The gene encodes the thiazide-sensitive sodium-chloride co-trasnporter. Mutations cause Gitelman syndrome.
Only few families are known so far. About 50 mutations are identified.
The gene is about 49 kb in size. It was recovered as the receptor for thiazide diuretics (NCCT, TSC). The current acronym is SLC12A3 because it belongs to solute cotransporters. It is located on chromosome 16 at position 16q13. The gene consists of 26 exons.
The clinical picture of loss-of-function mutations in this gene is known as Gitelman syndrome. It is an autosomal recessive disorder disorder characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. Clinical symptoms are similar to overdosage of thiazides. ECG changes consistend with long QT syndrome also have been reported.
The translation product is a protein of 112 kD (1,021 amino acids). This protein consists of 12 membrane spanning domains and 2 intracellular hydrophilic amino and carboxyl termini. The gene is predominantly expressed in kidneys, in the distal convoluted tubule. Its main task is sodium reabsorbtion. Thiazides block this cotransporter.
Predominant indications for molecular diagnostic are family counseling and improvement of diagnostic precision.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 20 days | |
Specimen type | genomic DNA |
Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
Turnaround | 20 days | |
Specimen type | genomic DNA |
1. |
Cruz DN et al. (2001) Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life. |
2. |
Roser M et al. (2009) Gitelman syndrome. |
3. |
Bettinelli A et al. (1995) Genetic heterogeneity in tubular hypomagnesemia-hypokalemia with hypocalcuria (Gitelman's syndrome). |
4. |
Simon DB et al. (1996) Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. |
5. |
NCBI article NCBI 6559 |
6. |
OMIM.ORG article Omim 600968 |
7. |
Orphanet article Orphanet ID 118740 |
8. |
Wikipedia article Wikipedia EN (Sodium-chloride_symporter) |