CLCN3 - chloride voltage-gated channel 3 Gene

Also Known as CLC3; ClC-3; NEDSBA; NEDHYBA

Species: Homo sapiens

Gene Type: protein coding
Gene ID: 1182

About CLCN3

Cytogenetic location: 4q33 Genomic coordinates (GRCh38): 4:169,620,578-169,723,673 (from NCBI)

This gene has 9 transcripts (splice variants), 209 orthologues, 8 paralogues and is associated with 5 phenotypes. Ubiquitous expression in brain (RPKM 27.7), colon (RPKM 19.9) and 25 other tissues.

Summary

This gene encodes a member of the voltage-gated Chloride Channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by CA(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

CLCN3 Products (4)

mRNA Protein Name
NM_001243372.2 NP_001230301.1 H(+)/Cl(-) exchange transporter 3 isoform a
NM_001243374.2 NP_001230303.2 H(+)/Cl(-) exchange transporter 3 isoform c
NM_001829.4 NP_001820.2 H(+)/Cl(-) exchange transporter 3 isoform b
NM_173872.4 NP_776297.2 H(+)/Cl(-) exchange transporter 3 isoform e
Molecular Function GO Annotation Evidence References Source
enables PDZ domain binding IDA
IDA: Inferred from direct assay
12471024 GOA
enables chloride channel activity IDA
IDA: Inferred from direct assay
11274166 GOA
enables protein binding IPI
IPI: Inferred from physical interaction
12471024 GOA
enables volume-sensitive chloride channel activity IMP
IMP: Inferred from mutant phenotype
12183454 GOA
Biological Process GO Annotation Evidence References Source
involved in chloride transmembrane transport IDA
IDA: Inferred from direct assay
11274166 GOA
involved in negative regulation of cell volume IMP
IMP: Inferred from mutant phenotype
12183454 GOA
Cellular Component GO Annotation Evidence References Source
is active in GABA-ergic synapse IDA
IDA: Inferred from direct assay
11182090 GOA
is active in GABA-ergic synapse IMP
IMP: Inferred from mutant phenotype
11182090 GOA
located in Golgi apparatus IDA
IDA: Inferred from direct assay
12471024 GOA
located in cytoplasmic vesicle IDA
IDA: Inferred from direct assay
11274166 GOA
located in early endosome IDA
IDA: Inferred from direct assay
12471024 GOA
located in external side of plasma membrane IDA
IDA: Inferred from direct assay
11274166 GOA
is active in glutamatergic synapse IDA
IDA: Inferred from direct assay
11182090 GOA
is active in glutamatergic synapse IMP
IMP: Inferred from mutant phenotype
11182090 GOA
located in late endosome IDA
IDA: Inferred from direct assay
12471024 GOA
located in phagocytic vesicle IDA
IDA: Inferred from direct assay
16522634 GOA
located in plasma membrane IDA
IDA: Inferred from direct assay
11274166 GOA
located in secretory granule IDA
IDA: Inferred from direct assay
16522634 GOA
located in specific granule IDA
IDA: Inferred from direct assay
16522634 GOA
located in synaptic vesicle IDA
IDA: Inferred from direct assay
11182090 GOA
is active in synaptic vesicle membrane IDA
IDA: Inferred from direct assay
11182090 GOA
is active in synaptic vesicle membrane IMP
IMP: Inferred from mutant phenotype
11182090 GOA
located in vesicle membrane IDA
IDA: Inferred from direct assay
12471024 GOA
EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

CLCN3 Protein Structure

Voltage_CLC

Voltage_CLC: Voltage gated chloride channel (221 - 622)

CBS

CBS: CBS domain (753 - 804)

  • 0
  • 200
  • 400
  • 600
  • 818 a.a.
Protein Preferred Names Protein Names

H(+)/Cl(-) exchange transporter 3

  • chloride channel 3

Related Diseases

Diseases Alias
Neurodevelopmental Disorder With Seizures And Brain Abnormalities
  • NEDSBA

Neurodevelopmental Disorder With Hypotonia And Brain Abnormalities
  • NEDHYBA

Non-Specific Syndromic Intellectual Disability
  • Complex Neurodevelopmental Disorder

Juxtacortical Chondrosarcoma
Cystic Fibrosis
  • Mucoviscidosis

  • CF

  • Pseudomonas Aeruginosa, Susceptibility To Chronic Infection By, In Cystic Fibrosis

  • Pseudomonas Aeruginosa Chronic Infection By, In Cystic Fibrosis

  • Cystic Fibrosis Lung Disease, Modifier Of

  • Cystic Fibrosis Of Pancreas

  • Fibrocystic Disease Of Pancreas

  • Cf - [Cystic Fibrosis]

  • Cystic Fibrosis Nos

  • Fibrocystic Disease

  • Fibrocystic Disease Of The Pancreas

  • Mucoviscidosis Of Pancreas

  • Nonproliferative Fibrocystic Disease

  • Pancreatic Cystic Fibrosis

Dent Disease 1
  • Dent Disease

  • Dent'S Disease

  • Dent Disease 2

  • Dent Disease Type 1

  • DENT1

  • Urolithiasis, Hypercalciuric, X-Linked

  • Nephrolithiasis 2

  • Nphl2

  • Dent Syndrome

  • Dents Disease

  • Low-Molecular-Weight Proteinuria With Hypercalciuria And Nephrocalcinosis

  • Renal Fanconi Syndrome With Nephrocalcinosis And Renal Stones

  • X-Linked Recessive Hypercalciuric Hypophosphatemic Rickets

  • X-Linked Recessive Nephrolithiasis

  • Fanconi Syndrome, Renal, With Nephrocalcinosis And Renal Stones

  • Nephrolithiasis, Hypercalciuric, X-Linked

  • Nephrolithiasis-Hypercalciuria X-Linked Recessive

  • Nephrolithiasis, X-Linked Recessive

  • Dent Disease, Type 1

Glioma
Myotonia Congenita
  • Congenital Myotonia, Autosomal Dominant Form

  • Congenital Myotonia

  • Thomsen And Becker Disease

  • Thomsen Disease

  • Thomsen'S Disease

  • Generalized Myotonia Of Thomsen

  • Congenital Myotonic Muscular Dystrophy

  • Myotonia Congenita Nos

Bartter Disease
  • Bartter Syndrome

  • Bartter'S Syndrome

  • Aldosteronism With Hyperplasia Of The Adrenal Cortex

  • Hypokalemic Alkalosis With Hypercalciuria

  • Potassium Wasting

  • Juxtaglomerular Hyperplasia With Secondary Aldosteronism

  • Renal Tubular Normotensive Hypokalemic Alkalosis With Hypercalciuria

  • Salt-Losing Tubular Disorder, Henle'S Loop Type

  • Salt-Wasting Tubulopathy, Henle'S Loop Type

  • Bartters Syndrome

Diseases Alias
Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Orthologs Information

Species Symbol Source ID
Rattus norvegicus CLCN3 RGD RGD:621219
Bos taurus CLCN3 VGNC VGNC:27397
Felis catus CLCN3 VGNC VGNC:60925
Macaca mulatta CLCN3 VGNC VGNC:71236
Canis familiaris CLCN3 VGNC VGNC:39303
Mus musculus CLCN3 MGD MGI:103555
Others CLCN3 NCBI