Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	1181
Gene name	Chloride voltage-gated channel 2
Gene symbol	CLCN2
Synonyms (NCBI Gene)	CIC-2CLC2ECA2ECA3EGI11EGI3EGMAEJM6EJM8FHA2FHIIHALD2LKPATclC-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

Show/Hide all (27)

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

Show/Hide all (2)

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

Show/Hide all (50)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005247	Function	Voltage-gated chloride channel activity	IBA
GO:0005247	Function	Voltage-gated chloride channel activity	IDA	16155254, 29403011, 36964785
GO:0005247	Function	Voltage-gated chloride channel activity	IEA
GO:0005247	Function	Voltage-gated chloride channel activity	TAS	7795595
GO:0005254	Function	Chloride channel activity	IEA
GO:0005515	Function	Protein binding	IPI	26871637
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	29403011
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006821	Process	Chloride transport	IBA
GO:0006821	Process	Chloride transport	IEA
GO:0006911	Process	Phagocytosis, engulfment	IMP	36964785
GO:0008308	Function	Voltage-gated monoatomic anion channel activity	IEA
GO:0015108	Function	Chloride transmembrane transporter activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IDA	16155254
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0017081	Function	Chloride channel regulator activity	IMP	38345841
GO:0030322	Process	Stabilization of membrane potential	IEA
GO:0030324	Process	Lung development	IEA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0032347	Process	Regulation of aldosterone biosynthetic process	IMP	29403011
GO:0032591	Component	Dendritic spine membrane	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0034707	Component	Chloride channel complex	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043194	Component	Axon initial segment	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0043209	Component	Myelin sheath	IDA	22405205
GO:0043209	Component	Myelin sheath	IEA
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0048714	Process	Positive regulation of oligodendrocyte differentiation	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0060041	Process	Retina development in camera-type eye	IEA
GO:0060075	Process	Regulation of resting membrane potential	IEA
GO:0060689	Process	Cell differentiation involved in salivary gland development	IEA
GO:0065008	Process	Regulation of biological quality	IEA
GO:0071476	Process	Cellular hypotonic response	IEA
GO:0072320	Function	Volume-sensitive chloride channel activity	IEA
GO:0090425	Process	Acinar cell differentiation	IEA
GO:0097450	Component	Astrocyte end-foot	IDA	22405205
GO:0097450	Component	Astrocyte end-foot	IEA
GO:0098656	Process	Monoatomic anion transmembrane transport	IEA
GO:0098902	Process	Regulation of membrane depolarization during action potential	IEA
GO:1902476	Process	Chloride transmembrane transport	IEA

MIM	HGNC	e!Ensembl
600570	2020	ENSG00000114859

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

Tissue specificity

TISSUE SPECIFICITY: Ubiquitously expressed. Moderately expressed in aortic and coronary vascular smooth muscle cells and expressed at a low level in aortic endothelial cells. Expressed in the adrenal gland, predominantly in the zona glomerulosa (PubMed:29

Sequence

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

Sequence length

898

Interactions

View interactions

	KEGG		Reactome
	Mineral absorption		Stimuli-sensing channels

446

Show/Hide Causal Diseases (5)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
CLCN2-related disorder	Likely pathogenic; Pathogenic	rs201330912, rs756385625, rs201976983, rs771507094, rs863225251, rs1055985062, rs2474235576, rs2474240689, rs762516598, rs2474277095	RCV004689607 RCV004738360 RCV002510261 RCV004553102 RCV003235126 RCV003317858 RCV004550793 RCV004554163 RCV006269854 RCV004579646
Epilepsy, idiopathic generalized, susceptibility to, 11	Likely pathogenic; Pathogenic	rs201330912, rs141074059, rs756385625, rs1458831101, rs863225252, rs863225250, rs762516598, rs1293789661	RCV002490754 RCV002501901 RCV002496011 RCV001731114 RCV005031771 RCV005031769 RCV005036866 RCV002481647
Familial hyperaldosteronism type II	Likely pathogenic; Pathogenic	rs201330912, rs141074059, rs756385625, rs771507094, rs863225252, rs863225250, rs762516598, rs1085307938, rs1553853557, rs1553856214, rs1293789661, rs1553857113, rs758379595	RCV002490754 RCV002501901 RCV002496011 RCV003992233 RCV005031771 RCV005031769 RCV005036866 RCV000584655 RCV000515901 RCV000515845 RCV000516109 RCV000516045 RCV000515911
Leukoencephalopathy with mild cerebellar ataxia and white matter edema	Pathogenic; Likely pathogenic	rs1245141384, rs201330912, rs587777110, rs587777111, rs587777112, rs141074059, rs756385625, rs376823689, rs771507094, rs863225252, rs863225251, rs863225250, rs2474246529, rs762887805, rs762516598 View all (3 more)	RCV001335132 RCV000087029 RCV000087030 RCV000087031 RCV000087032 RCV002501901 RCV001693504 RCV000201824 RCV000201810 RCV000201805 RCV000201830 RCV000201803 RCV004011297 RCV003448821 RCV003994569 RCV003994782 RCV002481647 RCV001004073
Uterine corpus endometrial carcinoma	Likely pathogenic	rs141074059	RCV005916322

