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Protein

Chloride channel protein 1

Gene

CLCN1

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

Functioni

Voltage-gated chloride channel (PubMed:8112288, PubMed:9122265, PubMed:12456816). Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction.9 Publications

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.1 Publication

Sites

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

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel, Voltage-gated channel
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000188037.10
HGNCiHGNC:2019 CLCN1
MIMi118425 gene
neXtProtiNX_P35523

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 118CytoplasmicCuratedAdd BLAST118
Transmembranei119 – 150Helical1 PublicationAdd BLAST32
Topological domaini151 – 158ExtracellularCurated8
Transmembranei159 – 179Helical1 PublicationAdd BLAST21
Topological domaini180 – 183CytoplasmicCurated4
Intramembranei184 – 195Helical1 PublicationAdd BLAST12
Topological domaini196 – 208CytoplasmicCuratedAdd BLAST13
Transmembranei209 – 228Helical1 PublicationAdd BLAST20
Transmembranei229 – 246Helical1 PublicationAdd BLAST18
Topological domaini247 – 268CytoplasmicCuratedAdd BLAST22
Intramembranei269 – 290Helical1 PublicationAdd BLAST22
Topological domaini291 – 301CytoplasmicCuratedAdd BLAST11
Transmembranei302 – 321Helical1 PublicationAdd BLAST20
Topological domaini322 – 347ExtracellularCuratedAdd BLAST26
Transmembranei348 – 376Helical1 PublicationAdd BLAST29
Topological domaini377 – 390CytoplasmicCuratedAdd BLAST14
Transmembranei391 – 408Helical1 PublicationAdd BLAST18
Topological domaini409 – 414ExtracellularCurated6
Intramembranei415 – 426Helical1 PublicationAdd BLAST12
Topological domaini427 – 457ExtracellularCuratedAdd BLAST31
Transmembranei458 – 478Helical1 PublicationAdd BLAST21
Transmembranei479 – 498Helical1 PublicationAdd BLAST20
Topological domaini499 – 521ExtracellularCuratedAdd BLAST23
Intramembranei522 – 554Helical1 PublicationAdd BLAST33
Topological domaini555 – 557ExtracellularCurated3
Transmembranei558 – 578Helical1 PublicationAdd BLAST21
Topological domaini579 – 988CytoplasmicCuratedAdd BLAST410

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Myotonia congenita, autosomal dominant (MCAD)12 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 dbSNP:rs80356699EnsemblClinVar.1
Natural variantiVAR_075597193E → K in MCAD. 1 PublicationCorresponds to variant dbSNP:rs80356686EnsemblClinVar.1
Natural variantiVAR_075599198L → P in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel. 1 Publication1
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 dbSNP:rs80356689EnsemblClinVar.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 dbSNP:rs80356690EnsemblClinVar.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 dbSNP:rs80356701EnsemblClinVar.1
Natural variantiVAR_001600317R → Q in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel. 2 PublicationsCorresponds to variant dbSNP:rs80356702EnsemblClinVar.1
Natural variantiVAR_077244480P → H in MCAD; decreased protein abundance. 1 Publication1
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 dbSNP:rs80356694EnsemblClinVar.1
Natural variantiVAR_075605484F → L in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect. 1 PublicationCorresponds to variant dbSNP:rs1312002847Ensembl.1
Natural variantiVAR_079520950E → K in MCAD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201506176Ensembl.1
Myotonia congenita, autosomal recessive (MCAR)20 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 dbSNP:rs769312894Ensembl.1
Natural variantiVAR_07559082T → A in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant dbSNP:rs772100356Ensembl.1
Natural variantiVAR_001582105R → C in MCAR; no effect on chloride transport. 1 PublicationCorresponds to variant dbSNP:rs201509501Ensembl.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 dbSNP:rs748639603Ensembl.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 dbSNP:rs771532474Ensembl.1
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 dbSNP:rs149729531EnsemblClinVar.1
Natural variantiVAR_075596190G → S in MCAR; loss of chloride channel activity. 3 PublicationsCorresponds to variant dbSNP:rs797045032EnsemblClinVar.1
Natural variantiVAR_075598197I → R in MCAR; changed chloride channel activity. 1 Publication1
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 dbSNP:rs200621976Ensembl.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 dbSNP:rs757109632Ensembl.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 dbSNP:rs150885084EnsemblClinVar.1
Natural variantiVAR_001596291E → K in MCAR; loss of calcium channel activity; no dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs121912805EnsemblClinVar.1
Natural variantiVAR_001601327V → I in MCAR. Corresponds to variant dbSNP:rs774396430EnsemblClinVar.1
Natural variantiVAR_001602329I → T in MCAR. 1
Natural variantiVAR_075603412Q → P in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded. 1 PublicationCorresponds to variant dbSNP:rs1279658001Ensembl.1
Natural variantiVAR_001604413F → C in MCAR. 1 PublicationCorresponds to variant dbSNP:rs121912799EnsemblClinVar.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 dbSNP:rs376026619EnsemblClinVar.1
Natural variantiVAR_001608482G → R in MCAR. Corresponds to variant dbSNP:rs746125212EnsemblClinVar.1
Natural variantiVAR_001609485M → V in MCAR. 1 PublicationCorresponds to variant dbSNP:rs146457619EnsemblClinVar.1
Natural variantiVAR_001610496R → S in MCAR; loss of chloride channel activity; recessive. 2 PublicationsCorresponds to variant dbSNP:rs121912801EnsemblClinVar.1
Natural variantiVAR_075606499G → R in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating. 1 PublicationCorresponds to variant dbSNP:rs121912807EnsemblClinVar.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_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 dbSNP:rs755433272Ensembl.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 dbSNP:rs80356706EnsemblClinVar.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
GeneReviewsiCLCN1
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
ProteomicsDBi55076

