CLCN2 (chloride voltage-gated channel 2)

Gene

• Entrez ID: 1181
• Gene name: Chloride voltage-gated channel 2
• Gene symbol: CLCN2
• Synonyms: CIC-2, CLC2, ECA2, ECA3, EGI11, EGI3, EGMA, EJM6, EJM8, FHA2, FHII, HALD2, LKPAT, clC-2
• Chromosome: 3
• Chromosome location: 3q27.1
• Summary: This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding diffe

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs71318369	C>T	Risk-factor, uncertain-significance	Intron variant, coding sequence variant, missense variant, non coding transcript variant
rs137852682	C>G,T	Risk-factor, uncertain-significance	Non coding transcript variant, missense variant, coding sequence variant
rs141242566	C>A,T	Pathogenic, uncertain-significance	Missense variant, non coding transcript variant, coding sequence variant
rs201330912	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs376823689	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, coding sequence variant, stop gained, intron variant
rs515726131	->C	Likely-pathogenic, uncertain-significance	Non coding transcript variant, coding sequence variant, frameshift variant, 5 prime UTR variant
rs532632165	C>G	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant
rs587777110	TGAGGA>-	Pathogenic	Upstream transcript variant, coding sequence variant, non coding transcript variant, inframe deletion, genic upstream transcript variant
rs587777111	G>A,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs587777112	->C	Pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, frameshift variant
rs758379595	A>G,T	Pathogenic	Genic upstream transcript variant, non coding transcript variant, missense variant, coding sequence variant, upstream transcript variant
rs771507094	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, intron variant, missense variant
rs777105668	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs863225249	C>G	Pathogenic	Intron variant, upstream transcript variant, non coding transcript variant, missense variant, coding sequence variant, genic upstream transcript variant
rs863225250	G>A,C	Pathogenic	Stop gained, non coding transcript variant, 5 prime UTR variant, missense variant, coding sequence variant
rs863225251	G>ATGAGCAGT	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant
rs863225252	A>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant
rs863225253	A>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs863225254	C>T	Pathogenic	Missense variant, intron variant, non coding transcript variant, coding sequence variant
rs863225255	AC>-	Pathogenic	Frameshift variant, intron variant, non coding transcript variant, coding sequence variant
rs863225256	T>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs1085307938	C>T	Pathogenic, likely-pathogenic	Missense variant, upstream transcript variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant
rs1293789661	C>T	Pathogenic	Upstream transcript variant, non coding transcript variant, coding sequence variant, missense variant, genic upstream transcript variant
rs1478304584	C>T	Pathogenic	Intron variant, splice acceptor variant, non coding transcript variant
rs1553855606	CACC>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, intron variant, coding sequence variant
rs1553856214	T>A	Pathogenic	5 prime UTR variant, non coding transcript variant, stop gained, coding sequence variant
rs1553857113	A>T	Pathogenic	Upstream transcript variant, non coding transcript variant, genic upstream transcript variant, missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017077	hsa-miR-335-5p	Microarray	18185580
MIRT052784	hsa-miR-1260b	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005247	Function	Voltage-gated chloride channel activity	IBA	21873635
GO:0005247	Function	Voltage-gated chloride channel activity	IDA	29403011
GO:0005886	Component	Plasma membrane	IDA	29403011
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0006821	Process	Chloride transport	IBA	21873635
GO:0032347	Process	Regulation of aldosterone biosynthetic process	IMP	29403011
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0034707	Component	Chloride channel complex	IEA
GO:0034765	Process	Regulation of ion transmembrane transport	IEA
GO:0060041	Process	Retina development in camera-type eye	IEA
GO:0060689	Process	Cell differentiation involved in salivary gland development	IEA
GO:1902476	Process	Chloride transmembrane transport	IEA

Other IDs

• MIM: 600570
• HGNC: 2020
• e!Ensembl: ENSG00000114859

Protein

• UniProt ID: P51788
• Protein name: Chloride channel protein 2 (ClC-2)
• Protein function: Voltage-gated and osmosensitive chloride channel. 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 s
• PDB: 7XF5, 7XJA, 8GQU, 8TA2, 8TA3, 8TA4, 8TA5, 8TA6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00654	Voltage_CLC	143 → 547	Voltage gated chloride channel	Family

• Sequence:

