CLCN1_HUMAN
ID CLCN1_HUMAN Reviewed; 988 AA.
AC P35523; A4D2H5; Q2M202;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Chloride channel protein 1;
DE Short=ClC-1;
DE AltName: Full=Chloride channel protein, skeletal muscle;
GN Name=CLCN1 {ECO:0000312|HGNC:HGNC:2019}; Synonyms=CLC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT MCAD LEU-480, VARIANT
RP GLN-300, CHARACTERIZATION OF VARIANTS MCAD GLU-230 AND LEU-480,
RP CHARACTERIZATION OF VARIANT GLN-300, FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RX PubMed=8112288; DOI=10.1002/j.1460-2075.1994.tb06315.x;
RA Steinmeyer K., Lorenz C., Pusch M., Koch M.C., Jentsch T.J.;
RT "Multimeric structure of ClC-1 chloride channel revealed by mutations in
RT dominant myotonia congenita (Thomsen).";
RL EMBO J. 13:737-743(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-118.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 171-988, AND VARIANT MCAR CYS-413.
RX PubMed=1379744; DOI=10.1126/science.1379744;
RA Koch M.C., Steinmeyer K., Lorenz C., Ricker K., Wolf F., Otto M., Zoll B.,
RA Lehmann-Horn F., Grzeschik K.-H., Jentsch T.J.;
RT "The skeletal muscle chloride channel in dominant and recessive human
RT myotonia.";
RL Science 257:797-800(1992).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT MCAD GLU-230.
RX PubMed=7981750; DOI=10.1038/ng0493-305;
RA George A.L. Jr., Crackower M.A., Abdalla J.A., Hudson A.J., Ebers G.C.;
RT "Molecular basis of Thomsen's disease (autosomal dominant myotonia
RT congenita).";
RL Nat. Genet. 3:305-310(1993).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT MCAD
RP GLU-230.
RX PubMed=9122265; DOI=10.1073/pnas.94.6.2729;
RA Fahlke C., Beck C.L., George A.L. Jr.;
RT "A mutation in autosomal dominant myotonia congenita affects pore
RT properties of the muscle chloride channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2729-2734(1997).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT MYOTONIA
RP LEVIOR ARG-552.
RX PubMed=12456816; DOI=10.1113/jphysiol.2002.027037;
RA Ryan A., Ruedel R., Kuchenbecker M., Fahlke C.;
RT "A novel alteration of muscle chloride channel gating in myotonia levior.";
RL J. Physiol. (Lond.) 545:345-354(2002).
RN [8] {ECO:0007744|PDB:6COY, ECO:0007744|PDB:6COZ}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.36 ANGSTROMS), SUBUNIT, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND CATALYTIC ACTIVITY.
RX PubMed=29809153; DOI=10.7554/elife.36629;
RA Park E., MacKinnon R.;
RT "Structure of the CLC-1 chloride channel from Homo sapiens.";
RL Elife 7:0-0(2018).
RN [9]
RP VARIANT MCAR SER-496, CHARACTERIZATION OF VARIANT MCAR SER-496, AND
RP FUNCTION.
RX PubMed=7951242; DOI=10.1093/hmg/3.6.941;
RA Lorenz C., Meyer-Kleine C., Steinmeyer K., Koch M.C., Jentsch T.J.;
RT "Genomic organization of the human muscle chloride channel ClC-1 and
RT analysis of novel mutations leading to Becker-type myotonia.";
RL Hum. Mol. Genet. 3:941-946(1994).
RN [10]
RP VARIANT MCAR GLY-136.
RX PubMed=7981681; DOI=10.1093/hmg/3.7.1123;
RA Heine R., George A.L. Jr., Pika U., Deymeer F., Ruedel R., Lehmann-Horn F.;
RT "Proof of a non-functional muscle chloride channel in recessive myotonia
RT congenita (Becker) by detection of a 4 base pair deletion.";
RL Hum. Mol. Genet. 3:1123-1128(1994).
RN [11]
RP VARIANTS MCAR LEU-167 AND GLN-338, AND VARIANT GLN-300.
RX PubMed=7874130;
RA George A.L. Jr., Sloan-Brown K., Fenichel G.M., Mitchell G.A., Spiegel R.,
RA Pascuzzi R.M.;
RT "Nonsense and missense mutations of the muscle chloride channel gene in
RT patients with myotonia congenita.";
RL Hum. Mol. Genet. 3:2071-2072(1994).
RN [12]
RP VARIANTS MCAR AND MCAD.
RX PubMed=8533761;
RA Meyer-Kleine C., Steinmeyer K., Ricker K., Jentsch T.J., Koch M.C.;
RT "Spectrum of mutations in the major human skeletal muscle chloride channel
RT gene (CLCN1) leading to myotonia.";
RL Am. J. Hum. Genet. 57:1325-1334(1995).
RN [13]
RP VARIANT MCAD MET-290, VARIANT MYOTONIA LEVIOR ARG-552, AND VARIANT TRP-118.
RX PubMed=7581380; DOI=10.1093/hmg/4.8.1397;
RA Lehmann-Horn F., Mailaender V., Heine R., George A.L. Jr.;
RT "Myotonia levior is a chloride channel disorder.";
RL Hum. Mol. Genet. 4:1397-1402(1995).
RN [14]
RP VARIANT MCAD MET-290, VARIANT MCAR LYS-291, CHARACTERIZATION OF VARIANTS
RP MCAD MET-290; GLN-317 AND LEU-480, CHARACTERIZATION OF VARIANT MCAR
RP LYS-291, CHARACTERIZATION OF VARIANT MYOTONIA LEVIOR ARG-552, AND
RP MUTAGENESIS OF ILE-290 AND GLU-291.
