Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Chloride channel protein 1

Gene

CLCN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei189ChlorideBy similarity1
Binding sitei484Chloride; via amide nitrogenBy similarity1
Binding sitei578ChlorideBy similarity1

GO - Molecular functioni

  • chloride ion binding Source: GO_Central
  • protein homodimerization activity Source: UniProtKB
  • voltage-gated chloride channel activity Source: UniProtKB

GO - Biological processi

  • chloride transmembrane transport Source: UniProtKB
  • ion transmembrane transport Source: Reactome
  • muscle contraction Source: UniProtKB
  • neuronal action potential propagation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

BioCyciZFISH:G66-31329-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Protein family/group databases

TCDBi2.A.49.2.1. the chloride carrier/channel (clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride channel protein 1
Short name:
ClC-1
Alternative name(s):
Chloride channel protein, skeletal muscle
Gene namesi
Name:CLCN1
Synonyms:CLC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2019. CLCN1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 114CytoplasmicBy similarityAdd BLAST114
Transmembranei115 – 152HelicalBy similarityAdd BLAST38
Transmembranei159 – 182HelicalBy similarityAdd BLAST24
Intramembranei191 – 198HelicalBy similarity8
Transmembranei207 – 225HelicalBy similarityAdd BLAST19
Transmembranei232 – 250HelicalBy similarityAdd BLAST19
Intramembranei266 – 278HelicalBy similarityAdd BLAST13
Intramembranei282 – 290HelicalBy similarity9
Transmembranei302 – 321HelicalBy similarityAdd BLAST20
Transmembranei348 – 376HelicalBy similarityAdd BLAST29
Transmembranei385 – 404HelicalBy similarityAdd BLAST20
Transmembranei454 – 474HelicalBy similarityAdd BLAST21
Transmembranei482 – 505HelicalBy similarityAdd BLAST24
Intramembranei522 – 536HelicalBy similarityAdd BLAST15
Intramembranei537 – 538Note=Loop between two helicesBy similarity2
Intramembranei539 – 550HelicalBy similarityAdd BLAST12
Intramembranei551 – 555Note=Loop between two helicesBy similarity5
Transmembranei556 – 573HelicalBy similarityAdd BLAST18
Topological domaini574 – 988CytoplasmicBy similarityAdd BLAST415

