Defective SLC12A1 does not cotransport Na+, K+, 2Cl- from extracellular region to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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The solute carrier family 12 member 1 (SLC12A1, NKCC2) is a kidney-specific, membrane-bound protein that cotransports two Cl- ions electroneutrally into cells with a Na+ ion and a K+ ion and plays a vital role in the regulation of ionic balance and cell volume. Defects in SLC12A1 can cause Bartter’s syndrome (BS1; MIM:601678), an autosomal-recessive disease salt-wasting disorder characterised by renal tubular hypokalaemia, metabolic alkalosis and hypercalciuria. Clinical features present in infancy and include muscle weakness, anorexia, polydipsia, polyuria, failure to thrive and mental and growth retardation.

Loss-of-function defects in SLC12A1 that cause BS1 include D648N, V272F (Simon et al. 1996), R302Q, G319R (Vargas-Poussou et al. 1998), W625X (Kurtz et al. 1997) and Y998* (Vargas-Poussou et al. 1998).
Literature References
PubMed ID Title Journal Year
8640224 Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2

Lifton, RP, Hamdan, JM, DiPietro, A, Simon, DB, Karet, FE, Sanjad, SA

Nat Genet 1996
9585600 Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome

Lemmink, HH, Vollmer, M, Deschênes, G, Seyberth, HW, Brandis, M, van den Heuvel, LP, Kelly, L, Konrad, M, Antignac, C, Hildebrandt, F, Feldmann, D, Karolyi, L, Tebourbi, L, Knoers, NV, Hebert, SC, Guay-Woodford, LM, Vargas-Poussou, R

Am. J. Hum. Genet. 1998
9355073 A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect

Vargas, R, Vollmer, M, Madrigal, G, Feldmann, D, Seyberth, HW, Karolyi, L, Kurtz, CL, Knoers, NV, Guay-Woodford, LM, Koch, MC

J. Am. Soc. Nephrol. 1997
Catalyst Activity

sodium:potassium:chloride symporter activity of SLC12A1 mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of SLC12A1 mutants [plasma membrane]

Name Identifier Synonyms
Bartter disease DOID:445 Aldosteronism with hyperplasia of the adrenal cortex, Bartter's syndrome, Bartter's syndrome, Bartter's syndrome, Bartter's syndrome
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