Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Sodium-potassium-chloride transporter 2

The gene SLC12A1 encoding a sodium-potassium-chloride cotransporter (NKCC2) is expressed in the thick ascending limb of the loop of Henle. Inactivating mutations are known to cause autosomal recessive antenatal Bartter syndrome type 1.

Epidemiology

Although exact data are not available, mutation in this gene are thought to occur 1 in 50,000-100,000 newborn.

Gene Structure

The SLC12A1 gene belongs to a superfamily of electroneutral cotransporters, which include another basolateral sodium-potassium-chloride cotransporter, a sodium-chloride cotransporter, and four potassium-chloride cotransporters. These genes are highly homologeous.

The gene is translated into six different isoforms. These isoforms can be formed by anycombination of tree differens exon four cassettes and two alternative C-termini. These isoforms behave distinctively, which allows to fine tune the transport capacity in accordance to the increasingly dilute urine.

Expression

The sodium-potassium-chloride cotransporter (NKCC2) is an apical membrane protein of the thick ascending limb of Henle. The six isoforms exhibit different kinetic behaviour. Accompanying the progressive dilution of the urine, these isoforms diplay a distinct axial distribution.

Phenotype

Mutations of the SLC12A1 gene ensuing inactivation of the sodium-potassium-chloride cotransporter increase water and salt excretion which becomes noticable before birth, by polyhydramnion. The disease is called antenatal Bartter-syndrome 1.

Genetests:

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 10 days
Specimen type genomic DNA

Related Diseases:

Antenatal Bartter syndrome type 1
SLC12A1

References:

1.

Starremans PG et al. (2003) Dimeric architecture of the human bumetanide-sensitive Na-K-Cl Co-transporter.

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2.

NCBI article

NCBI 6557 [^]
3.

OMIM.ORG article

Omim 600839 [^]
4.

Orphanet article

Orphanet ID 118737 [^]
5.

Wikipedia article

Wikipedia EN (Na-K-Cl_cotransporter) [^]
Update: April 29, 2019