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Myotonia congenita, autosomal dominant (MCAD)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior).
See also OMIM:160800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075591128M → V in MCAD. 1 PublicationCorresponds to variant rs80356699dbSNPEnsembl.1
Natural variantiVAR_001586161F → V in MCAD and MCAR. 1 Publication1
Natural variantiVAR_075597193E → K in MCAD. 1 PublicationCorresponds to variant rs80356686dbSNPEnsembl.1
Natural variantiVAR_075599198L → P in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel. 1 Publication1
Natural variantiVAR_001589200G → R in MCAD and MCAR. 1 Publication1
Natural variantiVAR_001590230G → E in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect. 3 PublicationsCorresponds to variant rs80356700dbSNPEnsembl.1
Natural variantiVAR_001594286V → A in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dominant negative effect. 1 PublicationCorresponds to variant rs80356689dbSNPEnsembl.1
Natural variantiVAR_001595290I → M in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect. 2 PublicationsCorresponds to variant rs80356690dbSNPEnsembl.1
Natural variantiVAR_001598307F → S in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect. 2 PublicationsCorresponds to variant rs80356701dbSNPEnsembl.1
Natural variantiVAR_001599313A → T in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356692dbSNPEnsembl.1
Natural variantiVAR_001600317R → Q in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel. 2 PublicationsCorresponds to variant rs80356702dbSNPEnsembl.1
Natural variantiVAR_001603338R → Q in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356703dbSNPEnsembl.1
Natural variantiVAR_001607480P → L in MCAD; loss of chloride transport; changed chloride channel activity; changed gating of the channel; dominant effect. 3 PublicationsCorresponds to variant rs80356694dbSNPEnsembl.1
Natural variantiVAR_075605484F → L in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect. 1 Publication1
Natural variantiVAR_001611552Q → R in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect. 3 PublicationsCorresponds to variant rs80356696dbSNPEnsembl.1
Natural variantiVAR_001612556I → N in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; partial dominant negative effect. 2 PublicationsCorresponds to variant rs80356697dbSNPEnsembl.1
Myotonia congenita, autosomal recessive (MCAR)16 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal recessive form (Becker disease) is more severe than the autosomal dominant one (Thomsen disease).
See also OMIM:255700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07558843Q → R in MCAR; decreased chloride transport; decreased localization to the plasma membrane; dominant negative effect on chloride transport and localization to the plasma membrane; no significant effect on chloride channel activity; no effect on homodimerization. 1 Publication1
Natural variantiVAR_07558970S → L in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant rs769312894dbSNPEnsembl.1
Natural variantiVAR_07559082T → A in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant rs772100356dbSNPEnsembl.1
Natural variantiVAR_001582105R → C in MCAR; no effect on chloride transport. 1 PublicationCorresponds to variant rs201509501dbSNPEnsembl.1
Natural variantiVAR_001584136D → G in MCAR. 1 Publication1
Natural variantiVAR_075592137Y → D in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity. 1 PublicationCorresponds to variant rs748639603dbSNPEnsembl.1
Natural variantiVAR_001585150Y → C in MCAR. 1 Publication1
Natural variantiVAR_075594160Q → H in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity. 1 PublicationCorresponds to variant rs771532474dbSNPEnsembl.1
Natural variantiVAR_001586161F → V in MCAD and MCAR. 1 Publication1
Natural variantiVAR_075595164W → R in MCAR; altered chloride channel activity. 1 Publication1
Natural variantiVAR_001587165V → G in MCAR. 1
Natural variantiVAR_001588167F → L in MCAR; no effect on chloride transport. 3 PublicationsCorresponds to variant rs149729531dbSNPEnsembl.1
Natural variantiVAR_075596190G → S in MCAR; loss of chloride channel activity. 3 Publications1
Natural variantiVAR_075598197I → R in MCAR; changed chloride channel activity. 1 Publication1
Natural variantiVAR_001589200G → R in MCAD and MCAR. 1 Publication1
Natural variantiVAR_001590230G → E in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect. 3 PublicationsCorresponds to variant rs80356700dbSNPEnsembl.1
