Bartter syndrome: genes and variants

Genes linked to Bartter syndrome

• 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.

  3 disease-causing and 0 uncertain variants in CLCNKB are linked to Bartter syndrome.

• 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.

  2 disease-causing and 3 uncertain variants in SLC12A1 are linked to Bartter syndrome.

• MAGED2: Melanoma-associated antigen D2

  It regulates membrane-protein trafficking in renal tubule cells and helps maintain expression of salt-transport proteins during fetal kidney development. Hemizygous loss-of-function variants cause transient antenatal Bartter syndrome, which often improves substantially after birth.

  0 disease-causing and 0 uncertain variants in MAGED2 are linked to Bartter syndrome.

• SLC12A3: Solute carrier family 12 member 3

  It reabsorbs sodium and chloride in the distal convoluted tubule and is a major determinant of renal salt and magnesium handling. Biallelic loss-of-function variants cause Gitelman syndrome with hypokalemic metabolic alkalosis, hypomagnesemia, and low urinary calcium.

  0 disease-causing and 3 uncertain variants in SLC12A3 are linked to Bartter syndrome.

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

Known disease-causing variants in Bartter syndrome

Same protein, different disease

• Bartter disease type 1 is also caused by CLCNKB variants; they fall mostly in different places as the Bartter syndrome variants (16 disease-causing).
• Bartter disease type 1 is also caused by SLC12A1 variants; they fall mostly in different places as the Bartter syndrome variants (14 disease-causing).

Diseases related to Bartter syndrome

• Nephrotic syndrome, also linked to SLC12A1 and SLC12A3
• Bartter disease type 1, also linked to CLCNKB and SLC12A1
• Familial hypokalemia-hypomagnesemia, also linked to SLC12A3
• Renal tubulopathies, also linked to SLC12A3
• Myocardial infarction, also linked to SLC12A3
• Kidney disorder, also linked to SLC12A1
• Chronic kidney disease, also linked to SLC12A3
• Renal tubular acidosis, also linked to SLC12A3

Frequently asked questions

Which genes are linked to Bartter syndrome?

In CATVariant, Bartter syndrome is linked to 4 analyzed proteins: CLCNKB (Chloride channel protein ClC-Kb), SLC12A1 (Solute carrier family 12 member 1), MAGED2 (Melanoma-associated antigen D2) and SLC12A3 (Solute carrier family 12 member 3).

How many genetic variants are linked to Bartter syndrome?

72 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 7 are of uncertain significance or have conflicting reports.

Which uncertain variants in Bartter syndrome look disease-causing?

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

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.

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