RX PubMed=8845168; DOI=10.1016/0896-6273(95)90023-3;
RA Pusch M., Steinmeyer K., Koch M.C., Jentsch T.J.;
RT "Mutations in dominant human myotonia congenita drastically alter the
RT voltage dependence of the CIC-1 chloride channel.";
RL Neuron 15:1455-1463(1995).
RN [15]
RP VARIANTS MCAR CYS-150; ARG-200; CYS-261 AND VAL-415.
RX PubMed=8571958;
RA Mailaender V., Heine R., Deymeer F., Lehmann-Horn F.;
RT "Novel muscle chloride channel mutations and their effects on heterozygous
RT carriers.";
RL Am. J. Hum. Genet. 58:317-324(1996).
RN [16]
RP VARIANTS MCAD/MCAR LEU-236; GLU-285; ALA-286; SER-307; VAL-485 AND ASN-556,
RP CHARACTERIZATION OF VARIANTS MCAD/MCAR LEU-236; GLU-285; ALA-286; SER-307
RP AND ASN-556, AND FUNCTION.
RX PubMed=9736777; DOI=10.1093/hmg/7.11.1753;
RA Kubisch C., Schmidt-Rose T., Fontaine B., Bretag A.H., Jentsch T.J.;
RT "ClC-1 chloride channel mutations in myotonia congenita: variable
RT penetrance of mutations shifting the voltage dependence.";
RL Hum. Mol. Genet. 7:1753-1760(1998).
RN [17]
RP VARIANTS MCAR ILE-563 AND LEU-708.
RX PubMed=10215406;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<331::aid-humu13>3.0.co;2-0;
RA Sangiuolo F., Botta A., Mesoraca A., Servidei S., Merlini L., Fratta G.,
RA Novelli G., Dallapiccola B.;
RT "Identification of five new mutations and three novel polymorphisms in the
RT muscle chloride channel gene (CLCN1) in 20 Italian patients with dominant
RT and recessive myotonia congenita.";
RL Hum. Mutat. 11:331-331(1998).
RN [18]
RP VARIANTS MCAD/MCAR VAL-161; THR-313 AND ASN-556.
RX PubMed=9566422; DOI=10.1212/wnl.50.4.1176;
RA Plassart-Schiess E., Gervais A., Eymard B., Lagueny A., Pouget J.,
RA Warter J.-M., Fardeau M., Jentsch T.J., Fontaine B.;
RT "Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with
RT various modes of inheritance including incomplete dominance and
RT penetrance.";
RL Neurology 50:1176-1179(1998).
RN [19]
RP VARIANT MCAR ARG-499, CHARACTERIZATION OF VARIANT MCAR ARG-499, AND
RP MUTAGENESIS OF ARG-496; GLY-499 AND GLU-500.
RX PubMed=10644771; DOI=10.1074/jbc.275.4.2999;
RA Zhang J., Sanguinetti M.C., Kwiecinski H., Ptacek L.J.;
RT "Mechanism of inverted activation of ClC-1 channels caused by a novel
RT myotonia congenita mutation.";
RL J. Biol. Chem. 275:2999-3005(2000).
RN [20]
RP VARIANT MCAR LEU-932.
RX PubMed=11113225; DOI=10.1212/wnl.55.11.1697;
RA Nagamitsu S., Matsuura T., Khajavi M., Armstrong R., Gooch C., Harati Y.,
RA Ashizawa T.;
RT "A 'dystrophic' variant of autosomal recessive myotonia congenita caused by
RT novel mutations in the CLCN1 gene.";
RL Neurology 55:1697-1703(2000).
RN [21]
RP VARIANTS MCAD VAL-128; LYS-193; SER-307 AND LEU-480, VARIANT MCAR GLU-285,
RP AND VARIANTS THR-437 AND ASN-614.
RX PubMed=12661046; DOI=10.1002/mus.10347;
RA Colding-Joergensen E., DunOe M., Schwartz M., Vissing J.;
RT "Decrement of compound muscle action potential is related to mutation type
RT in myotonia congenita.";
RL Muscle Nerve 27:449-455(2003).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-548.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP VARIANT MCAR SER-190.
RX PubMed=19697366; DOI=10.1002/mus.21525;
RA Shalata A., Furman H., Adir V., Adir N., Hujeirat Y., Shalev S.A.,
RA Borochowitz Z.U.;
RT "Myotonia congenita in a large consanguineous Arab family: insight into the
RT clinical spectrum of carriers and double heterozygotes of a novel mutation
RT in the chloride channel CLCN1 gene.";
RL Muscle Nerve 41:464-469(2010).
RN [24]
RP VARIANTS MCAR ARG-164; ARG-197; ILE-533; LEU-536; SER-845 AND GLU-947,
RP CHARACTERIZATION OF VARIANTS MCAR ARG-164; SER-190; ARG-197 AND SER-845,
RP AND FUNCTION.
RX PubMed=22521272; DOI=10.1016/j.jns.2012.03.024;
RA Ulzi G., Lecchi M., Sansone V., Redaelli E., Corti E., Saccomanno D.,
RA Pagliarani S., Corti S., Magri F., Raimondi M., D'Angelo G., Modoni A.,
RA Bresolin N., Meola G., Wanke E., Comi G.P., Lucchiari S.;
RT "Myotonia congenita: novel mutations in CLCN1 gene and functional
RT characterizations in Italian patients.";
RL J. Neurol. Sci. 318:65-71(2012).
RN [25]
RP VARIANTS MCAR LEU-167; ARG-277; TYR-277 AND THR-527, AND CHARACTERIZATION
RP OF VARIANTS MCAR ARG-277 AND TYR-277.
