Bartter disease type 1: genes and variants

Genes linked to Bartter disease type 1

• CLCNKB: Chloride channel protein ClC-Kb

  It supports chloride reabsorption in the thick ascending limb and distal nephron, helping establish salt balance and the kidney's concentrating gradient. Biallelic loss-of-function variants cause Bartter syndrome type 3 and can sometimes mimic Gitelman syndrome.

  16 disease-causing and 87 uncertain variants in CLCNKB are linked to Bartter disease type 1.

• SLC12A1: Solute carrier family 12 member 1

  It reabsorbs sodium, potassium, and chloride in the thick ascending limb of the kidney, helping generate the medullary concentration gradient and maintain salt balance. Biallelic loss-of-function variants cause Bartter syndrome type 1 with renal salt wasting.

  14 disease-causing and 158 uncertain variants in SLC12A1 are linked to Bartter disease type 1.

Weakly linked (only a few uncertain records): MAGED2.

Where Bartter disease type 1 variants cluster

• CLCNKB Transmembrane (positions 421–440): 6 of 16 disease-causing changes, 12.9× more than its size predicts.
• SLC12A1 Extracellular (positions 439–550): 6 of 14 disease-causing changes, 4.2× more than its size predicts.
• SLC12A1 Transmembrane (positions 551–571): 3 of 14 disease-causing changes, 11.2× more than its size predicts.

Known disease-causing variants in Bartter disease type 1

Which prediction tools work for Bartter disease type 1

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 98 out of 100
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 94 out of 100
• phyloP: 89 out of 100

Diseases related to Bartter disease type 1

• Bartter syndrome, also linked to CLCNKB and SLC12A1
• Nephrotic syndrome, also linked to SLC12A1
• Kidney disorder, also linked to SLC12A1

Frequently asked questions

Which genes are linked to Bartter disease type 1?

In CATVariant, Bartter disease type 1 is linked to 2 analyzed proteins: CLCNKB (Chloride channel protein ClC-Kb) and SLC12A1 (Solute carrier family 12 member 1).

How many genetic variants are linked to Bartter disease type 1?

321 variants: 30 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 248 are of uncertain significance or have conflicting reports.

Which uncertain variants in Bartter disease type 1 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Bartter disease type 1?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 24 disease-causing and 43 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

Download every variant as CSV · Browse all diseases · Methods · About the Center