Bartter disease type 2

Summary

Bartter disease type 2 (MONDO:0009424) is a disease caused by KCNJ1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: KCNJ1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 158

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bartter disease type 2
Mondo ID	MONDO:0009424
MeSH	C537651
OMIM	241200
Orphanet	620220
DOID	DOID:0110143
SNOMED CT	700109009
UMLS	C1855849
MedGen	343428
GARD	0022483
Is cancer (heuristic)	no

Also known as: BARTS2 · Bartter disease type 2 · Bartter syndrome antenatal type 2 · Bartter syndrome caused by mutation in KCNJ1 · Bartter syndrome type 2 · Bartter syndrome, type 2 · hyperprostaglandin E syndrome 2 · hypokalemic alkalosis with hypercalciuria antenatal 2 · KCNJ1 Bartter syndrome

Data availability: 158 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 2

Related subtypes (5): Bartter disease type 5, 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

158 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 30 likely pathogenic, 18 conflicting classifications of pathogenicity, 12 pathogenic/likely pathogenic, 11 pathogenic, 6 likely benign, 3 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1482322	NM_153766.3(KCNJ1):c.875G>A (p.Arg292Gln)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683231	NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803985	NM_153766.3(KCNJ1):c.251C>T (p.Ala84Val)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627549	NM_153766.3(KCNJ1):c.514A>C (p.Thr172Pro)	KCNJ1	Pathogenic	criteria provided, single submitter
2825619	NM_153766.3(KCNJ1):c.504dup (p.Arg169fs)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2852764	NM_153766.3(KCNJ1):c.416_417del (p.Phe139fs)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
303573	NM_153766.3(KCNJ1):c.577C>T (p.Arg193Ter)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3599153	NM_153766.3(KCNJ1):c.983del (p.Thr328fs)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373897	NM_153766.3(KCNJ1):c.262A>T (p.Lys88Ter)	KCNJ1	Pathogenic	no assertion criteria provided
523794	NM_153766.3(KCNJ1):c.955C>T (p.Arg319Ter)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
586075	NM_153766.3(KCNJ1):c.1001dup (p.His335fs)	KCNJ1	Pathogenic	criteria provided, multiple submitters, no conflicts
586076	NM_153766.3(KCNJ1):c.867C>A (p.Cys289Ter)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631655	NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met)	KCNJ1	Pathogenic	criteria provided, multiple submitters, no conflicts
694393	NM_153766.3(KCNJ1):c.504del (p.Lys168fs)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
872042	NM_153766.3(KCNJ1):c.939_942del (p.Glu315fs)	KCNJ1	Pathogenic	criteria provided, multiple submitters, no conflicts
9153	NM_153766.3(KCNJ1):c.180C>G (p.Tyr60Ter)	KCNJ1	Pathogenic	no assertion criteria provided
9154	NM_153766.3(KCNJ1):c.42dup (p.Gly15fs)	KCNJ1	Pathogenic	no assertion criteria provided
9155	NM_153766.3(KCNJ1):c.600C>G (p.Ser200Arg)	KCNJ1	Pathogenic	criteria provided, single submitter
9156	KCNJ1, TRP58TER	KCNJ1	Pathogenic	no assertion criteria provided
9161	NM_153766.3(KCNJ1):c.265G>C (p.Asp89His)	KCNJ1	Pathogenic	no assertion criteria provided
9162	NM_153766.3(KCNJ1):c.315T>A (p.Asn105Lys)	KCNJ1	Pathogenic	no assertion criteria provided
978165	NM_153766.3(KCNJ1):c.89G>A (p.Cys30Tyr)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
981532	NM_153766.3(KCNJ1):c.272C>T (p.Pro91Leu)	KCNJ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333621	NM_153766.3(KCNJ1):c.550C>T (p.Arg184Trp)	KCNJ1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1879219	NM_153766.3(KCNJ1):c.76A>G (p.Lys26Glu)	KCNJ1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664766	NM_153766.3(KCNJ1):c.118C>T (p.Gln40Ter)	KCNJ1	Likely pathogenic	criteria provided, single submitter
2735787	NM_153766.3(KCNJ1):c.240G>T (p.Trp80Cys)	KCNJ1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064889	NM_153766.3(KCNJ1):c.240G>A (p.Trp80Ter)	KCNJ1	Likely pathogenic	criteria provided, single submitter
3068007	NM_153766.3(KCNJ1):c.240_242delinsCTT (p.Trp80_Tyr81delinsCysPhe)	KCNJ1	Likely pathogenic	criteria provided, single submitter
3068341	NM_153766.3(KCNJ1):c.899_900del (p.Val300fs)	KCNJ1	Likely pathogenic	criteria provided, single submitter

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
KCNJ1	Definitive	Autosomal recessive	Bartter disease type 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNJ1	Orphanet:620220	Bartter syndrome type 2

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
KCNJ1	HGNC:6255	ENSG00000151704	P48048	ATP-sensitive inward rectifier potassium channel 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ1	ATP-sensitive inward rectifier potassium channel 1	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNJ1	Ion channel	yes		K_chnl_inward-rec_Kir1.1, K_chnl_inward-rec_Kir_cyto, Ig_E-set

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
adult mammalian kidney	1
nephron tubule	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ1	131	tissue_specific	marker	renal medulla, adult mammalian kidney, nephron tubule

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNJ1	1,173

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNJ1	P48048	84.79

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
Potassium transport channels	1	3806.7×	0.001	KCNJ1
Inwardly rectifying K+ channels	1	713.8×	0.003	KCNJ1
Potassium Channels	1	134.3×	0.010	KCNJ1
Neuronal System	1	44.3×	0.023	KCNJ1

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
circulatory system development	1	1404.3×	0.004	KCNJ1
renal sodium ion absorption	1	991.3×	0.004	KCNJ1
regulation of monoatomic ion transmembrane transport	1	732.7×	0.004	KCNJ1
tissue homeostasis	1	561.7×	0.004	KCNJ1
potassium ion import across plasma membrane	1	366.4×	0.005	KCNJ1
post-embryonic development	1	205.5×	0.007	KCNJ1
monoatomic ion transport	1	156.0×	0.008	KCNJ1
kidney development	1	140.4×	0.008	KCNJ1
gene expression	1	79.9×	0.013	KCNJ1

Therapeutics

Drug target analysis

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

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
KCNJ1	1	1

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MK-7145	1	KCNJ1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNJ1	61	Binding:59, Functional:1, ADMET:1

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MK-7145	1	KCNJ1

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	1	KCNJ1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.