Bartter disease type 4A

Summary

Bartter disease type 4A (MONDO:0011242) is a disease caused by BSND (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BSND (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bartter disease type 4A
Mondo ID	MONDO:0011242
OMIM	602522
DOID	DOID:0110145
SNOMED CT	717791000
UMLS	C1865270
MedGen	355430
GARD	0015348
Is cancer (heuristic)	no

Also known as: BARTS4A · Bartter disease type 4a · Bartter syndrome caused by mutation in BSND · BSND · BSND Bartter syndrome

Data availability: 84 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bartter syndrome › Bartter syndrome type 4 › Bartter disease type 4A

Related subtypes (1): Bartter disease type 4B

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

84 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 14 conflicting classifications of pathogenicity, 11 likely benign, 9 benign, 8 pathogenic/likely pathogenic, 7 pathogenic, 6 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179115	GRCh37/hg19 1p32.3(chr1:55464606-55482845)	BSND	Pathogenic	no assertion criteria provided
1323985	NM_057176.3(BSND):c.97G>C (p.Val33Leu)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3767333	NM_057176.3(BSND):c.556dup (p.Ala186fs)	BSND	Pathogenic	criteria provided, single submitter
4380	NM_057176.3(BSND):c.1A>T (p.Met1Leu)	BSND	Pathogenic	criteria provided, multiple submitters, no conflicts
4381	NM_057176.3(BSND):c.22C>T (p.Arg8Trp)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4382	NM_057176.3(BSND):c.157_177+20del	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4383	NM_057176.3(BSND):c.273-887_*576del	BSND	Pathogenic	no assertion criteria provided
4384	NM_057176.3(BSND):c.3G>A (p.Met1Ile)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4385	NM_057176.3(BSND):c.28G>A (p.Gly10Ser)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4386	NM_057176.3(BSND):c.23G>T (p.Arg8Leu)	BSND	Pathogenic	no assertion criteria provided
4387	NM_057176.3(BSND):c.139G>A (p.Gly47Arg)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4388	NM_057176.3(BSND):c.35T>C (p.Ile12Thr)	BSND	Pathogenic	criteria provided, multiple submitters, no conflicts
4389	NM_057176.3(BSND):c.10G>T (p.Glu4Ter)	BSND	Pathogenic	criteria provided, multiple submitters, no conflicts
620144	NM_057176.3(BSND):c.262G>T (p.Glu88Ter)	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
837720	NM_057176.3(BSND):c.272+1G>T	BSND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4526842	NM_057176.3(BSND):c.306G>A (p.Trp102Ter)	BSND	Likely pathogenic	criteria provided, single submitter
178291	NM_057176.3(BSND):c.457G>A (p.Asp153Asn)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2202510	NM_057176.3(BSND):c.23G>A (p.Arg8Gln)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225307	NM_057176.3(BSND):c.893G>A (p.Gly298Glu)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227188	NM_057176.3(BSND):c.102C>T (p.Tyr34=)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227191	NM_057176.3(BSND):c.309G>C (p.Glu103Asp)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290808	NM_057176.3(BSND):c.16A>G (p.Thr6Ala)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297677	NM_057176.3(BSND):c.216C>A (p.Ile72=)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297679	NM_057176.3(BSND):c.696G>A (p.Arg232=)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
46552	NM_057176.3(BSND):c.917T>C (p.Leu306Pro)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
590851	NM_057176.3(BSND):c.452del (p.Pro151fs)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
740286	NM_057176.3(BSND):c.547G>A (p.Gly183Ser)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875268	NM_057176.3(BSND):c.635A>G (p.Asn212Ser)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876316	NM_057176.3(BSND):c.261C>T (p.Ala87=)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876317	NM_057176.3(BSND):c.294T>C (p.Tyr98=)	BSND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
BSND	Definitive	Autosomal recessive	Bartter disease type 4A	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BSND	Orphanet:89938	Bartter syndrome type 4
BSND	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
BSND	HGNC:16512	ENSG00000162399	Q8WZ55	Barttin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BSND	Barttin	Regulatory subunit of anion-selective CLCNKA:BSND and CLCNKB:BSND heteromeric channels involved in basolateral chloride conductance along the nephron to achieve urine concentration and maintain systemic acid-base homeostasis, and in the st…

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)
BSND	Other/Unknown	no		Barttin

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
kidney epithelium	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BSND	22	tissue_specific	marker	kidney epithelium, adult mammalian kidney, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BSND	996

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BSND	Q8WZ55	53.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Stimuli-sensing channels	1	135.9×	0.016	BSND
Ion channel transport	1	96.0×	0.016	BSND
Transport of small molecules	1	25.1×	0.040	BSND

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
chloride transport	1	455.5×	0.004	BSND
sensory perception of sound	1	100.9×	0.010	BSND

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
BSND	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	BSND

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)
BSND	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.