Natural variantiVAR_001591236V → L in MCAR; loss of chloride transport; changed calcium channel activity; changed gating of the channel. 1 Publication1
Natural variantiVAR_001592261Y → C in MCAR. 1 PublicationCorresponds to variant rs200621976dbSNPEnsembl.1
Natural variantiVAR_075600270G → V in MCAR; decreased chloride channel activity. 1 Publication1
Natural variantiVAR_075601277C → R in MCAR; reduced chloride transport; no effect on protein abundance. 1 PublicationCorresponds to variant rs757109632dbSNPEnsembl.1
Natural variantiVAR_075602277C → Y in MCAR; reduced chloride transport; changed calcium channel activity; changed gating of the channel; no effect on protein abundance. 1 Publication1
Natural variantiVAR_001593285G → E in MCAR; loss of chloride channel activity. 2 PublicationsCorresponds to variant rs150885084dbSNPEnsembl.1
Natural variantiVAR_001596291E → K in MCAR; loss of calcium channel activity; no dominant negative effect. 2 PublicationsCorresponds to variant rs121912805dbSNPEnsembl.1
Natural variantiVAR_001599313A → T in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356692dbSNPEnsembl.1
Natural variantiVAR_001601327V → I in MCAR. Corresponds to variant rs774396430dbSNPEnsembl.1
Natural variantiVAR_001602329I → T in MCAR. 1
Natural variantiVAR_001603338R → Q in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356703dbSNPEnsembl.1
Natural variantiVAR_075603412Q → P in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded. 1 Publication1
Natural variantiVAR_001604413F → C in MCAR. 1 PublicationCorresponds to variant rs121912799dbSNPEnsembl.1
Natural variantiVAR_001605415A → V in MCAR. 1 Publication1
Natural variantiVAR_075604453R → W in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant rs376026619dbSNPEnsembl.1
Natural variantiVAR_001608482G → R in MCAR. Corresponds to variant rs746125212dbSNPEnsembl.1
Natural variantiVAR_001609485M → V in MCAR. 1 PublicationCorresponds to variant rs146457619dbSNPEnsembl.1
Natural variantiVAR_001610496R → S in MCAR; loss of chloride channel activity; recessive. 2 PublicationsCorresponds to variant rs121912801dbSNPEnsembl.1
Natural variantiVAR_075606499G → R in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating. 1 PublicationCorresponds to variant rs121912807dbSNPEnsembl.1
Natural variantiVAR_075607527I → T in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075608533T → I in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075609536V → L in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_001611552Q → R in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect. 3 PublicationsCorresponds to variant rs80356696dbSNPEnsembl.1
Natural variantiVAR_001612556I → N in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; partial dominant negative effect. 2 PublicationsCorresponds to variant rs80356697dbSNPEnsembl.1
Natural variantiVAR_001613563V → I in MCAR. 1 Publication1
Natural variantiVAR_075611628L → P in MCAR; unknown pathological significance; no effect on calcium channel activity. 1 Publication1
Natural variantiVAR_075612640V → G in MCAR; reduced calcium channel activity. 1 Publication1
Natural variantiVAR_001614708F → L in MCAR. 1 Publication1
Natural variantiVAR_075613845G → S in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant rs755433272dbSNPEnsembl.1
Natural variantiVAR_075614855G → E in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075615932P → L in MCAR; unknown pathological significance. 1 PublicationCorresponds to variant rs80356706dbSNPEnsembl.1
Natural variantiVAR_075616947V → E in MCAR; unknown pathological significance. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi290I → C, E, F, G, K, L, Q, T, V or Y: Changed chloride channel activity; changed gating of the channel. 1 Publication1
Mutagenesisi291E → D: No effect on calcium channel activity. 1 Publication1
Mutagenesisi291E → L: Loss of calcium channel activity. 1 Publication1
Mutagenesisi496R → K: Changed gating of the channel. 1 Publication1
Mutagenesisi499G → K or E: Changed gating of the channel. 1 Publication1
Mutagenesisi499G → Q: No effect on gating of the channel. 1 Publication1
Mutagenesisi500E → Q: No effect on channel function. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1180.
MalaCardsiCLCN1.
MIMi160800. phenotype.
255700. phenotype.
OpenTargetsiENSG00000188037.
Orphaneti614. Thomsen and Becker disease.
PharmGKBiPA26546.

