Property Summary

NCBI Gene PubMed Count 43
PubMed Score 352.63
PubTator Score 155.75

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (14)

Disease log2 FC p
astrocytoma -3.100 1.8e-03
ependymoma -5.900 3.0e-28
oligodendroglioma -3.100 1.7e-16
glioblastoma -5.000 4.1e-07
sonic hedgehog group medulloblastoma -5.600 1.3e-12
atypical teratoid/rhabdoid tumor -4.800 3.1e-14
medulloblastoma, large-cell -4.600 3.0e-08
primitive neuroectodermal tumor -3.400 1.1e-03
pediatric high grade glioma -4.900 1.4e-10
pilocytic astrocytoma -5.900 1.5e-14
subependymal giant cell astrocytoma -4.225 1.7e-02
Pick disease -1.800 3.0e-02
ovarian cancer 1.900 5.1e-10
pituitary cancer 2.200 7.8e-07

MLP Assay (9)

AID Type Active / Inconclusive / Inactive Description
1456 other 4127 / 0 / 185148 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Primary Screen
1713 other 546 / 325 / 2824 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Secondary Assay with KCC2 cells
1714 other 1815 / 313 / 1567 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Secondary Assay 3 with KCC2 cells
1715 other 867 / 371 / 2457 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Secondary Assay 2 with KCC2 cells
1723 confirmatory 8 / 17 / 37 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Dose-Dependent Assay 2 with KCC2
1734 confirmatory 22 / 0 / 4 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Rubidium Flux
1736 confirmatory 92 / 204 / 313 Identification of Novel Modulators of Cl- dependent Transport Process via HTS; Dose-dependent Assay with KCC2
1737 confirmatory 3 / 9 / 50 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Dose-dependent Assay 3 with KCC2
1799 summary 1 / 0 / 0 Identification of Novel Modulators of Cl- dependent Transport Process via HTS: Antagonist Probe Summary

Gene RIF (32)

PMID Text
26733678 the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms.
26333769 A KCC2 mutation causes epilepsy of infancy with migrating focal seizures. Decreased KCC2 expression, reduced protein glycosylation and impaired Cl- extrusion contribute to loss of KCC2 activity, impairing synaptic inhibition and promoting excitability.
26126716 these data provide insight into the mechanism regulating Cl(-) homeostasis in immature neurons, and suggest that WNK1-regulated changes in KCC2 phosphorylation contribute to the developmental excitatory-to-inhibitory GABA sequence.
26056138 a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.
25947013 SLC12A5 plays a pivotal oncogenic role in colorectal carcinogenesis; its overexpression is an independent prognostic factor of patients with CRC.
24928908 These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE.
24699064 Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer.
24668262 KCC2-R952H from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.
23894354 Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.
23621303 Disrupted KCC2 activity seems to be involved in neuropathic pain, epilepsy, motor spasticity, stress and schizophrenia.
23440186 BPA can disrupt Kcc2 gene expression through epigenetic mechanisms
22496567 Alternate transcripts from KCC2 may participate in the abnormal GABA signaling in the dorsolateral prefrontal cortex associated with schizophrenia
22082832 Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential.
21911617 KCC2 is widely expressed in several human cancer cell lines and serves to increase cervical tumourigenesis via an ion transport-independent mechanism
21613606 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.
21256718 levels of KCC2 mRNA and protein were significantly decreased in the neurons around large abnormal neurons in focal cortical dysplasia
20650312 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20516068 analysis of differences in large extracellular loop between the K(+)-Cl(-) cotransporters KCC2 and KCC4
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19686239 membrane rafts render KCC2 inactive and NKCC1 active
19307176 the two isoforms can be coimmunoprecipitated from the neonatal brain, suggesting the presence of endogenous KCC2a-KCC2b heteromers.
18978678 Observational study of gene-disease association. (HuGE Navigator)
18602983 Observational study of gene-disease association. (HuGE Navigator)
17715129 The novel KCC2a isoform differs from the only previously known KCC2 isoform (now termed KCC2b) by 40 unique N-terminal amino acid residues, including a putative Ste20-related proline alanine-rich kinase-binding site.
17693402 PKC-dependent phosphorylation of KCC2 may play a central role in modulating both the functional expression of this critical transporter in the brain and the strength of synaptic inhibition
16324114 decrease in the spontaneous activity transients was associated with a developmental up-regulation of the neuronal chloride extruder K+-Cl- cotransporter 2
16291749 constitutive K(+)-Cl(-) cotransport mediated by KCC2 is completely independent of serine-threonine phosphatase activity
15932617 KCC2 expression is not only necessary but is also sufficient for ending the depolarizing period of GABA in developing cortical neurons
15528236 GABAergic transmission is influenced by the neuronal expression chloride-extruding K(+)-Cl(-) cotransporter KCC2--REVIEW
12637262 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.
12106695 Expression of hKCC2 cRNA in Xenopus laevis oocytes results in significant Cl(-)-dependent (86)Rb(+) uptake under isotonic conditions
11701957 chromosome 20 mapping