RX PubMed=22641783; DOI=10.1113/jphysiol.2012.232785;
RA Weinberger S., Wojciechowski D., Sternberg D., Lehmann-Horn F.,
RA Jurkat-Rott K., Becher T., Begemann B., Fahlke C., Fischer M.;
RT "Disease-causing mutations C277R and C277Y modify gating of human ClC-1
RT chloride channels in myotonia congenita.";
RL J. Physiol. (Lond.) 590:3449-3464(2012).
RN [26]
RP VARIANTS MCAD PRO-198 AND LEU-484, CHARACTERIZATION OF VARIANTS MCAD
RP PRO-198 AND LEU-484, VARIANTS MCAR PRO-628 AND GLY-640, AND
RP CHARACTERIZATION OF VARIANTS MCAR PRO-628 AND GLY-640.
RX PubMed=26096614; DOI=10.1113/jp270358;
RA Imbrici P., Maggi L., Mangiatordi G.F., Dinardo M.M., Altamura C.,
RA Brugnoni R., Alberga D., Pinter G.L., Ricci G., Siciliano G., Micheli R.,
RA Annicchiarico G., Lattanzi G., Nicolotti O., Morandi L., Bernasconi P.,
RA Desaphy J.F., Mantegazza R., Camerino D.C.;
RT "ClC-1 mutations in myotonia congenita patients: insights into molecular
RT gating mechanisms and genotype-phenotype correlation.";
RL J. Physiol. (Lond.) 593:4181-4199(2015).
RN [27]
RP VARIANTS MCAR ALA-82; SER-190; VAL-270 AND TRP-453, CHARACTERIZATION OF
RP VARIANTS MCAR ALA-82; SER-190; VAL-270 AND TRP-453, AND FUNCTION.
RX PubMed=26007199; DOI=10.1007/s12017-015-8356-8;
RA Portaro S., Altamura C., Licata N., Camerino G.M., Imbrici P., Musumeci O.,
RA Rodolico C., Conte Camerino D., Toscano A., Desaphy J.F.;
RT "Clinical, molecular, and functional characterization of CLCN1 mutations in
RT three families with recessive myotonia congenita.";
RL NeuroMolecular Med. 17:285-296(2015).
RN [28]
RP VARIANTS MCAR ARG-43; LEU-70; ASP-137; HIS-160; SER-496 AND GLU-855,
RP CHARACTERIZATION OF VARIANTS MCAR ARG-43; LEU-70; ASP-137 AND HIS-160,
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=26502825; DOI=10.1038/srep15382;
RA Ronstedt K., Sternberg D., Detro-Dassen S., Gramkow T., Begemann B.,
RA Becher T., Kilian P., Grieschat M., Machtens J.P., Schmalzing G.,
RA Fischer M., Fahlke C.;
RT "Impaired surface membrane insertion of homo- and heterodimeric human
RT muscle chloride channels carrying amino-terminal myotonia-causing
RT mutations.";
RL Sci. Rep. 5:15382-15382(2015).
RN [29]
RP VARIANTS MCAR CYS-105; LEU-167 AND PRO-412, VARIANT ARG-154,
RP CHARACTERIZATION OF VARIANTS MCAR CYS-105; LEU-167 AND PRO-412,
RP CHARACTERIZATION OF VARIANT ARG-154, AND FUNCTION.
RX PubMed=26510092; DOI=10.1002/humu.22916;
RA Vindas-Smith R., Fiore M., Vasquez M., Cuenca P., Del Valle G.,
RA Lagostena L., Gaitan-Penas H., Estevez R., Pusch M., Morales F.;
RT "Identification and functional characterization of CLCN1 mutations found in
RT nondystrophic myotonia patients.";
RL Hum. Mutat. 37:74-83(2016).
RN [30]
RP VARIANT MCAD LYS-950.
RX PubMed=27653901; DOI=10.1016/j.jns.2016.08.030;
RA Kato H., Kokunai Y., Dalle C., Kubota T., Madokoro Y., Yuasa H., Uchida Y.,
RA Ikeda T., Mochizuki H., Nicole S., Fontaine B., Takahashi M.P., Mitake S.;
RT "A case of non-dystrophic myotonia with concomitant mutations in the SCN4A
RT and CLCN1 genes.";
RL J. Neurol. Sci. 369:254-258(2016).
RN [31]
RP VARIANT MCAD HIS-480, AND CHARACTERIZATION OF VARIANT MCAD HIS-480.
RX PubMed=27666773; DOI=10.1016/j.nmd.2016.08.016;
RA Mori Y., Yamashita S., Kato M., Masuda T., Takamatsu K., Kumamoto T.,
RA Sasaki R., Ando Y.;
RT "Thomsen disease with ptosis and abnormal MR findings.";
RL Neuromuscul. Disord. 26:805-808(2016).
CC -!- FUNCTION: Voltage-gated chloride channel (PubMed:8112288,
CC PubMed:9122265, PubMed:12456816). Plays an important role in membrane
CC repolarization in skeletal muscle cells after muscle contraction. The
CC CLC channel family contains both chloride channels and proton-coupled
CC anion transporters that exchange chloride or another anion for protons
CC (Probable). The absence of conserved gating glutamate residues is
CC typical for family members that function as channels (Probable).
CC {ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:22521272,
CC ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26502825,
CC ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7951242,
CC ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265,
CC ECO:0000269|PubMed:9736777, ECO:0000305|PubMed:29809153}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in);
CC Xref=Rhea:RHEA:29567, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996;
CC Evidence={ECO:0000303|PubMed:29809153};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26502825,
CC ECO:0000269|PubMed:29809153, ECO:0000305|PubMed:8112288}.
