Human Gene CLCN6 (uc001ate.5)
  Description: Homo sapiens chloride channel, voltage-sensitive 6 (CLCN6), transcript variant 1, mRNA.
RefSeq Summary (NM_001286): This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012].
Transcript (Including UTRs)
   Position: hg19 chr1:11,866,153-11,903,201 Size: 37,049 Total Exon Count: 23 Strand: +
Coding Region
   Position: hg19 chr1:11,866,320-11,900,280 Size: 33,961 Coding Exon Count: 23 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:11,866,153-11,903,201)mRNA (may differ from genome)Protein (869 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuman Cortex Gene ExpressionLynx
MGIneXtProtOMIMPubMedReactomeUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: CLCN6_HUMAN
DESCRIPTION: RecName: Full=Chloride transport protein 6; AltName: Full=Chloride channel protein 6; Short=ClC-6;
FUNCTION: Chloride transport protein, initially identified as voltage-gated chloride channel. The presence of the conserved gating glutamate residues suggests that is functions as antiporter.
SUBCELLULAR LOCATION: Endosome membrane; Multi-pass membrane protein. Note=Detected in detergent-resistant lipid rafts.
TISSUE SPECIFICITY: Testis, ovary, small intestine, brain and skeletal muscle. Low level expression in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Isoform C is only detected in kidney.
PTM: N-glycosylated on several asparagine residues.
MISCELLANEOUS: The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).
SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-6/CLCN6 subfamily.
SIMILARITY: Contains 2 CBS domains.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CLCN6
CDC HuGE Published Literature: CLCN6
Positive Disease Associations: Natriuretic Peptide, Brain , systolic blood pressure
Related Studies:
  1. Natriuretic Peptide, Brain
    Fabiola Del Greco M et al. Human molecular genetics 2011, Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster., Human molecular genetics. [PubMed 21273288]
  2. systolic blood pressure
    Newton-Cheh ,et al. 2009, Genome-wide association study identifies eight loci associated with blood pressure, Nature genetics 2009 . [PubMed 19430483]

-  MalaCards Disease Associations
  MalaCards Gene Search: CLCN6
Diseases sorted by gene-association score: benign familial infantile epilepsy (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 17.80 RPKM in Testis
Total median expression: 509.32 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -70.70167-0.423 Picture PostScript Text
3' UTR -1042.572921-0.357 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR014743 - Cl-channel_core
IPR001807 - Cl-channel_volt-gated
IPR002248 - Cl_channel-6
IPR000644 - Cysta_beta_synth_core

Pfam Domains:
PF00571 - CBS domain
PF00654 - Voltage gated chloride channel

SCOP Domains:
54631 - CBS-domain
81340 - Clc chloride channel

ModBase Predicted Comparative 3D Structure on P51797
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005247 voltage-gated chloride channel activity
GO:0005524 ATP binding
GO:0015297 antiporter activity

Biological Process:
GO:0006811 ion transport
GO:0006821 chloride transport
GO:0006884 cell volume homeostasis
GO:0007165 signal transduction
GO:0009612 response to mechanical stimulus
GO:0034220 ion transmembrane transport
GO:0055085 transmembrane transport
GO:1902476 chloride transmembrane transport

