Recombinant Human Solute carrier family 12 member 6 (SLC12A6), partial

1. Neurodegenerative deficits in hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3. PMID: 27230413
2. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration. PMID: 27485015
3. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC. PMID: 25110711
4. SPAK may promote KCC3-mediated cervix tumor aggressiveness via the NF-kappaB/p38 MAPK/MMP2 axis. PMID: 24655550
5. SLC12A6 has been shown to be causative in Andermann Syndrome. PMID: 24341143
6. serine residue 96 of human KCC3 is a third site that has to be dephosphorylated for full activation of the cotransporter during hypotonicity. PMID: 24043619
7. mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations. PMID: 21628467
8. Neuropathic features of hereditary motor and sensory neuropathy/agenesis of corpus callosum in transgenic mouse lines are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression. PMID: 22423107
9. The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. PMID: 21613606
10. KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity PMID: 21733850
11. mutations of the KCC3 gene may result in non-syndromic childhood onset of demyelinating hereditary motor and sensory neuropathy PMID: 20020398
12. human osteoblasts express functional K-Cl cotransporters in their cell membrane that seem to be able to induce the indirect activation of volume-sensitive Cl- channels by KCl through an increase in the intracellular ions, water influx and cell swelling. PMID: 12637262
13. all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote NH4(+) translocation, presumably through binding of the ion at the K(+) site PMID: 12657561
14. KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers. PMID: 15262997
15. Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. PMID: 16606917
16. Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression. PMID: 17133354
17. KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin. PMID: 17893295
18. KCC3 down-regulates E-cadherin/beta-catenin complex formation by inhibiting transcription of E-cadherin gene and accelerating proteosome-dependent degradation of beta-catenin protein PMID: 18006853
19. study provides evidence that the upstream SLC12A6 G/A promoter SNP is functional not only by changing the DNA primary structure but also by influencing the allelic epigenotype and consequently by influencing the chromatin organization PMID: 18536702
20. Using a yeast 2-hybrid it was discovered that the C-terminal domain of KCC3, that is lost in most hereditary motor and sensory neuropathy with agenesis of the corpus callosum-causing mutations, directly interacts with brain-specific creatine kinase. PMID: 18566107
21. Study identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. PMID: 19665974

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HGNC: 10914

OMIM: 218000

KEGG: hsa:9990

STRING: 9606.ENSP00000452776

UniGene: Hs.510939