CC -!- INTERACTION:
CC P35523; Q92624: APPBP2; NbExp=6; IntAct=EBI-10206780, EBI-743771;
CC P35523; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-10206780, EBI-7062247;
CC P35523; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-10206780, EBI-10175124;
CC P35523; Q9NQX1-2: PRDM5; NbExp=3; IntAct=EBI-10206780, EBI-12859340;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12456816,
CC ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:8112288,
CC ECO:0000269|PubMed:9122265}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29809153}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscles.
CC -!- DISEASE: Myotonia congenita, autosomal dominant (MCAD) [MIM:160800]: A
CC non-dystrophic skeletal muscle disorder characterized by muscle
CC stiffness and an inability of the muscle to relax after voluntary
CC contraction. Most patients have symptom onset in the legs, which later
CC progresses to the arms, neck, and facial muscles. Many patients show
CC marked hypertrophy of the lower limb muscles. The autosomal dominant
CC form (Thomsen disease) is less common and less severe than the
CC autosomal recessive one (Becker disease). A milder form of autosomal
CC dominant myotonia is characterized by isolated myotonia without muscle
CC weakness, hypotrophy, or hypertrophy (myotonia levior).
CC {ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:26096614,
CC ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:27666773,
CC ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:7981750,
CC ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8533761,
CC ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9122265,
CC ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myotonia congenita, autosomal recessive (MCAR) [MIM:255700]: A
CC non-dystrophic skeletal muscle disorder characterized by muscle
CC stiffness and an inability of the muscle to relax after voluntary
CC contraction. Most patients have symptom onset in the legs, which later
CC progresses to the arms, neck, and facial muscles. Many patients show
CC marked hypertrophy of the lower limb muscles. The autosomal recessive
CC form (Becker disease) is more severe than the autosomal dominant one
CC (Thomsen disease). {ECO:0000269|PubMed:10215406,
CC ECO:0000269|PubMed:10644771, ECO:0000269|PubMed:11113225,
CC ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:1379744,
CC ECO:0000269|PubMed:19697366, ECO:0000269|PubMed:22521272,
CC ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199,
CC ECO:0000269|PubMed:26096614, ECO:0000269|PubMed:26502825,
CC ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7874130,
CC ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:7981681,
CC ECO:0000269|PubMed:8533761, ECO:0000269|PubMed:8571958,
CC ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9566422,
CC ECO:0000269|PubMed:9736777}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 1/CLCN1 subfamily. {ECO:0000305}.
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DR EMBL; Z25587; CAA80996.1; -; Genomic_DNA.
DR EMBL; Z25884; CAA81103.1; -; mRNA.
DR EMBL; CH236959; EAL23786.1; -; Genomic_DNA.
DR EMBL; BC112156; AAI12157.1; -; mRNA.
DR EMBL; BC113495; AAI13496.1; -; mRNA.
DR EMBL; M97820; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L08261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L08262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L08263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L08264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L08265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z25753; CAB56792.1; -; Genomic_DNA.
DR EMBL; Z25754; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25755; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25756; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25757; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25758; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25759; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25760; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25761; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25762; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25763; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25764; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25765; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25766; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25767; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25752; CAB56792.1; JOINED; Genomic_DNA.
DR EMBL; Z25768; CAB56814.1; -; Genomic_DNA.
DR EMBL; Z25872; CAB56814.1; JOINED; Genomic_DNA.
DR CCDS; CCDS5881.1; -.
DR PIR; S37078; S37078.
DR RefSeq; NP_000074.2; NM_000083.2.
DR PDB; 6COY; EM; 3.36 A; A/B=1-988.
DR PDB; 6COZ; EM; 3.36 A; A/B=1-988.
DR PDB; 6QV6; EM; 3.63 A; A/B=1-988.
DR PDB; 6QVB; EM; 4.34 A; A/B=1-988.
DR PDB; 6QVC; EM; 4.00 A; A/B=1-988.
DR PDB; 6QVD; EM; 4.34 A; A/B=1-988.
DR PDB; 6QVU; EM; 4.20 A; A/B=1-988.
DR PDBsum; 6COY; -.
DR PDBsum; 6COZ; -.
DR PDBsum; 6QV6; -.
DR PDBsum; 6QVB; -.
DR PDBsum; 6QVC; -.
DR PDBsum; 6QVD; -.
DR PDBsum; 6QVU; -.
DR AlphaFoldDB; P35523; -.
DR SMR; P35523; -.
DR BioGRID; 107594; 13.
DR IntAct; P35523; 6.
DR MINT; P35523; -.
DR STRING; 9606.ENSP00000339867; -.
DR BindingDB; P35523; -.
DR TCDB; 2.A.49.2.1; the chloride carrier/channel (clc) family.
DR iPTMnet; P35523; -.
DR PhosphoSitePlus; P35523; -.
DR BioMuta; CLCN1; -.
DR DMDM; 311033468; -.
DR EPD; P35523; -.
DR jPOST; P35523; -.
DR PaxDb; P35523; -.
DR PeptideAtlas; P35523; -.
DR PRIDE; P35523; -.
DR ProteomicsDB; 55076; -.
DR Antibodypedia; 32627; 151 antibodies from 23 providers.
DR DNASU; 1180; -.
DR Ensembl; ENST00000343257.7; ENSP00000339867.2; ENSG00000188037.14.
DR GeneID; 1180; -.
DR KEGG; hsa:1180; -.
DR MANE-Select; ENST00000343257.7; ENSP00000339867.2; NM_000083.3; NP_000074.3.
DR UCSC; uc003wcr.2; human.
DR CTD; 1180; -.
DR DisGeNET; 1180; -.
DR GeneCards; CLCN1; -.
DR GeneReviews; CLCN1; -.