Cellular Component:
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  AK289999 - Homo sapiens cDNA FLJ76760 complete cds, highly similar to Homo sapiens chloride channel 6 (CLCN6), transcript variant ClC-6a, mRNA.
D28475 - Homo sapiens KIAA0046 mRNA.
X83378 - H.sapiens mRNA for putative chloride channel.
BC117420 - Homo sapiens chloride channel 6, mRNA (cDNA clone MGC:151029 IMAGE:40125971), complete cds.
BC117424 - Homo sapiens chloride channel 6, mRNA (cDNA clone MGC:151033 IMAGE:40125975), complete cds.
BC143844 - Homo sapiens cDNA clone IMAGE:9052359, containing frame-shift errors.
AK307098 - Homo sapiens cDNA, FLJ97046.
AK294764 - Homo sapiens cDNA FLJ61242 complete cds, highly similar to Chloride channel protein 6.
JD344992 - Sequence 326016 from Patent EP1572962.
JD502786 - Sequence 483810 from Patent EP1572962.
BC050457 - Homo sapiens chloride channel 6, mRNA (cDNA clone IMAGE:6192828), containing frame-shift errors.
X96391 - H.sapiens mRNA for alternatively spliced isoform of CLC-6 chloride channel.
X99475 - H.sapiens mRNA for chloride channel, ClC-6d.
X99473 - H.sapiens mRNA for chloride channel, ClC-6a.
X99474 - H.sapiens mRNA for chloride channel, ClC-6c.
AB383724 - Synthetic construct DNA, clone: pF1KSDA0046, Homo sapiens CLCN6 gene for chloride channel protein 6, complete cds, without stop codon, in Flexi system.
HQ258635 - Synthetic construct Homo sapiens clone IMAGE:100073191 chloride channel 6 (CLCN6), transcript variant ClC-6a (CLCN6) gene, encodes complete protein.
KJ896616 - Synthetic construct Homo sapiens clone ccsbBroadEn_06010 CLCN6 gene, encodes complete protein.
JD026435 - Sequence 7459 from Patent EP1572962.
JD033984 - Sequence 15008 from Patent EP1572962.
JD422912 - Sequence 403936 from Patent EP1572962.
JD480316 - Sequence 461340 from Patent EP1572962.
FJ706070 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.1 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706071 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.2 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706072 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.3 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706073 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.4 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706074 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.5 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706075 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.6 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706076 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.7 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
FJ706077 - Homo sapiens NPPA antisense transcript isoform NPPA-AS.8 antisense RNA (NPPA-AS), partial sequence, alternatively spliced.
JD201678 - Sequence 182702 from Patent EP1572962.
JD420678 - Sequence 401702 from Patent EP1572962.
JD255293 - Sequence 236317 from Patent EP1572962.
JD102638 - Sequence 83662 from Patent EP1572962.
JD068959 - Sequence 49983 from Patent EP1572962.
JD255514 - Sequence 236538 from Patent EP1572962.
JD276021 - Sequence 257045 from Patent EP1572962.
DQ597878 - Homo sapiens piRNA piR-35944, complete sequence.
JD299292 - Sequence 280316 from Patent EP1572962.
JD358598 - Sequence 339622 from Patent EP1572962.
JD291361 - Sequence 272385 from Patent EP1572962.
JD428902 - Sequence 409926 from Patent EP1572962.
JD258301 - Sequence 239325 from Patent EP1572962.
JD404245 - Sequence 385269 from Patent EP1572962.
JD087603 - Sequence 68627 from Patent EP1572962.
JD454506 - Sequence 435530 from Patent EP1572962.
JD206520 - Sequence 187544 from Patent EP1572962.
JD372147 - Sequence 353171 from Patent EP1572962.
JD224852 - Sequence 205876 from Patent EP1572962.
JD369549 - Sequence 350573 from Patent EP1572962.
JD232706 - Sequence 213730 from Patent EP1572962.
JD039697 - Sequence 20721 from Patent EP1572962.
JD390844 - Sequence 371868 from Patent EP1572962.
JD504880 - Sequence 485904 from Patent EP1572962.
JD230508 - Sequence 211532 from Patent EP1572962.
JD271250 - Sequence 252274 from Patent EP1572962.
JD310517 - Sequence 291541 from Patent EP1572962.
JD288189 - Sequence 269213 from Patent EP1572962.
JD173699 - Sequence 154723 from Patent EP1572962.
JD202271 - Sequence 183295 from Patent EP1572962.
JD256422 - Sequence 237446 from Patent EP1572962.
JD276333 - Sequence 257357 from Patent EP1572962.
JD217355 - Sequence 198379 from Patent EP1572962.
JD544553 - Sequence 525577 from Patent EP1572962.
JD097849 - Sequence 78873 from Patent EP1572962.
JD282797 - Sequence 263821 from Patent EP1572962.
JD372422 - Sequence 353446 from Patent EP1572962.
JD203041 - Sequence 184065 from Patent EP1572962.
JD381349 - Sequence 362373 from Patent EP1572962.
JD492622 - Sequence 473646 from Patent EP1572962.
JD391293 - Sequence 372317 from Patent EP1572962.
JD470535 - Sequence 451559 from Patent EP1572962.
JD060368 - Sequence 41392 from Patent EP1572962.
JD120390 - Sequence 101414 from Patent EP1572962.
JD388607 - Sequence 369631 from Patent EP1572962.
JD388608 - Sequence 369632 from Patent EP1572962.
JD521996 - Sequence 503020 from Patent EP1572962.
JD369278 - Sequence 350302 from Patent EP1572962.
JD434366 - Sequence 415390 from Patent EP1572962.
JD036737 - Sequence 17761 from Patent EP1572962.
JD040916 - Sequence 21940 from Patent EP1572962.
JD490681 - Sequence 471705 from Patent EP1572962.
JD236727 - Sequence 217751 from Patent EP1572962.
JD389354 - Sequence 370378 from Patent EP1572962.
JD296315 - Sequence 277339 from Patent EP1572962.
JD535047 - Sequence 516071 from Patent EP1572962.
JD314762 - Sequence 295786 from Patent EP1572962.
JD357266 - Sequence 338290 from Patent EP1572962.
JD087914 - Sequence 68938 from Patent EP1572962.
JD566523 - Sequence 547547 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P51797 (Reactome details) participates in the following event(s):

R-HSA-2730692 CLCN4/5/6 exchange Cl- for H+
R-HSA-6802927 BRAF and RAF fusion mutant dimers are phosphorylated
R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs
R-HSA-6802932 Dissociation of BRAF/RAF fusion complex
R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks
R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers
R-HSA-2672351 Stimuli-sensing channels
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-983712 Ion channel transport
R-HSA-6802957 Oncogenic MAPK signaling
R-HSA-382551 Transport of small molecules
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A8K1T4, CLCN6_HUMAN, KIAA0046, NM_001286, NP_001277, O60818, O60819, O60820, O60821, P51797, P78520, P78521, Q17R81, Q5SNW2, Q5SNW3, Q5SNX1, Q5SNX2, Q5SNX3, Q99427, Q99428, Q99429, uc001ate.4
UCSC ID: uc001ate.5
RefSeq Accession: NM_001286
Protein: P51797 (aka CLCN6_HUMAN or CLC6_HUMAN)
CCDS: CCDS138.1, CCDS57972.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001286.3
exon count: 23CDS single in 3' UTR: no RNA size: 5713
ORF size: 2610CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 5414.00frame shift in genome: no % Coverage: 99.74
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.