Polymorphism and mutation databases

BioMutaiCLCN1.
DMDMi311033468.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944291 – 988Chloride channel protein 1Add BLAST988

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei886PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP35523.
PaxDbiP35523.
PeptideAtlasiP35523.
PRIDEiP35523.

PTM databases

iPTMnetiP35523.
PhosphoSitePlusiP35523.

Expressioni

Tissue specificityi

Predominantly expressed in skeletal muscles.

Gene expression databases

BgeeiENSG00000188037.
CleanExiHS_CLCN1.
ExpressionAtlasiP35523. baseline and differential.
GenevisibleiP35523. HS.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926245EBI-10206780,EBI-743771
FAM9BQ8IZU03EBI-10206780,EBI-10175124

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi107594. 7 interactors.
IntActiP35523. 2 interactors.
STRINGi9606.ENSP00000339867.

Chemistry databases

BindingDBiP35523.

Structurei

3D structure databases

ProteinModelPortaliP35523.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini609 – 668CBS 1PROSITE-ProRule annotationAdd BLAST60
Domaini821 – 876CBS 2PROSITE-ProRule annotationAdd BLAST56

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi188 – 192Selectivity filter part_1By similarity5
Motifi230 – 234Selectivity filter part_2By similarity5
Motifi482 – 486Selectivity filter part_3By similarity5

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0476. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000231297.
HOVERGENiHBG005332.
InParanoidiP35523.
KOiK05010.
OMAiDMLTVGC.
OrthoDBiEOG091G01RJ.
PhylomeDBiP35523.
TreeFamiTF352264.