DR HGNC; HGNC:2019; CLCN1.
DR HPA; ENSG00000188037; Tissue enriched (skeletal).
DR MalaCards; CLCN1; -.
DR MIM; 118425; gene.
DR MIM; 160800; phenotype.
DR MIM; 255700; phenotype.
DR neXtProt; NX_P35523; -.
DR OpenTargets; ENSG00000188037; -.
DR Orphanet; 614; Thomsen and Becker disease.
DR PharmGKB; PA26546; -.
DR VEuPathDB; HostDB:ENSG00000188037; -.
DR eggNOG; KOG0476; Eukaryota.
DR GeneTree; ENSGT00940000157383; -.
DR HOGENOM; CLU_006904_0_1_1; -.
DR InParanoid; P35523; -.
DR OMA; FFANCTW; -.
DR OrthoDB; 1131873at2759; -.
DR PhylomeDB; P35523; -.
DR TreeFam; TF352264; -.
DR PathwayCommons; P35523; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; P35523; -.
DR BioGRID-ORCS; 1180; 12 hits in 1059 CRISPR screens.
DR ChiTaRS; CLCN1; human.
DR GeneWiki; CLCN1; -.
DR GenomeRNAi; 1180; -.
DR Pharos; P35523; Tbio.
DR PRO; PR:P35523; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P35523; protein.
DR Bgee; ENSG00000188037; Expressed in hindlimb stylopod muscle and 93 other tissues.
DR ExpressionAtlas; P35523; baseline and differential.
DR Genevisible; P35523; HS.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IMP:UniProtKB.
DR GO; GO:1902476; P:chloride transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR GO; GO:0006936; P:muscle contraction; IMP:UniProtKB.
DR GO; GO:0019227; P:neuronal action potential propagation; IEA:Ensembl.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR014743; Cl-channel_core.
DR InterPro; IPR001807; Cl-channel_volt-gated.
DR InterPro; IPR002243; Cl_channel-1.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01112; CLCHANNEL1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; CBS domain; Cell membrane; Chloride; Chloride channel;
KW Disease variant; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..988
FT /note="Chloride channel protein 1"
FT /id="PRO_0000094429"
FT TOPO_DOM 1..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 119..150
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 151..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 180..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 184..195
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 196..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 209..228
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TRANSMEM 229..246
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 247..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 269..290
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 291..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 302..321
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 322..347
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 348..376
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 377..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..408
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 409..414
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 415..426
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 427..457
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TRANSMEM 479..498
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 499..521
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 522..554
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 555..557
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29809153"
FT TOPO_DOM 579..988
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 609..668
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 821..876
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 65..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 880..988
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 188..192
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 230..234
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 482..486
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 883..904
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 189
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 484
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 578
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64347"
FT VARIANT 43
FT /note="Q -> R (in MCAR; decreased chloride transport;
FT decreased localization to the plasma membrane; dominant
FT negative effect on chloride transport and localization to
FT the plasma membrane; no significant effect on chloride
FT channel activity; no effect on homodimerization;
FT dbSNP:rs868831424)"
FT /evidence="ECO:0000269|PubMed:26502825"
FT /id="VAR_075588"
FT VARIANT 70
FT /note="S -> L (in MCAR; unknown pathological significance;
FT no effect on chloride transport; dbSNP:rs769312894)"
FT /evidence="ECO:0000269|PubMed:26502825"
FT /id="VAR_075589"
FT VARIANT 82
FT /note="T -> A (in MCAR; unknown pathological significance;
FT no effect on chloride transport; dbSNP:rs772100356)"
FT /evidence="ECO:0000269|PubMed:26007199"
FT /id="VAR_075590"
FT VARIANT 105
FT /note="R -> C (in MCAR; no effect on chloride transport;
FT dbSNP:rs201509501)"
FT /evidence="ECO:0000269|PubMed:26510092"
FT /id="VAR_001582"
FT VARIANT 118
FT /note="G -> W (in dbSNP:rs10282312)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7581380"
FT /id="VAR_001583"
FT VARIANT 128
FT /note="M -> V (in MCAD; dbSNP:rs80356699)"
FT /evidence="ECO:0000269|PubMed:12661046"
FT /id="VAR_075591"
FT VARIANT 136