PTM databases

iPTMnetiP35523
PhosphoSitePlusiP35523

Expressioni

Tissue specificityi

Predominantly expressed in skeletal muscles.

Gene expression databases

BgeeiENSG00000188037 Expressed in 74 organ(s), highest expression level in muscle of leg
CleanExiHS_CLCN1
ExpressionAtlasiP35523 baseline and differential
GenevisibleiP35523 HS

Interactioni

Subunit structurei

Homodimer.1 Publication2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107594, 10 interactors
IntActiP35523, 4 interactors
STRINGi9606.ENSP00000339867

Chemistry databases

BindingDBiP35523

Structurei

Secondary structure

1988
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP35523
SMRiP35523
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

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.3080.10, 1 hit
InterProiView protein in InterPro
IPR000644 CBS_dom
IPR014743 Cl-channel_core
IPR001807 Cl-channel_volt-gated
IPR002243 Cl_channel-1
PfamiView protein in Pfam
PF00654 Voltage_CLC, 1 hit
PRINTSiPR00762 CLCHANNEL
PR01112 CLCHANNEL1
SUPFAMiSSF81340 SSF81340, 1 hit
PROSITEiView protein in PROSITE
PS51371 CBS, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C0N6H7C0N6_HUMAN
Chloride channel protein 1
CLCN1
76Annotation score:
H7C1F4H7C1F4_HUMAN
Chloride channel protein 1
CLCN1
102Annotation score:

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 dbSNP:rs769312894Ensembl.1
Natural variantiVAR_07559082T → A in MCAR; unknown pathological significance; no effect on chloride transport. 1 PublicationCorresponds to variant dbSNP:rs772100356Ensembl.1
Natural variantiVAR_001582105R → C in MCAR; no effect on chloride transport. 1 PublicationCorresponds to variant dbSNP:rs201509501Ensembl.1
Natural variantiVAR_001583118G → W2 PublicationsCorresponds to variant dbSNP:rs10282312Ensembl.1
Natural variantiVAR_075591128M → V in MCAD. 1 PublicationCorresponds to variant dbSNP:rs80356699EnsemblClinVar.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 dbSNP:rs748639603Ensembl.1
Natural variantiVAR_001585150Y → C in MCAR. 1 Publication1
Natural variantiVAR_075593154Q → R Polymorphism; no effect on chloride transport. 1 PublicationCorresponds to variant dbSNP:rs111482384EnsemblClinVar.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 dbSNP:rs771532474Ensembl.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 dbSNP:rs149729531EnsemblClinVar.1
Natural variantiVAR_075596190G → S in MCAR; loss of chloride channel activity. 3 PublicationsCorresponds to variant dbSNP:rs797045032EnsemblClinVar.1
Natural variantiVAR_075597193E → K in MCAD. 1 PublicationCorresponds to variant dbSNP:rs80356686EnsemblClinVar.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 dbSNP:rs80356700EnsemblClinVar.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 dbSNP:rs200621976Ensembl.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 dbSNP:rs757109632Ensembl.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 dbSNP:rs150885084EnsemblClinVar.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 dbSNP:rs80356689EnsemblClinVar.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 dbSNP:rs80356690EnsemblClinVar.1
Natural variantiVAR_001596291E → K in MCAR; loss of calcium channel activity; no dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs121912805EnsemblClinVar.1
Natural variantiVAR_001597300R → Q Polymorphism; no effect on chloride transport. 2 PublicationsCorresponds to variant dbSNP:rs118066140EnsemblClinVar.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 dbSNP:rs80356701EnsemblClinVar.1
Natural variantiVAR_001599313A → T in MCAD and MCAR. 1 PublicationCorresponds to variant dbSNP:rs80356692EnsemblClinVar.1
Natural variantiVAR_001600317R → Q in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel. 2 PublicationsCorresponds to variant dbSNP:rs80356702EnsemblClinVar.1
Natural variantiVAR_001601327V → I in MCAR. Corresponds to variant dbSNP:rs774396430EnsemblClinVar.1
Natural variantiVAR_001602329I → T in MCAR. 1
Natural variantiVAR_001603338R → Q in MCAD and MCAR. 1 PublicationCorresponds to variant dbSNP:rs80356703EnsemblClinVar.1
Natural variantiVAR_075603412Q → P in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded. 1 PublicationCorresponds to variant dbSNP:rs1279658001Ensembl.1
Natural variantiVAR_001604413F → C in MCAR. 1 PublicationCorresponds to variant dbSNP:rs121912799EnsemblClinVar.1
Natural variantiVAR_001605415A → V in MCAR. 1 Publication1
Natural variantiVAR_001606437A → T Polymorphism. 1 PublicationCorresponds to variant dbSNP:rs41276054EnsemblClinVar.1
Natural variantiVAR_075604453R → W in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs376026619EnsemblClinVar.1
Natural variantiVAR_077244480P → H in MCAD; decreased protein abundance. 1 Publication1
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 dbSNP:rs80356694EnsemblClinVar.1
Natural variantiVAR_001608482G → R in MCAR. Corresponds to variant dbSNP:rs746125212EnsemblClinVar.1
Natural variantiVAR_075605484F → L in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect. 1 PublicationCorresponds to variant dbSNP:rs1312002847Ensembl.1
Natural variantiVAR_001609485M → V in MCAR. 1 PublicationCorresponds to variant dbSNP:rs146457619EnsemblClinVar.1
Natural variantiVAR_001610496R → S in MCAR; loss of chloride channel activity; recessive. 2 PublicationsCorresponds to variant dbSNP:rs121912801EnsemblClinVar.1
Natural variantiVAR_075606499G → R in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating. 1 PublicationCorresponds to variant dbSNP:rs121912807EnsemblClinVar.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 dbSNP:rs546411827Ensembl.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 dbSNP:rs80356696EnsemblClinVar.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 dbSNP:rs80356697EnsemblClinVar.1
Natural variantiVAR_001613563V → I in MCAR. 1 Publication1
Natural variantiVAR_075610614K → N Polymorphism. 1 PublicationCorresponds to variant dbSNP:rs140205115EnsemblClinVar.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 dbSNP:rs13438232EnsemblClinVar.1
Natural variantiVAR_075613845G → S in MCAR; unknown pathological significance; no effect on chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs755433272Ensembl.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 dbSNP:rs80356706EnsemblClinVar.1
Natural variantiVAR_075616947V → E in MCAR; unknown pathological significance. 1 Publication1
Natural variantiVAR_079520950E → K in MCAD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201506176Ensembl.1

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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6COYelectron microscopy3.36A/B1-988[»]
6COZelectron microscopy3.36A/B1-988[»]
ProteinModelPortaliP35523
SMRiP35523
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107594, 10 interactors
IntActiP35523, 4 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
ProteomicsDBi55076

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
EuPathDBiHostDB:ENSG00000188037.10
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
OMAiHISKYNI
OrthoDBiEOG091G01RJ
PhylomeDBiP35523
TreeFamiTF352264

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSiCLCN1 human
GeneWikiiCLCN1
GenomeRNAii1180
PROiPR:P35523
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188037 Expressed in 74 organ(s), highest expression level in muscle of leg
CleanExiHS_CLCN1
ExpressionAtlasiP35523 baseline and differential
GenevisibleiP35523 HS

Family and domain databases

Gene3Di1.10.3080.10, 1 hit
InterProiView protein in InterPro
IPR000644 CBS_dom
IPR014743 Cl-channel_core
IPR001807 Cl-channel_volt-gated
IPR002243 Cl_channel-1
PfamiView protein in Pfam
PF00654 Voltage_CLC, 1 hit
PRINTSiPR00762 CLCHANNEL
PR01112 CLCHANNEL1
SUPFAMiSSF81340 SSF81340, 1 hit
PROSITEiView protein in PROSITE
PS51371 CBS, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCLCN1_HUMAN
AccessioniPrimary (citable) accession number: P35523
Secondary accession number(s): A4D2H5, Q2M202
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 2, 2010
Last modified: November 7, 2018
This is version 182 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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