CLCN1
entrez
1180
canonical
uniprot
P35523
canonical
ensembl
ENSG00000188037
resolver
ensp
ENSP00000339867
resolver
enst
ENST00000343257
resolver
genesymbol
CLCN1
resolver
genesymbol_syn
CLC1
resolver
hgnc
HGNC:2019
resolver
uniprot
A4D2H5
resolver
uniprot
Q2M202
resolver
uniprot_entry
CLCN1_HUMAN
resolver
uniprot_sec
A4D2H5
resolver
uniprot_sec
Q2M202
resolver
activity_regulation
ACTIVITY REGULATION: Modulated by membrane voltage with depolarization favouring channel opening and hyperpolarization favouring channel closure. Inhibited by acidic pH and ATP binding due to a shift of voltage dependence of common gating to more positive voltages. Inhibited by 9-anthracene-carboxylic. {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:16027167, ECO:0000269|PubMed:31022181}.
uniprot
proteins
amino_acid_sequence
MEQSRSQQRGGEQSWWGSDPQYQYMPFEHCTSYGLPSENGGLQHRLRKDAGPRHNVHPTQIYGHHKEQFSDREQDIGMPKKTGSSSTVDSKDEDHYSKCQDCIHRLGQVVRRKLGEDGIFLVLLGLLMALVSWSMDYVSAKSLQAYKWSYAQMQPSLPLQFLVWVTFPLVLILFSALFCHLISPQAVGSGIPEMKTILRGVVLKEYLTMKAFVAKVVALTAGLGSGIPVGKEGPFVHIASICAAVLSKFMSVFCGVYEQPYYYSDILTVGCAVGVGCCFGTPLGGVLFSIEVTSTYFAVRNYWRGFFAATFSAFVFRVLAVWNKDAVTITALFRTNFRMDFPFDLKELPAFAAIGICCGLLGAVFVYLHRQVMLGVRKHKALSQFLAKHRLLYPGIVTFVIASFTFPPGMGQFMAGELMPREAISTLFDNNTWVKHAGDPESLGQSAVWIHPRVNVVIIIFLFFVMKFWMSIVATTMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPDGILFDDIIYKILPGGYAVIGAAALTGAVSHTVSTAVICFELTGQIAHILPMMVAVILANMVAQSLQPSLYDSIIQVKKLPYLPDLGWNQLSKYTIFVEDIMVRDVKFVSASYTYGELRTLLQTTTVKTLPLVDSKDSMILLGSVERSELQALLQRHLCPERRLRAAQEMARKLSELPYDGKARLAGEGLPGAPPGRPESFAFVDEDEDEDLSGKSELPPSLALHPSTTAPLSPEEPNGPLPGHKQQPEAPEPAGQRPSIFQSLLHCLLGRARPTKKKTTQDSTDLVDNMSPEEIEAWEQEQLSQPVCFDSCCIDQSPFQLVEQTTLHKTHTLFSLLGLHLAYVTSMGKLRGVLALEELQKAIEGHTKSGVQLRPPLASFRNTTSTRKSTGAPPSSAENWNLPEDRPGATGTGDVIAASPETPVPSPSPEPPLSLAPGKVEGELEELELVESPGLEEELADILQGPSLRSTDEEDEDELIL
uniprot
proteins
disease_involvement
DISEASE: Myotonia congenita, autosomal dominant (MCAD) [MIM:160800]: A 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). {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:10962018, ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:26096614, ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:27666773, ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:7981750, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8533761, ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myotonia congenita, autosomal recessive (MCAR) [MIM:255700]: A 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). {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:10215406, ECO:0000269|PubMed:10644771, ECO:0000269|PubMed:11113225, ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:1379744, ECO:0000269|PubMed:19697366, ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26096614, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7874130, ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:7981681, ECO:0000269|PubMed:8533761, ECO:0000269|PubMed:8571958, ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Voltage-gated chloride channel involved in skeletal muscle excitability. Generates most of the plasma membrane chloride conductance in skeletal muscle fibers, stabilizes the resting membrane potential and contributes to the repolarization phase during action potential firing (PubMed:12456816, PubMed:16027167, PubMed:22521272, PubMed:22641783, PubMed:26007199, PubMed:26502825, PubMed:26510092, PubMed:7951242, PubMed:8112288, PubMed:8130334, PubMed:9122265, PubMed:9565403, PubMed:9736777). Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Has a significant open probability at muscle resting potential and is further activated upon membrane depolarization (PubMed:10051520, PubMed:10962018, PubMed:29809153, PubMed:31022181). Permeable to small monovalent anions with ion selectivity for chloride > thiocyanate > bromide > nitrate > iodide (PubMed:9122265, PubMed:9565403). {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:10962018, ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:16027167, ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:29809153, ECO:0000269|PubMed:31022181, ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8130334, ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9565403, ECO:0000269|PubMed:9736777}.