FT /note="D -> G (in MCAR)"
FT /evidence="ECO:0000269|PubMed:7981681"
FT /id="VAR_001584"
FT VARIANT 137
FT /note="Y -> D (in MCAR; reduced chloride transport;
FT decreased localization to the plasma membrane; no
FT significant effect on chloride channel activity;
FT dbSNP:rs748639603)"
FT /evidence="ECO:0000269|PubMed:26502825"
FT /id="VAR_075592"
FT VARIANT 150
FT /note="Y -> C (in MCAR)"
FT /evidence="ECO:0000269|PubMed:8571958"
FT /id="VAR_001585"
FT VARIANT 154
FT /note="Q -> R (no effect on chloride transport;
FT dbSNP:rs111482384)"
FT /evidence="ECO:0000269|PubMed:26510092"
FT /id="VAR_075593"
FT VARIANT 160
FT /note="Q -> H (in MCAR; reduced chloride transport;
FT decreased localization to the plasma membrane; no
FT significant effect on chloride channel activity;
FT dbSNP:rs771532474)"
FT /evidence="ECO:0000269|PubMed:26502825"
FT /id="VAR_075594"
FT VARIANT 161
FT /note="F -> V (in MCAD and MCAR)"
FT /evidence="ECO:0000269|PubMed:9566422"
FT /id="VAR_001586"
FT VARIANT 164
FT /note="W -> R (in MCAR; altered chloride channel activity)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075595"
FT VARIANT 165
FT /note="V -> G (in MCAR; dbSNP:rs1586485438)"
FT /id="VAR_001587"
FT VARIANT 167
FT /note="F -> L (in MCAR; no effect on chloride transport;
FT dbSNP:rs149729531)"
FT /evidence="ECO:0000269|PubMed:22641783,
FT ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7874130"
FT /id="VAR_001588"
FT VARIANT 190
FT /note="G -> S (in MCAR; loss of chloride channel activity;
FT dbSNP:rs797045032)"
FT /evidence="ECO:0000269|PubMed:19697366,
FT ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:26007199"
FT /id="VAR_075596"
FT VARIANT 193
FT /note="E -> K (in MCAD; dbSNP:rs80356686)"
FT /evidence="ECO:0000269|PubMed:12661046"
FT /id="VAR_075597"
FT VARIANT 197
FT /note="I -> R (in MCAR; changed chloride channel activity)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075598"
FT VARIANT 198
FT /note="L -> P (in MCAD; reduced chloride transport; changed
FT calcium channel activity; changed gating of the channel;
FT dbSNP:rs1347382107)"
FT /evidence="ECO:0000269|PubMed:26096614"
FT /id="VAR_075599"
FT VARIANT 200
FT /note="G -> R (in MCAD and MCAR; dbSNP:rs1563074523)"
FT /evidence="ECO:0000269|PubMed:8571958"
FT /id="VAR_001589"
FT VARIANT 230
FT /note="G -> E (in MCAD and MCAR; changed ion selectivity;
FT loss of chloride transport; mild dominant effect;
FT dbSNP:rs80356700)"
FT /evidence="ECO:0000269|PubMed:7981750,
FT ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265"
FT /id="VAR_001590"
FT VARIANT 236
FT /note="V -> L (in MCAR; loss of chloride transport; changed
FT calcium channel activity; changed gating of the channel;
FT dbSNP:rs776173406)"
FT /evidence="ECO:0000269|PubMed:9736777"
FT /id="VAR_001591"
FT VARIANT 261
FT /note="Y -> C (in MCAR; dbSNP:rs200621976)"
FT /evidence="ECO:0000269|PubMed:8571958"
FT /id="VAR_001592"
FT VARIANT 270
FT /note="G -> V (in MCAR; decreased chloride channel
FT activity)"
FT /evidence="ECO:0000269|PubMed:26007199"
FT /id="VAR_075600"
FT VARIANT 277
FT /note="C -> R (in MCAR; reduced chloride transport; no
FT effect on protein abundance; dbSNP:rs757109632)"
FT /evidence="ECO:0000269|PubMed:22641783"
FT /id="VAR_075601"
FT VARIANT 277
FT /note="C -> Y (in MCAR; reduced chloride transport; changed
FT calcium channel activity; changed gating of the channel; no
FT effect on protein abundance)"
FT /evidence="ECO:0000269|PubMed:22641783"
FT /id="VAR_075602"
FT VARIANT 285
FT /note="G -> E (in MCAR; loss of chloride channel activity;
FT dbSNP:rs150885084)"
FT /evidence="ECO:0000269|PubMed:12661046,
FT ECO:0000269|PubMed:9736777"
FT /id="VAR_001593"
FT VARIANT 286
FT /note="V -> A (in MCAD; reduced chloride transport; changed
FT calcium channel activity; changed gating of the channel;
FT dominant negative effect; dbSNP:rs80356689)"
FT /evidence="ECO:0000269|PubMed:9736777"
FT /id="VAR_001594"
FT VARIANT 290
FT /note="I -> M (in MCAD; reduced chloride transport; changed
FT chloride channel activity; changed gating of the channel;
FT dominant negative effect; dbSNP:rs80356690)"
FT /evidence="ECO:0000269|PubMed:7581380,
FT ECO:0000269|PubMed:8845168"
FT /id="VAR_001595"
FT VARIANT 291
FT /note="E -> K (in MCAR; loss of calcium channel activity;
FT no dominant negative effect; dbSNP:rs121912805)"
FT /evidence="ECO:0000269|PubMed:8533761,
FT ECO:0000269|PubMed:8845168"
FT /id="VAR_001596"
FT VARIANT 300
FT /note="R -> Q (no effect on chloride transport;
FT dbSNP:rs118066140)"
FT /evidence="ECO:0000269|PubMed:7874130,
FT ECO:0000269|PubMed:8112288"
FT /id="VAR_001597"
FT VARIANT 307
FT /note="F -> S (in MCAD; reduced chloride transport; changed
FT chloride channel activity; changed gating of the channel;
FT dominant negative effect; dbSNP:rs80356701)"
FT /evidence="ECO:0000269|PubMed:12661046,
FT ECO:0000269|PubMed:9736777"
FT /id="VAR_001598"
FT VARIANT 313
FT /note="A -> T (in MCAD and MCAR; dbSNP:rs80356692)"
FT /evidence="ECO:0000269|PubMed:9566422"
FT /id="VAR_001599"
FT VARIANT 317
FT /note="R -> Q (in MCAD; reduced chloride transport; changed
FT chloride channel activity; changed gating of the channel;
FT dbSNP:rs80356702)"
FT /evidence="ECO:0000269|PubMed:8533761,
FT ECO:0000269|PubMed:8845168"
FT /id="VAR_001600"