AA Sequence

MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVKGDGNPKESSPFINSTDTEKGKEYDGKNMAL      1 - 70
FEEEMDTSPMVSSLLSGLANYTNLPQGSREHEEAENNEGGKKKPVQAPRMGTFMGVYLPCLQNIFGVILF     71 - 140
LRLTWVVGIAGIMESFCMVFICCSCTMLTAISMSAIATNGVVPAGGSYYMISRSLGPEFGGAVGLCFYLG    141 - 210
TTFAGAMYILGTIEILLAYLFPAMAIFKAEDASGEAAAMLNNMRVYGTCVLTCMATVVFVGVKYVNKFAL    211 - 280
VFLGCVILSILAIYAGVIKSAFDPPNFPICLLGNRTLSRHGFDVCAKLAWEGNETVTTRLWGLFCSSRFL    281 - 350
NATCDEYFTRNNVTEIQGIPGAASGLIKENLWSSYLTKGVIVERSGMTSVGLADGTPIDMDHPYVFSDMT    351 - 420
SYFTLLVGIYFPSVTGIMAGSNRSGDLRDAQKSIPTGTILAIATTSAVYISSVVLFGACIEGVVLRDKFG    421 - 490
EAVNGNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAISRDGIVPFLQVFGHGKANGEPTWA    491 - 560
LLLTACICEIGILIASLDEVAPILSMFFLMCYMFVNLACAVQTLLRTPNWRPRFRYYHWTLSFLGMSLCL    561 - 630
ALMFICSWYYALVAMLIAGLIYKYIEYRGAEKEWGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVL    631 - 700
VRVDQDQNVVHPQLLSLTSQLKAGKGLTIVGSVLEGTFLENHPQAQRAEESIRRLMEAEKVKGFCQVVIS    701 - 770
SNLRDGVSHLIQSGGLGGLQHNTVLVGWPRNWRQKEDHQTWRNFIELVRETTAGHLALLVTKNVSMFPGN    771 - 840
PERFSEGSIDVWWIVHDGGMLMLLPFLLRHHKVWRKCKMRIFTVAQMDDNSIQMKKDLTTFLYHLRITAE    841 - 910
VEVVEMHESDISAYTYEKTLVMEQRSQILKQMHLTKNEREREIQSITDESRGSIRRKNPANTRLRLNVPE    911 - 980
ETAGDSEEKPEEEVQLIHDQSAPSCPSSSPSPGEEPEGEGETDPEKVHLTWTKDKSVAEKNKGPSPVSSE    981 - 1050
GIKDFFSMKPEWENLNQSNVRRMHTAVRLNEVIVKKSRDAKLVLLNMPGPPRNRNGDENYMEFLEVLTEH   1051 - 1120
LDRVMLVRGGGREVITIYS                                                      1121 - 1139
//

Text Mined References (46)

PMID Year Title
26733678 2016 KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.
26528127 2015 Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia.
26333769 2015 Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.
26126716 2015 WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons.
26056138 2015 KCC2 regulates actin dynamics in dendritic spines via interaction with ?-PIX.
25947013 2016 Increased expression of Solute carrier family 12 member 5 via gene amplification contributes to tumour progression and metastasis and associates with poor survival in colorectal cancer.
24928908 2014 Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy.
24699064 2014 Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing.
24668262 2014 A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.
24393035 2014 The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters.
23894354 2013 Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome.
23621303 2013 Treating pathological pain: is KCC2 the key to the gate?
23440186 2013 Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter.
22496567 2012 Transcript-specific associations of SLC12A5 (KCC2) in human prefrontal cortex with development, schizophrenia, and affective disorders.
22082832 Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential.
21911617 2011 The potassium-chloride cotransporter 2 promotes cervical cancer cell migration and invasion by an ion transport-independent mechanism.
21613606 2011 Similar effects of all WNK3 variants on SLC12 cotransporters.
21256718 2011 KCC2 was downregulated in small neurons localized in epileptogenic human focal cortical dysplasia.
20650312 2010 Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans.
20516068 2010 Differences in the large extracellular loop between the K(+)-Cl(-) cotransporters KCC2 and KCC4.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
19686239 2009 Opposite effect of membrane raft perturbation on transport activity of KCC2 and NKCC1.
19307176 2009 Coexpression and heteromerization of two neuronal K-Cl cotransporter isoforms in neonatal brain.
18978678 2008 Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts.
18602983 2008 Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1.
18391953 2008 Rare independent mutations in renal salt handling genes contribute to blood pressure variation.
17715129 2007 A novel N-terminal isoform of the neuron-specific K-Cl cotransporter KCC2.
17693402 2007 Direct protein kinase C-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter KCC2.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16324114 2005 Slow endogenous activity transients and developmental expression of K+-Cl- cotransporter 2 in the immature human cortex.
16291749 2006 A C-terminal domain in KCC2 confers constitutive K+-Cl- cotransport.
15932617 2005 KCC2 expression in immature rat cortical neurons is sufficient to switch the polarity of GABA responses.
15528236 2005 Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12739168 2004 Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family.
12637262 2003 Influence of K-Cl cotransporter activity on activation of volume-sensitive Cl- channels in human osteoblasts.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12106695 2002 Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter.
11780052 2001 The DNA sequence and comparative analysis of human chromosome 20.
11701957 2001 Chromosomal localization of SLC12A5/Slc12a5, the human and mouse genes for the neuron-specific K(+)-Cl(-) cotransporter (KCC2) defines a new region of conserved homology.
11395011 2001 Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition.
10574461 1999 Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.
9110174 1997 Large-scale concatenation cDNA sequencing.
8619474 1996 A "double adaptor" method for improved shotgun library construction.