Family and domain databases

Gene3Di1.10.3080.10. 1 hit.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002243. Cl_channel-1.
[Graphical view]
PfamiPF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01112. CLCHANNEL1.
SUPFAMiSSF81340. SSF81340. 1 hit.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35523-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQSRSQQRG GEQSWWGSDP QYQYMPFEHC TSYGLPSENG GLQHRLRKDA
60 70 80 90 100
GPRHNVHPTQ IYGHHKEQFS DREQDIGMPK KTGSSSTVDS KDEDHYSKCQ
110 120 130 140 150
DCIHRLGQVV RRKLGEDGIF LVLLGLLMAL VSWSMDYVSA KSLQAYKWSY
160 170 180 190 200
AQMQPSLPLQ FLVWVTFPLV LILFSALFCH LISPQAVGSG IPEMKTILRG
210 220 230 240 250
VVLKEYLTMK AFVAKVVALT AGLGSGIPVG KEGPFVHIAS ICAAVLSKFM
260 270 280 290 300
SVFCGVYEQP YYYSDILTVG CAVGVGCCFG TPLGGVLFSI EVTSTYFAVR
310 320 330 340 350
NYWRGFFAAT FSAFVFRVLA VWNKDAVTIT ALFRTNFRMD FPFDLKELPA
360 370 380 390 400
FAAIGICCGL LGAVFVYLHR QVMLGVRKHK ALSQFLAKHR LLYPGIVTFV
410 420 430 440 450
IASFTFPPGM GQFMAGELMP REAISTLFDN NTWVKHAGDP ESLGQSAVWI
460 470 480 490 500
HPRVNVVIII FLFFVMKFWM SIVATTMPIP CGGFMPVFVL GAAFGRLVGE
510 520 530 540 550
IMAMLFPDGI LFDDIIYKIL PGGYAVIGAA ALTGAVSHTV STAVICFELT
560 570 580 590 600
GQIAHILPMM VAVILANMVA QSLQPSLYDS IIQVKKLPYL PDLGWNQLSK
610 620 630 640 650
YTIFVEDIMV RDVKFVSASY TYGELRTLLQ TTTVKTLPLV DSKDSMILLG
660 670 680 690 700
SVERSELQAL LQRHLCPERR LRAAQEMARK LSELPYDGKA RLAGEGLPGA
710 720 730 740 750
PPGRPESFAF VDEDEDEDLS GKSELPPSLA LHPSTTAPLS PEEPNGPLPG
760 770 780 790 800
HKQQPEAPEP AGQRPSIFQS LLHCLLGRAR PTKKKTTQDS TDLVDNMSPE
810 820 830 840 850
EIEAWEQEQL SQPVCFDSCC IDQSPFQLVE QTTLHKTHTL FSLLGLHLAY
860 870 880 890 900
VTSMGKLRGV LALEELQKAI EGHTKSGVQL RPPLASFRNT TSTRKSTGAP
910 920 930 940 950
PSSAENWNLP EDRPGATGTG DVIAASPETP VPSPSPEPPL SLAPGKVEGE
960 970 980
LEELELVESP GLEEELADIL QGPSLRSTDE EDEDELIL
Length:988
Mass (Da):108,626
Last modified:November 2, 2010 - v3
Checksum:iCA838BCD2AF3CA68
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti697L → P in CAA80996 (PubMed:8112288).Curated1
Sequence conflicti697L → P in CAA81103 (PubMed:8112288).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07558843Q → R in MCAR; decreased chloride transport; decreased localization to the plasma membrane; dominant negative effect on chloride transport and localization to the plasma membrane; no significant effect on chloride channel activity; no effect on homodimerization. 1 Publication1
Natural variantiVAR_07558970S → L in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant rs769312894dbSNPEnsembl.1
Natural variantiVAR_07559082T → A in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant rs772100356dbSNPEnsembl.1
Natural variantiVAR_001582105R → C in MCAR; no effect on chloride transport. 1 PublicationCorresponds to variant rs201509501dbSNPEnsembl.1
Natural variantiVAR_001583118G → W.2 PublicationsCorresponds to variant rs10282312dbSNPEnsembl.1
Natural variantiVAR_075591128M → V in MCAD. 1 PublicationCorresponds to variant rs80356699dbSNPEnsembl.1
Natural variantiVAR_001584136D → G in MCAR. 1 Publication1
Natural variantiVAR_075592137Y → D in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity. 1 PublicationCorresponds to variant rs748639603dbSNPEnsembl.1
Natural variantiVAR_001585150Y → C in MCAR. 1 Publication1
Natural variantiVAR_075593154Q → R Polymorphism; no effect on chloride transport. 1 PublicationCorresponds to variant rs111482384dbSNPEnsembl.1
Natural variantiVAR_075594160Q → H in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity. 1 PublicationCorresponds to variant rs771532474dbSNPEnsembl.1
Natural variantiVAR_001586161F → V in MCAD and MCAR. 1 Publication1
Natural variantiVAR_075595164W → R in MCAR; altered chloride channel activity. 1 Publication1
Natural variantiVAR_001587165V → G in MCAR. 1
Natural variantiVAR_001588167F → L in MCAR; no effect on chloride transport. 3 PublicationsCorresponds to variant rs149729531dbSNPEnsembl.1
Natural variantiVAR_075596190G → S in MCAR; loss of chloride channel activity. 3 Publications1
Natural variantiVAR_075597193E → K in MCAD. 1 PublicationCorresponds to variant rs80356686dbSNPEnsembl.1
Natural variantiVAR_075598197I → R in MCAR; changed chloride channel activity. 1 Publication1
Natural variantiVAR_075599198L → P in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel. 1 Publication1
Natural variantiVAR_001589200G → R in MCAD and MCAR. 1 Publication1
Natural variantiVAR_001590230G → E in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect. 3 PublicationsCorresponds to variant rs80356700dbSNPEnsembl.1
Natural variantiVAR_001591236V → L in MCAR; loss of chloride transport; changed calcium channel activity; changed gating of the channel. 1 Publication1
Natural variantiVAR_001592261Y → C in MCAR. 1 PublicationCorresponds to variant rs200621976dbSNPEnsembl.1
Natural variantiVAR_075600270G → V in MCAR; decreased chloride channel activity. 1 Publication1
Natural variantiVAR_075601277C → R in MCAR; reduced chloride transport; no effect on protein abundance. 1 PublicationCorresponds to variant rs757109632dbSNPEnsembl.1
Natural variantiVAR_075602277C → Y in MCAR; reduced chloride transport; changed calcium channel activity; changed gating of the channel; no effect on protein abundance. 1 Publication1
