submitters, no conflicts
1278258	NM_177433.3(MAGED2):c.981C>T (p.Ser327=)	MAGED2	Benign	criteria provided, multiple submitters, no conflicts
1279142	NM_177433.3(MAGED2):c.624C>T (p.Ala208=)	MAGED2	Benign	criteria provided, multiple submitters, no conflicts
786394	NM_177433.3(MAGED2):c.816A>G (p.Pro272=)	MAGED2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MAGED2	Definitive	X-linked	Bartter disease type 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAGED2	Orphanet:570371	Bartter syndrome type 5

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAGED2	HGNC:16353	ENSG00000102316	Q9UNF1	Melanoma-associated antigen D2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAGED2	Melanoma-associated antigen D2	Regulates the expression, localization to the plasma membrane and function of the sodium chloride cotransporters SLC12A1 and SLC12A3, two key components of salt reabsorption in the distal renal tubule.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAGED2	Other/Unknown	no		MHD_dom, MAGE, MAGE_WH1

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAGED2	291	ubiquitous	marker	left ovary, adenohypophysis, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAGED2	1,351

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAGED2	Q9UNF1	59.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.015	MAGED2
Platelet activation, signaling and aggregation	1	105.7×	0.015	MAGED2
Platelet degranulation	1	87.8×	0.015	MAGED2
Hemostasis	1	36.0×	0.028	MAGED2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
renal sodium ion absorption	1	991.3×	0.003	MAGED2
female pregnancy	1	210.7×	0.007	MAGED2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	MAGED2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAGED2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MAGED2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MAGED2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.