  MAAAAAEEGMEPRALQYEQTLMYGRYTQDLGAFAKEEAARIRLGGPEPWKGPPSSRAAPE
  LLEYGRSRCARCRVCSVRCHKFLVSRVGEDWIFLVLLGLLMALVSWVMDYAIAACLQAQQ
  WMSRGLNTSILLQYLAWVTYPVVLITFSAGFTQILAPQAVGSGIPEMKTILRGVVLKEYL
  TLKTFIAKVIGLTCALGSGMPLGKEGPFVHIASMCAALLSKFLSLFGGIYENESRNTEML
  AAACAVGVGCCFAAPIGGVLFSIEVTSTFFAVRNYWRGFFAATFSAFIFRVLAVWNRDEE
  TITALFKTRFRLDFPFDLQELPAFAVIGIASGFGGALFVYLNRKIVQVMRKQKTINRFLM
  RKRLLFPALVTLLISTLTFPPGFGQFMAGQLSQKETLVTLFDNRTWVRQGLVEELEPPST
  SQAWNPPRANVFLTLVIFILMKFWMSALATTIPVPCGAFMPVFVIGAAFGRLVGESMAAW
  FPDGIHTDSSTYRIVPGGYAVVGAAALAGAVTHTVSTAVIVFELTGQIAHILPVMIAVIL
  ANAVAQSLQPSLYDSIIRIKKLPYLPELGWGRHQQYRVRVEDIMVRDVPHVALSCTFRDL
  RLALHRTKGRMLALVESPESMILLGSIERSQVVALLGAQLSPARRRQHMQERRATQTSPL
  SDQEGPPTPEASVCFQVNTEDSAFPAARGETHKPLKPALKRGPSVTRNLGESPTGSAESA
  GIALRSLFCGSPPPEAASEKLESCEKRKLKRVRISLASDADLEGEMSPEEILEWEEQQLD
  EPVNFSDCKIDPAPFQLVERTSLHKTHTIFSLLGVDHAYVTSIGRLIGIVTLKELRKAIE
  GSVTAQGVKVRPPLASFRDSATSSSDTETTEVHALWGPHSRHGLPREGSPSDSDDKCQ

• Sequence length: 898

Pathways

KEGG:

Mineral absorption

Reactome:

Stimuli-sensing channels

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Epilepsy	Idiopathic generalized epilepsy	rs113994140, rs119454947, rs28937874, rs1589762127, rs104894166, rs28939075, rs2134001459, rs104894167, rs119488099, rs119488100, rs1805032, rs387906420, rs121917752, rs121918622, rs121434579, rs1581220270, rs281865564, rs387907313, rs397514564, rs397514670, rs768241563, rs587776973, rs587776974, rs587776975, rs879255234, rs587776976, rs587776977, rs121917993, rs398123588, rs13306758, rs587777363, rs587777364, rs587777458, rs587777459, rs541024038, rs797044545, rs730882240, rs786205703, rs794726859, rs796053126, rs796053035, rs796053216, rs796052839, rs869025201, rs797044999, rs797044998, rs797045045, rs794726762, rs869312971, rs869312972, rs879255652, rs886037938, rs886037958, rs886037959, rs886037960, rs886037961, rs886037962, rs886037965, rs886037966, rs886039245, rs886039246, rs886039251, rs886039252, rs772872014, rs886039253, rs886039256, rs757511744, rs886039261, rs886039263, rs578185749, rs886039266, rs886039268, rs886039269, rs886039273, rs368820286, rs1057518801, rs1057518688, rs1057519107, rs1057519273, rs752753379, rs767795673, rs1057519424, rs755946598, rs760609867, rs1057521066, rs1057524233, rs1060501488, rs1060501487, rs755127868, rs751533302, rs771373457, rs1475605360, rs1555401942, rs1553567864, rs200661329, rs766667249, rs1556607762, rs1555882921, rs1555882867, rs1555900914, rs1553546836, rs77216276, rs755595256, rs1554169267, rs747661902, rs2105890565, rs1021001959, rs1555441032, rs1555439541, rs1556526609, rs1315483224, rs759952667, rs1555885023, rs1553456695, rs1555942720, rs1569083500, rs1559127505, rs1206309859, rs1567139896, rs1567134495, rs1431914212, rs1569166925, rs1569255443, rs1568955379, rs1567152003, rs374158137, rs1567129567, rs1569523728, rs1568991466, rs1569186093, rs1569254004, rs1372605067, rs1569067939, rs1568963062, rs1563959514, rs1569012755, rs1559118914, rs1602338615, rs1596522356, rs1364913665, rs1596522300, rs1596526976, rs1229740428, rs1596385588, rs1596500172, rs1596505517, rs1601925213, rs1601970168, rs1602010382, rs1602903591, rs1603014297, rs1603014708, rs1601875057, rs1601970824, rs1601755632, rs1587393982, rs1592977444, rs1575562076, rs1570998206, rs1588057922, rs1596528731, rs1602349641, rs1587401875, rs2065899210, rs1596526915, rs2093486364, rs2056165149, rs2056100951, rs781482552, rs1899868619, rs1900088045, rs1898675878, rs1898686157, rs1898837245, rs1898844513, rs2082841677, rs2085727988, rs2092933941, rs2091657024, rs1899864955, rs1898844907, rs2083056830, rs2084070588, rs1899713412, rs2082695884, rs1977106116, rs1977105425, rs1443687532
Febrile seizures	Febrile Convulsions	rs121909761, rs121909672, rs121909673, rs121909674, rs1561645243, rs267606837, rs796052510, rs1553553485, rs1554097890, rs1554101202, rs1554098226, rs765574676, rs1045493304
Glioma	Glioma, mixed gliomas, Malignant Glioma	rs121909219, rs121909224, rs587776667, rs587776671, rs121909239, rs121909241, rs28933368, rs121913500, rs55863639, rs786201995, rs786202517, rs786201044, rs398123317, rs1057518425, rs121913499, rs1060500122, rs781647403, rs1060500126, rs1554897889, rs1114167629, rs1114167656, rs587782603, rs1554893824, rs1554900615, rs1564568660, rs786204900, rs762518389, rs1339631701	12843258
Hyperaldosteronism	Hyperaldosteronism, Hyperaldosteronism, Familial, Type II	rs28934586, rs104894068, rs387906778, rs386352319, rs587777437, rs587777438, rs587777439, rs786205050, rs771507094, rs1085307938, rs1553853557, rs1553856214, rs1293789661, rs1553857113, rs758379595	29403012, 29403012, 29403011
Hypertension	Hypertensive disease	rs13306026, rs13333226
Leukoencephalopathy	Leukoencephalopathy	rs34757931
Leukoencephalopathy with mild cerebellar ataxia and white matter edema	Leukoencephalopathy with mild cerebellar ataxia and white matter edema	rs201330912, rs587777110, rs587777111, rs587777112, rs376823689, rs771507094, rs863225252, rs863225251, rs863225250, rs1478304584
Myoclonic epilepsy	Juvenile Myoclonic Epilepsy	rs267607103, rs267607104, rs137852778, rs137852781, rs147484110, rs74315442, rs74315443, rs121909346, rs121918622, rs121918623, rs121917954, rs121917955, rs1574272192, rs121918624, rs121918625, rs121918628, rs121918629, rs121918630, rs1574061044, rs121918632, rs397514458, rs397514459, rs386833439, rs386833440, rs386833441, rs796943858, rs386833443, rs398122387, rs121917923, rs121917957, rs121917929, rs121917927, rs121917966, rs121917967, rs121917990, rs121917941, rs121917964, rs121917943, rs121917972, rs121917965, rs121917918, rs121917963, rs121917911, rs121917912, rs121917986, rs121917987, rs121917913, rs121917974, rs121917945, rs121917975, rs121917919, rs121917993, rs121917915, rs121917995, rs121917976, rs121917949, rs121917926, rs121917950, rs121917951, rs121917952, rs121917980, rs121917921, rs121917981, rs121917935, rs121917936, rs121917984, rs121917937, rs121917985