The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SLC12A4  -  solute carrier family 12...

Homo sapiens

Synonyms: Electroneutral potassium-chloride cotransporter 1, Erythroid K-Cl cotransporter 1, KCC1, Solute carrier family 12 member 4, hKCC1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on SLC12A4

  • Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element [1].
  • K-Cl cotransport is elevated in sickle erythrocytes, and the KCC1 gene has been proposed as a modifier gene in sickle cell disease [1].
  • Functional assays of KCl cotransport activation by osmotic swelling, staurosporine, and N-ethylmaleimide indicate that removal of the N-terminal 117 amino acids from KCC1 produces a dominant-negative loss-of-function phenotype for KCl cotransport in human cervical cancer cells [2].
  • Hydropathy analysis of KCC1 indicates structural homology to NKCC, including 12 transmembrane domains, a large extracellular loop with potential N-linked glycosylation sites, and cytoplasmic N- and C-terminal regions [3].
  • KCC1 was identified by searching the human expressed sequence tag data base, based on the expectation that it would be distantly related to the Na-K-Cl cotransporter [3].

Biological context of SLC12A4


Anatomical context of SLC12A4


Associations of SLC12A4 with chemical compounds

  • Mutation of the Y1087 congener in KCC1 to aspartate also dramatically inhibited cotransporter activity [11].

Other interactions of SLC12A4

  • Of the four KCC genes known to encode the respective proteins and their spliced variants, RT-PCR with both rat and human primers revealed the predicted cDNA fragments of KCC1, KCC3a, KCC3b, and KCC4 but not KCC2 in both HLE-B3 cells and in human lens tissue extracts from cataractous patients [12].
  • A few reports indicate that the NO/cGMP/PKG signaling pathway regulates KCC1 and KCC3 mRNA expression in VSMCs at the post-transcriptional level [13].

Analytical, diagnostic and therapeutic context of SLC12A4

  • This study investigates the cellular localization of KCC1 by confocal microscopy, activation of K-Cl COT by various non-osmotic and osmotic interventions with net unidirectional K and Rb fluxes at 37( degrees )C, and the effect of Ctd deletion on K-Cl COT regulation [6].


  1. Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element. Zhou, G.P., Wong, C., Su, R., Crable, S.C., Anderson, K.P., Gallagher, P.G. Blood (2004) [Pubmed]
  2. KCl cotransport is an important modulator of human cervical cancer growth and invasion. Shen, M.R., Chou, C.Y., Hsu, K.F., Hsu, Y.M., Chiu, W.T., Tang, M.J., Alper, S.L., Ellory, J.C. J. Biol. Chem. (2003) [Pubmed]
  3. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. Gillen, C.M., Brill, S., Payne, J.A., Forbush, B. J. Biol. Chem. (1996) [Pubmed]
  4. Mapping of equine potassium chloride co-transporter (SLC12A4) and amino acid transporter (SLC7A10) and preliminary studies on associations between SNPs from SLC12A4, SLC7A10 and SLC7A9 and osmotic fragility of erythrocytes. Hanzawa, K., Lear, T.L., Piumi, F., Bailey, E. Anim. Genet. (2002) [Pubmed]
  5. Multiple isoforms of the KC1 cotransporter are expressed in sickle and normal erythroid cells. Crable, S.C., Hammond, S.M., Papes, R., Rettig, R.K., Zhou, G.P., Gallagher, P.G., Joiner, C.H., Anderson, K.P. Exp. Hematol. (2005) [Pubmed]
  6. K-Cl cotransport: immunohistochemical and ion flux studies in human embryonic kidney (HEK293) cells transfected with full-length and C-terminal-domain-truncated KCC1 cDNAs. Lauf, P.K., Zhang, J., Gagnon, K.B., Delpire, E., Fyffe, R.E., Adragna, N.C. Cell. Physiol. Biochem. (2001) [Pubmed]
  7. Influence of K-Cl cotransporter activity on activation of volume-sensitive Cl- channels in human osteoblasts. Bräuer, M., Frei, E., Claes, L., Grissmer, S., Jäger, H. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  8. KCC3 and KCC4 expression in rat adult forebrain. Le Rouzic, P., Ivanov, T.R., Stanley, P.J., Baudoin, F.M., Chan, F., Pinteaux, E., Brown, P.D., Luckman, S.M. Brain Res. (2006) [Pubmed]
  9. Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells. Pellegrino, C.M., Rybicki, A.C., Musto, S., Nagel, R.L., Schwartz, R.S. Blood Cells Mol. Dis. (1998) [Pubmed]
  10. Molecular identification of K-CL cotransporter in dog erythroid progenitor cells. Ochiai, H., Higa, K., Fujise, H. J. Biochem. (2004) [Pubmed]
  11. Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus tyrosine residue. Strange, K., Singer, T.D., Morrison, R., Delpire, E. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  12. KCC isoforms in a human lens epithelial cell line (B3) and lens tissue extracts. Misri, S., Chimote, A.A., Adragna, N.C., Warwar, R., Brown, T.L., Lauf, P.K. Exp. Eye Res. (2006) [Pubmed]
  13. Regulation of K-Cl cotransport: from function to genes. Adragna, N.C., Fulvio, M.D., Lauf, P.K. J. Membr. Biol. (2004) [Pubmed]
WikiGenes - Universities