Table 1.

Major characteristics of Cl⁻-coupled cation cotransporters [10,11,12,13].

Gene	Human Chromosome Localization	Protein	Transported Ions	Alternative Spicing	Tissue Distribution, Cellular/Subcellular Expression	Link to Disease	Inhibitors, IC50 (μM)
SLC12A2	5q23.3	NKCC1	Na+, K+, Cl−	Isoforms A and B [14]	Ubiquitous: basolateral membrane of epithelial cells, non-epithelial cells	Schizophrenia [15]	Bumetanide, 0.05–0.60; Furosemide, 10–50; ARN23746 [16] Azosemide, 0.246–0.197
SLC12A1	15q21.1	NKCC2	Na+, K+, Cl−	Isoforms A, B and F [17]	Kidney-specific: apical membrane of the thick ascending limb	Bartter syndrome type I [18]	Bumetanide, 0.10–0.50; Furosemide, 15–60
SLC12A3	16q13	NCC	Na+, Cl−	NA	Kidney-specific: apical membrane of the distal convoluted tubule	Gitelman syndrome [19]	Hydrochlorothiazide, 70 [20]; Metolazone, 0.3 [21]
SLC12A4	16q22	KCC1	K+, Cl−	NA	Ubiquitous	NA	Bumetanide, 60 [22]; Furosemide, 40 [22]; DIOA, ~10
SLC12A5	20q13	KCC2	K+, Cl−	NA	Neurones	Epilepsy [23]	Bumetanide, 55; Furosemide, 10; VU 0463271, 0.061 [24]; DIOA, ~10
SLC12A6	15q14	KCC3	K+, Cl−	Isoforms A and B [25]	Ubiquitous	Agenesis of the Corpus Callosum with Peripheral Neuropathy (ACCPN) [26]	Bumetanide, 40; Furosemide, 25; DIOA,~10
SLC12A7	5p15	KCC4	K+, Cl−	NA	Ubiquitous	Renal tubular acidosis [27]	Bumetanide, 900; Furosemide, 900; DIOA, ~10
SLC12A8	3q21	CCC9	NA	Six isoforms [28]	Ubiquitous	Psoriasis [28]	NA
SLC12A9	7q22	CIP1	NA	NA	Ubiquitous	NA	NA

NA, information not available.