, rs121917909, rs121917938, rs121917928, rs121918753, rs121918782, rs121918784, rs121918733, rs121918734, rs121918788, rs121918736, rs121917969, rs121918775, rs121918737, rs121918786, rs121918796, rs121918754, rs121918745, rs121918738, rs121918746, rs121918740, rs121918741, rs121918789, rs121918742, rs121918791, rs121918811, rs121917922, rs121918797, rs121918744, rs121918778, rs121918767, rs121918779, rs121918770, rs121918763, rs121918757, rs121918751, rs121918783, rs121918773, rs121918793, rs121918780, rs121918735, rs398123585, rs398123588, rs398123593, rs545986367, rs727504136, rs794726737, rs794726739, rs794726845, rs779614747, rs794726726, rs372098964, rs794726801, rs794726769, rs794726781, rs794726780, rs794726741, rs794726783, rs794726832, rs794726814, rs794726722, rs794726703, rs794726702, rs794726763, rs794726802, rs794726804, rs794726748, rs794726851, rs794726740, rs794726754, rs794726698, rs794726758, rs794726760, rs794726819, rs794726839, rs794726759, rs199727342, rs794726701, rs794726850, rs794726785, rs794726800, rs764037830, rs794726757, rs794726752, rs794726825, rs794726835, rs139300715, rs794726809, rs794726696, rs794726734, rs794726699, rs794726705, rs794726784, rs794726745, rs794726707, rs794726779, rs794726821, rs794726822, rs794726789, rs794726723, rs146878122, rs794726816, rs794726700, rs794726853, rs794726731, rs794726852, rs794726841, rs794726709, rs777939538, rs794726817, rs794726727, rs794726706, rs794726770, rs794726735, rs794726744, rs794726854, rs794726710, rs794726720, rs794726836, rs794726774, rs794726729, rs794726728, rs794726733, rs542420576, rs794726756, rs794726813, rs794726830, rs794726714, rs794726772, rs1696406839, rs794726842, rs794726828, rs794726823, rs794726708, rs794726808, rs794726716, rs121917971, rs794726718, rs794726721, rs794726761, rs794726815, rs794726786, rs794726787, rs794726697, rs794726775, rs794726712, rs794726794, rs794726738, rs794726805, rs767045134, rs794726820, rs794726766, rs794726750, rs794726743, rs794726742, rs794726795, rs794726730, rs794726806, rs794726747, rs794726838, rs794726778, rs794726834, rs794726736, rs794726704, rs794726773, rs794726749, rs794726717, rs794726790, rs794726829, rs794726807, rs794726810, rs121917989, rs794726826, rs794726725, rs794726818, rs794726776, rs794726777, rs794726765, rs794726753, rs794726732, rs794726799, rs794726695, rs794726792, rs794726767, rs794726768, rs794726844, rs794726782, rs794726797, rs794726843, rs794726798, rs794726824, rs794726837, rs794726846, rs794726788, rs794726847, rs794726812, rs794726771, rs794726751, rs773407463, rs794726755, rs794726719, rs794726724, rs794726833, rs794726827, rs1553551314, rs794726840, rs794726849, rs794726764, rs794726803, rs794726831, rs794726711, rs794726793, rs760361423, rs794726796, rs794726762, rs35595680, rs764444350, rs794726848, rs786205214, rs794729200, rs794729207, rs796053029, rs796053014, rs796053010, rs796053004, rs796053001, rs796052973, rs779184118, rs781746113, rs796052961, rs796052957, rs863225037, rs863225036, rs863225035, rs863225034, rs863225033, rs863225032, rs863225030, rs863225038, rs863225031, rs869312670, rs869312684, rs886039430, rs121917959, rs886041980, rs886042528, rs781507889, rs1057517959, rs1057518671, rs1057519533, rs1057519534, rs1057519530, rs1057519531, rs1060502189, rs1064794766, rs748759187, rs368609628, rs1553345874, rs121918795, rs1266877537, rs1553266166, rs1553522321, rs1553543215, rs1553525325, rs1553520530, rs1553544470, rs1553551493, rs1553553462, rs1553560831, rs201966711, rs537026414, rs1559101839, rs1559114303, rs1559149128, rs1553553527, rs1569006250, rs781657502, rs1574370981, rs1366966423, rs1574312497, rs796053036, rs1573949198, rs1573953706, rs1573963975, rs1573973548, rs1573984110, rs1574005699, rs1574007140, rs1574052179, rs1574069132, rs1574166948, rs1574168611, rs1574183148, rs886041292, rs1574208760, rs1574209023, rs1574217232, rs1553545567, rs796053094, rs1574240716, rs1553549471, rs1574264920, rs1574266816, rs1574271602, rs1574271644, rs1574291210, rs1574371141, rs1574371902, rs796052488, rs1581220163, rs1196223064, rs1574182550, rs1573953030, rs1574201555, rs1581829739, rs1574281711, rs1696401617, rs1692166604, rs1574006637, rs1689139851, rs1689186812, rs1689309551, rs1689680658, rs1697997770, rs1698732089, rs1698941202, rs1697667767, rs1691073965, rs1698009615	23756480, 19191339, 12612585

Unknown
Disease name	Disease term	dbSNP ID	References
Conn syndrome	Conn Syndrome		29403012
Glucocortocoid-insensitive hyperaldosteronism	Glucocortocoid-insensitive primary hyperaldosteronism
Leukoencephalopathy with ataxia	LEUKOENCEPHALOPATHY WITH ATAXIA		23707145, 12612585, 25745790, 19191339, 19710712, 24357685, 21703448, 25128180, 25655951
Metabolic alkalosis	Metabolic alkalosis
Mouth abnormalities	Mouth Abnormalities
Photosensitive tonic-clonic seizures	Photosensitive tonic-clonic seizures
Status epilepticus	Status Epilepticus