Natural variantiVAR_001593285G → E in MCAR; loss of chloride channel activity. 2 PublicationsCorresponds to variant rs150885084dbSNPEnsembl.1
Natural variantiVAR_001594286V → A in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dominant negative effect. 1 PublicationCorresponds to variant rs80356689dbSNPEnsembl.1
Natural variantiVAR_001595290I → M in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect. 2 PublicationsCorresponds to variant rs80356690dbSNPEnsembl.1
Natural variantiVAR_001596291E → K in MCAR; loss of calcium channel activity; no dominant negative effect. 2 PublicationsCorresponds to variant rs121912805dbSNPEnsembl.1
Natural variantiVAR_001597300R → Q Polymorphism; no effect on chloride transport. 2 PublicationsCorresponds to variant rs118066140dbSNPEnsembl.1
Natural variantiVAR_001598307F → S in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect. 2 PublicationsCorresponds to variant rs80356701dbSNPEnsembl.1
Natural variantiVAR_001599313A → T in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356692dbSNPEnsembl.1
Natural variantiVAR_001600317R → Q in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel. 2 PublicationsCorresponds to variant rs80356702dbSNPEnsembl.1
Natural variantiVAR_001601327V → I in MCAR. Corresponds to variant rs774396430dbSNPEnsembl.1
Natural variantiVAR_001602329I → T in MCAR. 1
Natural variantiVAR_001603338R → Q in MCAD and MCAR. 1 PublicationCorresponds to variant rs80356703dbSNPEnsembl.1
Natural variantiVAR_075603412Q → P in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded. 1 Publication1
Natural variantiVAR_001604413F → C in MCAR. 1 PublicationCorresponds to variant rs121912799dbSNPEnsembl.1
Natural variantiVAR_001605415A → V in MCAR. 1 Publication1
Natural variantiVAR_001606437A → T Polymorphism. 1 PublicationCorresponds to variant rs41276054dbSNPEnsembl.1
Natural variantiVAR_075604453R → W in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant rs376026619dbSNPEnsembl.1
Natural variantiVAR_001607480P → L in MCAD; loss of chloride transport; changed chloride channel activity; changed gating of the channel; dominant effect. 3 PublicationsCorresponds to variant rs80356694dbSNPEnsembl.1
Natural variantiVAR_001608482G → R in MCAR. Corresponds to variant rs746125212dbSNPEnsembl.1
Natural variantiVAR_075605484F → L in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect. 1 Publication1
Natural variantiVAR_001609485M → V in MCAR. 1 PublicationCorresponds to variant rs146457619dbSNPEnsembl.1
Natural variantiVAR_001610496R → S in MCAR; loss of chloride channel activity; recessive. 2 PublicationsCorresponds to variant rs121912801dbSNPEnsembl.1
Natural variantiVAR_075606499G → R in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating. 1 PublicationCorresponds to variant rs121912807dbSNPEnsembl.1
Natural variantiVAR_075607527I → T in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075608533T → I in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075609536V → L in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_036300548E → K in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs546411827dbSNPEnsembl.1
Natural variantiVAR_001611552Q → R in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect. 3 PublicationsCorresponds to variant rs80356696dbSNPEnsembl.1
Natural variantiVAR_001612556I → N in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; partial dominant negative effect. 2 PublicationsCorresponds to variant rs80356697dbSNPEnsembl.1
Natural variantiVAR_001613563V → I in MCAR. 1 Publication1
Natural variantiVAR_075610614K → N Polymorphism. 1 PublicationCorresponds to variant rs140205115dbSNPEnsembl.1
Natural variantiVAR_075611628L → P in MCAR; unknown pathological significance; no effect on calcium channel activity. 1 Publication1
Natural variantiVAR_075612640V → G in MCAR; reduced calcium channel activity. 1 Publication1
Natural variantiVAR_001614708F → L in MCAR. 1 Publication1
Natural variantiVAR_047779727P → L.Corresponds to variant rs13438232dbSNPEnsembl.1
Natural variantiVAR_075613845G → S in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant rs755433272dbSNPEnsembl.1
Natural variantiVAR_075614855G → E in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_075615932P → L in MCAR; unknown pathological significance. 1 PublicationCorresponds to variant rs80356706dbSNPEnsembl.1
Natural variantiVAR_075616947V → E in MCAR; unknown pathological significance. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z25587 Genomic DNA. Translation: CAA80996.1.
Z25884 mRNA. Translation: CAA81103.1.
CH236959 Genomic DNA. Translation: EAL23786.1.
BC112156 mRNA. Translation: AAI12157.1.
BC113495 mRNA. Translation: AAI13496.1.
M97820 mRNA. No translation available.
L08261 Genomic DNA. No translation available.
L08262 Genomic DNA. No translation available.
L08263 Genomic DNA. No translation available.
L08264 Genomic DNA. No translation available.
L08265 Genomic DNA. No translation available.
Z25753
, Z25754, Z25755, Z25756, Z25757, Z25758, Z25759, Z25760, Z25761, Z25762, Z25763, Z25764, Z25765, Z25766, Z25767, Z25752 Genomic DNA. Translation: CAB56792.1.
Z25768, Z25872 Genomic DNA. Translation: CAB56814.1.
CCDSiCCDS5881.1.
PIRiS37078.
RefSeqiNP_000074.2. NM_000083.2.
UniGeneiHs.121483.

