Defective SLC12A6 does not cotransport K+, Cl- from cytosol to extracellular region

Stable Identifier
R-HSA-5623806
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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K+/Cl- cotransport is implicated not only in regulatory volume decrease, but also in transepithelial salt absorption, renal K+ secretion, myocardial K+ loss during ischemia and regulation of neuronal Cl- concentration. Four genes (SLC12A4-7) encode the K+/Cl- cotransporters KCC1-4 respectively. Cotransport of K+ and Cl- is electroneutral with a 1:1 stoichiometry. These cotransporters function as homomultimers or heteromultimers with other K+/Cl- cotransporters. SLC12A6 encodes KCC3 which is highly expressed in heart, brain, spinal cord, kidney, muscle, pancreas and placenta. Defects in SLC12A6 are a cause of agenesis of the corpus callosum with peripheral neuropathy (ACCPN; MIM:218000), a autosomal recessive disease characterised by severe progressive sensorimotor neuropathy, mental retardation, dysmorphic features and variable degree of agenesis of the corpus callosum.

Mutations in SLC12A6 that can cause ACCPN include T813fs*813, F529fs*532, R1011*, R675* and R1134* (Howard et al. 2002, Salin-Cantegrel et al. 2011).

Literature References
PubMed ID Title Journal Year
21628467 Transit defect of potassium-chloride Co-transporter 3 is a major pathogenic mechanism in hereditary motor and sensory neuropathy with agenesis of the corpus callosum

Salin-Cantegrel, A, Rivière, JB, Shekarabi, M, Rasheed, S, Dacal, S, Laganière, J, Gaudet, R, Rochefort, D, Lesca, G, Gaspar, C, Dion, PA, Lapointe, JY, Rouleau, GA

J. Biol. Chem. 2011
12368912 The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum

Howard, HC, Mount, DB, Rochefort, D, Byun, N, Dupré, N, Lu, J, Fan, X, Song, L, Rivière, JB, Prévost, C, Horst, J, Simonati, A, Lemcke, B, Welch, R, England, R, Zhan, FQ, Mercado, A, Siesser, WB, George AL, Jr, McDonald, MP, Bouchard, JP, Mathieu, J, Delpire, E, Rouleau, GA

Nat Genet 2002
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
potassium:chloride symporter activity of SLC12A6 mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
peripheral neuropathy 0060053
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