Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	10	898	3q27.1	CLCN2	chloride voltage-gated channel 2
Mouse	10	908	16 12.5 cM	Clcn2	chloride channel, voltage-sensitive 2
Rat	10	907	11q23	Clcn2	chloride voltage-gated channel 2

Previous and Unofficial Names

CLC2 | chloride channel 2 | EJM6 | chloride channel, voltage-sensitive 2 | chloride channel

Database Links
Alphafold	P51788 (Hs), Q9R0A1 (Mm), P35525 (Rn)
CATH/Gene3D	1.10.3080.10
ChEMBL Target	CHEMBL1628478 (Hs)
DrugBank Target	P51788 (Hs)
Ensembl Gene	ENSG00000114859 (Hs), ENSMUSG00000022843 (Mm), ENSRNOG00000001742 (Rn)
Entrez Gene	1181 (Hs), 12724 (Mm), 29232 (Rn)
Human Protein Atlas	ENSG00000114859 (Hs)
KEGG Gene	hsa:1181 (Hs), mmu:12724 (Mm), rno:29232 (Rn)
OMIM	600570 (Hs)
Orphanet	ORPHA226047 (Hs)
Pharos	P51788 (Hs)
UniProtKB	P51788 (Hs), Q9R0A1 (Mm), P35525 (Rn)
Wikipedia	CLCN2 (Hs)

Functional Characteristics

γ = 2-3 pS; voltage-activated by membrane hyperpolarization by fast protopore and slow cooperative gating; channels only open negative to ECl resulting in steady-state inward rectification; voltage dependence modulated by permeant anions; activated by cell swelling, PKA, and weak extracellular acidosis; potentiated by SGK1; inhibited by phosphorylation by p34(cdc2)/cyclin B; cell surface expression and activity increased by association with Hsp90

Natural/Endogenous Ligands
arachidonic acid

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference arachidonic acid Hs - - - - no ⤷ Not voltage dependent lubiprostone Hs - - - - no ⤷ Not voltage dependent omeprazole Hs - - - - no ⤷ Not voltage dependent
Activator Comments
CIC-2 is also activated by amidation.

Channel Blockers
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference GaTx2 Hs - 10.8 pKd - yes (-100.0) ⤷ pKd 10.8 (Kd 1.5x10-11 M) Voltage dependent: -100.0 mV Zn2+ Hs - - - - no ⤷ Not voltage dependent Cd2+ Hs - - - - no ⤷ Not voltage dependent diphenylamine-2-carboxylic acid Hs - - - - no ⤷ Not voltage dependent NPPB Hs - - - - no ⤷ Not voltage dependent

Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy, idiopathic generalized, susceptibility to, 11; EIG11 Synonyms: Idiopathic generalized epilepsy [Disease Ontology: DOID:1827] Disease Ontology: DOID:1827 OMIM: 607628
Disease:  Epilepsy, juvenile myoclonic, susceptibility to, 8; EJM8 Synonyms: Juvenile myoclonic epilepsy [Orphanet: ORPHA307] [Disease Ontology: DOID:4890] Disease Ontology: DOID:4890 OMIM: 607628 Orphanet: ORPHA307
Disease:  Leukoencephalopathy with mild cerebellar ataxia and white matter edema OMIM: 615651 Orphanet: ORPHA363540 References:  1