FT VARIANT 327
FT /note="V -> I (in MCAR; dbSNP:rs774396430)"
FT /id="VAR_001601"
FT VARIANT 329
FT /note="I -> T (in MCAR)"
FT /id="VAR_001602"
FT VARIANT 338
FT /note="R -> Q (in MCAD and MCAR; dbSNP:rs80356703)"
FT /evidence="ECO:0000269|PubMed:7874130"
FT /id="VAR_001603"
FT VARIANT 412
FT /note="Q -> P (in MCAR; loss of chloride transport;
FT decreased localization to the plasma membrane; loss of
FT homodimerization; might be degraded; dbSNP:rs1279658001)"
FT /evidence="ECO:0000269|PubMed:26510092"
FT /id="VAR_075603"
FT VARIANT 413
FT /note="F -> C (in MCAR; dbSNP:rs121912799)"
FT /evidence="ECO:0000269|PubMed:1379744"
FT /id="VAR_001604"
FT VARIANT 415
FT /note="A -> V (in MCAR)"
FT /evidence="ECO:0000269|PubMed:8571958"
FT /id="VAR_001605"
FT VARIANT 437
FT /note="A -> T (in dbSNP:rs41276054)"
FT /evidence="ECO:0000269|PubMed:12661046"
FT /id="VAR_001606"
FT VARIANT 453
FT /note="R -> W (in MCAR; unknown pathological significance;
FT no effect on chloride channel activity; dbSNP:rs376026619)"
FT /evidence="ECO:0000269|PubMed:26007199"
FT /id="VAR_075604"
FT VARIANT 480
FT /note="P -> H (in MCAD; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:27666773"
FT /id="VAR_077244"
FT VARIANT 480
FT /note="P -> L (in MCAD; loss of chloride transport; changed
FT chloride channel activity; changed gating of the channel;
FT dominant effect; dbSNP:rs80356694)"
FT /evidence="ECO:0000269|PubMed:12661046,
FT ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8845168"
FT /id="VAR_001607"
FT VARIANT 482
FT /note="G -> R (in MCAR; dbSNP:rs746125212)"
FT /id="VAR_001608"
FT VARIANT 484
FT /note="F -> L (in MCAD; reduced chloride transport; changed
FT calcium channel activity; changed channel gating; no
FT dominant negative effect; dbSNP:rs1312002847)"
FT /evidence="ECO:0000269|PubMed:26096614"
FT /id="VAR_075605"
FT VARIANT 485
FT /note="M -> V (in MCAR; dbSNP:rs146457619)"
FT /evidence="ECO:0000269|PubMed:9736777"
FT /id="VAR_001609"
FT VARIANT 496
FT /note="R -> S (in MCAR; loss of chloride channel activity;
FT recessive; dbSNP:rs121912801)"
FT /evidence="ECO:0000269|PubMed:26502825,
FT ECO:0000269|PubMed:7951242"
FT /id="VAR_001610"
FT VARIANT 499
FT /note="G -> R (in MCAR; reduced chloride transport; changed
FT calcium channel activity; changed channel gating;
FT dbSNP:rs121912807)"
FT /evidence="ECO:0000269|PubMed:10644771"
FT /id="VAR_075606"
FT VARIANT 527
FT /note="I -> T (in MCAR; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22641783"
FT /id="VAR_075607"
FT VARIANT 533
FT /note="T -> I (in MCAR; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075608"
FT VARIANT 536
FT /note="V -> L (in MCAR; unknown pathological significance;
FT dbSNP:rs777685454)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075609"
FT VARIANT 548
FT /note="E -> K (in a breast cancer sample; somatic mutation;
FT dbSNP:rs546411827)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036300"
FT VARIANT 552
FT /note="Q -> R (in MCAD and MCAR; also found in myotonia
FT levior; reduced chloride transport; changed calcium channel
FT activity; changed channel gating; weak dominant negative
FT effect; dbSNP:rs80356696)"
FT /evidence="ECO:0000269|PubMed:12456816,
FT ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:8845168"
FT /id="VAR_001611"
FT VARIANT 556
FT /note="I -> N (in MCAD and MCAR; mild form; reduced
FT chloride transport; changed chloride channel activity;
FT changed gating of the channel; partial dominant negative
FT effect; dbSNP:rs80356697)"
FT /evidence="ECO:0000269|PubMed:9566422,
FT ECO:0000269|PubMed:9736777"
FT /id="VAR_001612"
FT VARIANT 563
FT /note="V -> I (in MCAR)"
FT /evidence="ECO:0000269|PubMed:10215406"
FT /id="VAR_001613"
FT VARIANT 614
FT /note="K -> N (in dbSNP:rs140205115)"
FT /evidence="ECO:0000269|PubMed:12661046"
FT /id="VAR_075610"
FT VARIANT 628
FT /note="L -> P (in MCAR; unknown pathological significance;
FT no effect on calcium channel activity)"
FT /evidence="ECO:0000269|PubMed:26096614"
FT /id="VAR_075611"
FT VARIANT 640
FT /note="V -> G (in MCAR; reduced calcium channel activity)"
FT /evidence="ECO:0000269|PubMed:26096614"
FT /id="VAR_075612"
FT VARIANT 708
FT /note="F -> L (in MCAR)"
FT /evidence="ECO:0000269|PubMed:10215406"
FT /id="VAR_001614"
FT VARIANT 727
FT /note="P -> L (in dbSNP:rs13438232)"
FT /id="VAR_047779"
FT VARIANT 845
FT /note="G -> S (in MCAR; unknown pathological significance;
FT no effect on chloride channel activity; dbSNP:rs755433272)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075613"
FT VARIANT 855
FT /note="G -> E (in MCAR; unknown pathological significance;
FT dbSNP:rs1554439879)"
FT /evidence="ECO:0000269|PubMed:26502825"
FT /id="VAR_075614"
FT VARIANT 932
FT /note="P -> L (in MCAR; unknown pathological significance;
FT dbSNP:rs80356706)"
FT /evidence="ECO:0000269|PubMed:11113225"
FT /id="VAR_075615"
FT VARIANT 947
FT /note="V -> E (in MCAR; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22521272"
FT /id="VAR_075616"
FT VARIANT 950
FT /note="E -> K (in MCAD; unknown pathological significance;
FT dbSNP:rs201506176)"
FT /evidence="ECO:0000269|PubMed:27653901"
FT /id="VAR_079520"
FT MUTAGEN 290
FT /note="I->C,E,F,G,K,L,Q,T,V,Y: Changed chloride channel
FT activity; changed gating of the channel."