Show/Hide Unknown Diseases (33)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Benign	rs3749221	RCV005915413
Adrenocortical carcinoma, hereditary	Benign	rs3749221	RCV005915416
Bipolar affective disorder	Uncertain significance	rs1553856477	RCV000626861
Cerebellar ataxia	Uncertain significance	rs1553856477	RCV000626861
Cerebral palsy	Conflicting classifications of pathogenicity	rs137852682	RCV001794440
Cervical cancer	Likely benign	rs531750356	RCV005928787
Cholangiocarcinoma	Benign	rs3749221	RCV005915427
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	rs3749221	RCV005915430
Clear cell carcinoma of kidney	Benign	rs3749221	RCV005915418
CNS demyelination	Uncertain significance	rs1553856477	RCV000626861
Colon adenocarcinoma	Benign	rs3749221	RCV005915412
Colorectal cancer	Benign	rs3749221	RCV005915421
Epilepsy	Uncertain significance	rs780348130, rs778127158	RCV005361903 RCV005367660
Epilepsy, familial focal, with variable foci 2	Uncertain significance	rs2474235591	RCV003448883
EPILEPSY, JUVENILE ABSENCE, SUSCEPTIBILITY TO, 2	Uncertain significance	rs137852681	RCV000009604
EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 8	Conflicting classifications of pathogenicity	rs515726131, rs71318369	RCV000009602 RCV000009605
Familial pancreatic carcinoma	Benign	rs3749221	RCV005915420
Hepatocellular carcinoma	Likely benign; Benign	rs187000570, rs3749221	RCV005912845 RCV005915414
Hereditary ataxia	Conflicting classifications of pathogenicity	rs377119457	RCV005626699
Intellectual disability	Likely benign; Benign	rs144164281, rs114702742, rs772617403, rs780553073	RCV001251727 RCV001251939 RCV001251726 RCV001251725
Lung cancer	Benign	rs3749221	RCV005915428
Lymphoma	Benign	rs3749221	RCV005915423
Melanoma	Benign	rs3749221	RCV005915426
Nonpapillary renal cell carcinoma	Benign; Conflicting classifications of pathogenicity	rs3749221, rs371193424	RCV005915415 RCV005893614
Ovarian cancer	Benign	rs3749221, rs199948879	RCV005915417 RCV005925860
Ovarian serous cystadenocarcinoma	Benign	rs199948879	RCV005925861
Sarcoma	Benign	rs3749221	RCV005915422
See cases	Conflicting classifications of pathogenicity; Uncertain significance	rs139188499, rs150751460, rs137978189, rs143751880	RCV002252702 RCV002252704 RCV002252750 RCV002252294
Seizure	Benign; Likely benign; Uncertain significance	rs115961753, rs546781274	RCV000678790 RCV000678789
Spastic gait	Uncertain significance	rs1553856477	RCV000626861
Thymoma	Benign	rs3749221	RCV005915424
Thyroid cancer, nonmedullary, 1	Benign	rs3749221	RCV005915425
Uveal melanoma	Benign	rs3749221	RCV005915419

Show/Hide Text Mining Associations (27)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Atrial Fibrillation	Associate	31996765
Carcinoma Hepatocellular	Associate	33340691
Cerebellar Ataxia	Associate	23707145
Cognition Disorders	Associate	23707145
Cystic Fibrosis	Associate	9520461
Demyelinating Diseases	Associate	23707145
Encephalitis Herpes Simplex	Inhibit	23707145
Epilepsy	Associate	17156979, 31056551
Epilepsy Absence	Associate	17580110, 40147727
Epilepsy Idiopathic Generalized	Associate	17580110, 23632988
Epileptic Syndromes	Associate	17156979
Eye Diseases	Associate	23707145
Glioma	Associate	12843258
Headache	Associate	23707145
Hyperaldosteronism Familial Type II	Associate	29403011, 36384999
Leukodystrophy Metachromatic	Associate	23707145, 26033718
Leukoencephalopathies	Associate	23707145, 32278302, 40199115
Lymphoma	Associate	32439996
Microcephaly with Chorioretinopathy Autosomal Dominant	Associate	23707145
Muscle Spasticity	Associate	23707145
Neoplasms	Associate	26491211, 35527349
Optic Nerve Diseases	Associate	23707145
Prostatic Neoplasms	Associate	26491211, 36246902
Prostatitis	Associate	26491211
Stroke	Associate	23707145
Sudden Unexpected Death in Epilepsy	Associate	34816733
Tang Hsi Ryu syndrome	Associate	23707145

CLCN2 (chloride voltage-gated channel 2)