uniprot
proteins
mass_dalton
108626
uniprot
proteins
mutagenesis
MUTAGEN 290; /note="I->C,E,F,G,K,L,Q,T,V,Y: Changed chloride channel activity; changed gating of the channel."; /evidence="ECO:0000269|PubMed:8845168"; MUTAGEN 291; /note="E->D: No effect on calcium channel activity."; /evidence="ECO:0000269|PubMed:8845168"; MUTAGEN 291; /note="E->L: Loss of calcium channel activity."; /evidence="ECO:0000269|PubMed:8845168"; MUTAGEN 496; /note="R->K: Changed gating of the channel."; /evidence="ECO:0000269|PubMed:10644771"; MUTAGEN 499; /note="G->K,E: Changed gating of the channel."; /evidence="ECO:0000269|PubMed:10644771"; MUTAGEN 499; /note="G->Q: No effect on gating of the channel."; /evidence="ECO:0000269|PubMed:10644771"; MUTAGEN 500; /note="E->Q: No effect on channel function."; /evidence="ECO:0000269|PubMed:10644771"; MUTAGEN 636; /note="T->A: Reduces the effect of adenosine nucleotides on common gate."; /evidence="ECO:0000269|PubMed:16027167"; MUTAGEN 638; /note="P->A: Reduces the effect of adenosine nucleotides on common gate."; /evidence="ECO:0000269|PubMed:16027167"; MUTAGEN 651; /note="S->A: Has normal sensitivity to adenosine nucleotides."; /evidence="ECO:0000269|PubMed:16027167"; MUTAGEN 847; /note="H->A: Reduces the effect of adenosine nucleotides on common gate."; /evidence="ECO:0000269|PubMed:16027167"; MUTAGEN 848; /note="L->A: Abrogates the effect of adenosine nucleotides on common gate."; /evidence="ECO:0000269|PubMed:16027167"; MUTAGEN 849; /note="A->V: Has normal sensitivity to adenosine nucleotides."; /evidence="ECO:0000269|PubMed:16027167
uniprot
proteins
protein_family
Chloride channel (TC 2.A.49) family
uniprot
proteins
protein_family
ClC-1/CLCN1 subfamily
uniprot
proteins
pubmed
10051520
uniprot
proteins
pubmed
10215406
uniprot
proteins
pubmed
10644771
uniprot
proteins
pubmed
10962018
uniprot
proteins
pubmed
11113225
uniprot
proteins
pubmed
12456816
uniprot
proteins
pubmed
12661046
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
1379744
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16027167
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
19697366
uniprot
proteins
pubmed
22521272
uniprot
proteins
pubmed
22641783
uniprot
proteins
pubmed
26007199
uniprot
proteins
pubmed
26096614
uniprot
proteins
pubmed
26502825
uniprot
proteins
pubmed
26510092
uniprot
proteins
pubmed
27653901
uniprot
proteins
pubmed
27666773
uniprot
proteins
pubmed
29809153
uniprot
proteins
pubmed
31022181
uniprot
proteins
pubmed
37892996
uniprot
proteins
pubmed
7581380
uniprot
proteins
pubmed
7874130
uniprot
proteins
pubmed
7951242
uniprot
proteins
pubmed
7981681
uniprot
proteins
pubmed
7981750
uniprot
proteins
pubmed
8112288
uniprot
proteins
pubmed
8130334
uniprot
proteins
pubmed
8533761
uniprot
proteins
pubmed
8571958
uniprot
proteins
pubmed
8845168
uniprot
proteins
pubmed
9122265
uniprot
proteins
pubmed
9565403
uniprot
proteins
pubmed
9566422
uniprot
proteins
pubmed
9736777
uniprot
proteins
sequence_length
988
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q64347}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma, T-tubule {ECO:0000250|UniProtKB:Q64347}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 119..150; /note="Helical"; /evidence="ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996, ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"; TRANSMEM 159..179; /note="Helical"; /evidence="ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996, ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"; TRANSMEM 302..321; /note="Helical"; /evidence="ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996, ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"; TRANSMEM 348..376; /note="Helical"; /evidence="ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996, ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"; TRANSMEM 391..408; /note="Helical"; /evidence="ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996, ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6
uniprot
proteins