FT /evidence="ECO:0000269|PubMed:8845168"
FT MUTAGEN 291
FT /note="E->D: No effect on calcium channel activity."
FT /evidence="ECO:0000269|PubMed:8845168"
FT MUTAGEN 291
FT /note="E->L: Loss of calcium channel activity."
FT /evidence="ECO:0000269|PubMed:8845168"
FT MUTAGEN 496
FT /note="R->K: Changed gating of the channel."
FT /evidence="ECO:0000269|PubMed:10644771"
FT MUTAGEN 499
FT /note="G->K,E: Changed gating of the channel."
FT /evidence="ECO:0000269|PubMed:10644771"
FT MUTAGEN 499
FT /note="G->Q: No effect on gating of the channel."
FT /evidence="ECO:0000269|PubMed:10644771"
FT MUTAGEN 500
FT /note="E->Q: No effect on channel function."
FT /evidence="ECO:0000269|PubMed:10644771"
FT CONFLICT 697
FT /note="L -> P (in Ref. 1; CAA80996/CAA81103)"
FT /evidence="ECO:0000305"
FT HELIX 117..151
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 152..155
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 157..182
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 191..198
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 209..223
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 232..249
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 263..279
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 293..298
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 299..322
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 348..378
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 382..388
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 392..405
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 407..410
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 414..417
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 420..427
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 440..449
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 456..474
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 477..480
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 484..502
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:6COY"
FT STRAND 515..517
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 522..537
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 542..550
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 556..570
FT /evidence="ECO:0007829|PDB:6COY"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 577..584
FT /evidence="ECO:0007829|PDB:6COY"
FT HELIX 605..608
FT /evidence="ECO:0007829|PDB:6COZ"
FT STRAND 609..611
FT /evidence="ECO:0007829|PDB:6COZ"
FT HELIX 622..631
FT /evidence="ECO:0007829|PDB:6COZ"
FT STRAND 635..641
FT /evidence="ECO:0007829|PDB:6COZ"
FT TURN 643..645
FT /evidence="ECO:0007829|PDB:6COZ"
FT STRAND 647..653
FT /evidence="ECO:0007829|PDB:6COZ"
FT HELIX 654..665
FT /evidence="ECO:0007829|PDB:6COZ"
FT HELIX 799..810
FT /evidence="ECO:0007829|PDB:6COZ"
FT HELIX 834..843
FT /evidence="ECO:0007829|PDB:6COZ"
FT STRAND 851..853
FT /evidence="ECO:0007829|PDB:6COZ"
FT STRAND 856..860
FT /evidence="ECO:0007829|PDB:6COZ"
FT HELIX 863..875
FT /evidence="ECO:0007829|PDB:6COZ"
SQ SEQUENCE 988 AA; 108626 MW; CA838BCD2AF3CA68 CRC64;
MEQSRSQQRG GEQSWWGSDP QYQYMPFEHC TSYGLPSENG GLQHRLRKDA GPRHNVHPTQ
IYGHHKEQFS DREQDIGMPK KTGSSSTVDS KDEDHYSKCQ DCIHRLGQVV RRKLGEDGIF
LVLLGLLMAL VSWSMDYVSA KSLQAYKWSY AQMQPSLPLQ FLVWVTFPLV LILFSALFCH
LISPQAVGSG IPEMKTILRG VVLKEYLTMK AFVAKVVALT AGLGSGIPVG KEGPFVHIAS
ICAAVLSKFM SVFCGVYEQP YYYSDILTVG CAVGVGCCFG TPLGGVLFSI EVTSTYFAVR
NYWRGFFAAT FSAFVFRVLA VWNKDAVTIT ALFRTNFRMD FPFDLKELPA FAAIGICCGL
LGAVFVYLHR QVMLGVRKHK ALSQFLAKHR LLYPGIVTFV IASFTFPPGM GQFMAGELMP
REAISTLFDN NTWVKHAGDP ESLGQSAVWI HPRVNVVIII FLFFVMKFWM SIVATTMPIP
CGGFMPVFVL GAAFGRLVGE IMAMLFPDGI LFDDIIYKIL PGGYAVIGAA ALTGAVSHTV
STAVICFELT GQIAHILPMM VAVILANMVA QSLQPSLYDS IIQVKKLPYL PDLGWNQLSK
YTIFVEDIMV RDVKFVSASY TYGELRTLLQ TTTVKTLPLV DSKDSMILLG SVERSELQAL
LQRHLCPERR LRAAQEMARK LSELPYDGKA RLAGEGLPGA PPGRPESFAF VDEDEDEDLS
GKSELPPSLA LHPSTTAPLS PEEPNGPLPG HKQQPEAPEP AGQRPSIFQS LLHCLLGRAR
PTKKKTTQDS TDLVDNMSPE EIEAWEQEQL SQPVCFDSCC IDQSPFQLVE QTTLHKTHTL
FSLLGLHLAY VTSMGKLRGV LALEELQKAI EGHTKSGVQL RPPLASFRNT TSTRKSTGAP
PSSAENWNLP EDRPGATGTG DVIAASPETP VPSPSPEPPL SLAPGKVEGE LEELELVESP
GLEEELADIL QGPSLRSTDE EDEDELIL
