Bartter disease type 1

Summary

Bartter disease type 1 (MONDO:0100344) is a disease caused by SLC12A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC12A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 340

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bartter disease type 1
Mondo ID	MONDO:0100344
MeSH	C537652
OMIM	601678
Orphanet	620217
DOID	DOID:0110142
SNOMED CT	700107006
UMLS	C1866495
MedGen	355727
GARD	0022482
Is cancer (heuristic)	no

Also known as: antenatal Bartter syndrome type 1 · BARTS1 · Bartter disease type 1 · Bartter syndrome antenatal type 1 · Bartter syndrome caused by mutation in SLC12A1 · Bartter syndrome type 1 · Bartter syndrome, furosemide type · Bartter syndrome, furosemide-amiloride type · Bartter syndrome, type 1 · hyperprostaglandin E syndrome · hyperprostaglandin E syndrome 1 · hypokalemic alkalosis with hypercalciuria antenatal 1 · SLC12A1 Bartter syndrome

Data availability: 340 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bartter syndrome › Bartter disease type 1

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

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

340 retrieved; paginated sample, class counts are floors:

196 uncertain significance, 42 conflicting classifications of pathogenicity, 32 likely pathogenic, 18 pathogenic, 17 pathogenic/likely pathogenic, 15 benign/likely benign, 12 benign, 8 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2571667	NM_000338.3(SLC12A1):c.[1154_1157dup];[2770C>T]		Pathogenic	criteria provided, single submitter
424798	NM_000338.2(SLC12A1):c.[1522G>A];[735C>G]		Pathogenic	criteria provided, single submitter
378051	NM_000338.3(SLC12A1):c.1833del (p.Phe611fs)	LOC126862123	Pathogenic	criteria provided, multiple submitters, no conflicts
1067800	NM_000338.3(SLC12A1):c.3164+1G>A	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070803	NM_000338.3(SLC12A1):c.2716C>T (p.Gln906Ter)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180662	NM_000338.3(SLC12A1):c.2584A>T (p.Lys862Ter)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299701	NM_000338.3(SLC12A1):c.2805dup (p.Trp936fs)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320258	NM_000338.3(SLC12A1):c.382C>T (p.Arg128Ter)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1323598	NM_000338.3(SLC12A1):c.2042+2T>A	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342020	NM_000338.3(SLC12A1):c.223C>T (p.Gln75Ter)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1343249	NM_000338.3(SLC12A1):c.1316G>A (p.Arg439Gln)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1407972	NM_000338.3(SLC12A1):c.1103A>G (p.Glu368Gly)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1407973	NM_000338.3(SLC12A1):c.1432G>A (p.Gly478Arg)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2190892	NM_000338.3(SLC12A1):c.1315C>T (p.Arg439Ter)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
242488	NM_000338.3(SLC12A1):c.1522G>A (p.Ala508Thr)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2428826	NM_000338.3(SLC12A1):c.2281C>T (p.Arg761Ter)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2500697	NM_000338.3(SLC12A1):c.1966C>T (p.Gln656Ter)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
265999	NM_000338.3(SLC12A1):c.1163del (p.Phe388fs)	SLC12A1	Pathogenic	criteria provided, single submitter
2731628	NM_000338.3(SLC12A1):c.450_451del (p.Asp150fs)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2736214	NM_000338.3(SLC12A1):c.904del (p.Arg302fs)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2736215	NM_000338.3(SLC12A1):c.1411C>T (p.Arg471Ter)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2888918	NM_000338.3(SLC12A1):c.2047C>T (p.Gln683Ter)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2963069	NM_000338.3(SLC12A1):c.847_848del (p.Val283fs)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3012081	NM_000338.3(SLC12A1):c.1087+2T>C	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
378047	NM_000338.3(SLC12A1):c.1137del (p.Phe380fs)	SLC12A1	Pathogenic	no assertion criteria provided
378049	NM_000338.3(SLC12A1):c.2787dup (p.Thr931fs)	SLC12A1	Pathogenic	no assertion criteria provided
378050	NM_000338.3(SLC12A1):c.2498_2499del (p.Arg833fs)	SLC12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
548675	NM_000338.3(SLC12A1):c.769G>A (p.Gly257Ser)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
805466	NM_000338.3(SLC12A1):c.2869dup (p.Ile957fs)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
847437	NM_000338.3(SLC12A1):c.1687dup (p.Glu563fs)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
SLC12A1	Definitive	Autosomal recessive	antenatal Bartter syndrome	4

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
SLC12A1	HGNC:10910	ENSG00000074803	Q13621	Solute carrier family 12 member 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC12A1	Solute carrier family 12 member 1	Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.

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)
SLC12A1	Other/Unknown	no		SLC12A1/SLC12A2, Slc12a1, AA-permease/SLC12A_dom

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
metanephros cortex	1
nephron tubule	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC12A1	185	tissue_specific	marker	renal medulla, nephron tubule, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC12A1	1,448

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC12A1	Q13621	78.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1	11420.0×	7e-04	SLC12A1
Cation-coupled Chloride cotransporters	1	1631.4×	0.002	SLC12A1
SLC transporter disorders	1	203.9×	0.012	SLC12A1
Disorders of transmembrane transporters	1	139.3×	0.012	SLC12A1
R-HSA-425393	1	129.8×	0.012	SLC12A1
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC12A1
Transport of small molecules	1	25.1×	0.045	SLC12A1
Disease	1	13.1×	0.076	SLC12A1

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
transepithelial ammonium transport	1	3370.4×	0.002	SLC12A1
ammonium homeostasis	1	2407.4×	0.002	SLC12A1
chloride ion homeostasis	1	1532.0×	0.002	SLC12A1
sodium ion homeostasis	1	936.2×	0.003	SLC12A1
potassium ion homeostasis	1	766.0×	0.003	SLC12A1
cell volume homeostasis	1	601.9×	0.003	SLC12A1
potassium ion import across plasma membrane	1	366.4×	0.004	SLC12A1
chloride transmembrane transport	1	237.3×	0.005	SLC12A1
monoatomic ion transmembrane transport	1	208.1×	0.005	SLC12A1
sodium ion transmembrane transport	1	203.0×	0.005	SLC12A1
monoatomic ion transport	1	156.0×	0.006	SLC12A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC12A1	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	SLC12A1

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)
SLC12A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.