Genome annotation databases

EnsembliENST00000343257; ENSP00000339867; ENSG00000188037.
GeneIDi1180.
KEGGihsa:1180.
UCSCiuc003wcr.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z25587 Genomic DNA. Translation: CAA80996.1.
Z25884 mRNA. Translation: CAA81103.1.
CH236959 Genomic DNA. Translation: EAL23786.1.
BC112156 mRNA. Translation: AAI12157.1.
BC113495 mRNA. Translation: AAI13496.1.
M97820 mRNA. No translation available.
L08261 Genomic DNA. No translation available.
L08262 Genomic DNA. No translation available.
L08263 Genomic DNA. No translation available.
L08264 Genomic DNA. No translation available.
L08265 Genomic DNA. No translation available.
Z25753
, Z25754, Z25755, Z25756, Z25757, Z25758, Z25759, Z25760, Z25761, Z25762, Z25763, Z25764, Z25765, Z25766, Z25767, Z25752 Genomic DNA. Translation: CAB56792.1.
Z25768, Z25872 Genomic DNA. Translation: CAB56814.1.
CCDSiCCDS5881.1.
PIRiS37078.
RefSeqiNP_000074.2. NM_000083.2.
UniGeneiHs.121483.

3D structure databases

ProteinModelPortaliP35523.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107594. 7 interactors.
IntActiP35523. 2 interactors.
STRINGi9606.ENSP00000339867.

Chemistry databases

BindingDBiP35523.

Protein family/group databases

TCDBi2.A.49.2.1. the chloride carrier/channel (clc) family.

PTM databases

iPTMnetiP35523.
PhosphoSitePlusiP35523.

Polymorphism and mutation databases

BioMutaiCLCN1.
DMDMi311033468.

Proteomic databases

EPDiP35523.
PaxDbiP35523.
PeptideAtlasiP35523.
PRIDEiP35523.

Protocols and materials databases

DNASUi1180.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343257; ENSP00000339867; ENSG00000188037.
GeneIDi1180.
KEGGihsa:1180.
UCSCiuc003wcr.2. human.

Organism-specific databases

CTDi1180.
DisGeNETi1180.
GeneCardsiCLCN1.
GeneReviewsiCLCN1.
HGNCiHGNC:2019. CLCN1.
MalaCardsiCLCN1.
MIMi118425. gene.
160800. phenotype.
255700. phenotype.
neXtProtiNX_P35523.
OpenTargetsiENSG00000188037.
Orphaneti614. Thomsen and Becker disease.
PharmGKBiPA26546.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0476. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000231297.
HOVERGENiHBG005332.
InParanoidiP35523.
KOiK05010.
OMAiDMLTVGC.
OrthoDBiEOG091G01RJ.
PhylomeDBiP35523.
TreeFamiTF352264.

Enzyme and pathway databases

BioCyciZFISH:G66-31329-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiCLCN1. human.
GeneWikiiCLCN1.
GenomeRNAii1180.
PROiP35523.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188037.
CleanExiHS_CLCN1.
ExpressionAtlasiP35523. baseline and differential.
GenevisibleiP35523. HS.

Family and domain databases

Gene3Di1.10.3080.10. 1 hit.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002243. Cl_channel-1.
[Graphical view]
PfamiPF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01112. CLCHANNEL1.
SUPFAMiSSF81340. SSF81340. 1 hit.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCN1_HUMAN
AccessioniPrimary (citable) accession number: P35523
Secondary accession number(s): A4D2H5, Q2M202
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 2, 2010
Last modified: November 30, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.