Seroatlas · Human Serome Atlas

CLCN2

Chloride channel protein 2

Also known as: ClC-2, CLC2, CLCN2_HUMAN, EJM6

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P51788
Gene
CLCN2
Ensembl
ENSG00000114859
Chromosome
3
Canonical length
898 aa
Protein class
Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins, Transporters
Subcellular location
Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

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 different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

898 residues, UniProt reviewed canonical sequence.

>P51788|CLCN2
     1  MAAAAAEEGM EPRALQYEQT LMYGRYTQDL GAFAKEEAAR IRLGGPEPWK GPPSSRAAPE
    61  LLEYGRSRCA RCRVCSVRCH KFLVSRVGED WIFLVLLGLL MALVSWVMDY AIAACLQAQQ
   121  WMSRGLNTSI LLQYLAWVTY PVVLITFSAG FTQILAPQAV GSGIPEMKTI LRGVVLKEYL
   181  TLKTFIAKVI GLTCALGSGM PLGKEGPFVH IASMCAALLS KFLSLFGGIY ENESRNTEML
   241  AAACAVGVGC CFAAPIGGVL FSIEVTSTFF AVRNYWRGFF AATFSAFIFR VLAVWNRDEE
   301  TITALFKTRF RLDFPFDLQE LPAFAVIGIA SGFGGALFVY LNRKIVQVMR KQKTINRFLM
   361  RKRLLFPALV TLLISTLTFP PGFGQFMAGQ LSQKETLVTL FDNRTWVRQG LVEELEPPST
   421  SQAWNPPRAN VFLTLVIFIL MKFWMSALAT TIPVPCGAFM PVFVIGAAFG RLVGESMAAW
   481  FPDGIHTDSS TYRIVPGGYA VVGAAALAGA VTHTVSTAVI VFELTGQIAH ILPVMIAVIL
   541  ANAVAQSLQP SLYDSIIRIK KLPYLPELGW GRHQQYRVRV EDIMVRDVPH VALSCTFRDL
   601  RLALHRTKGR MLALVESPES MILLGSIERS QVVALLGAQL SPARRRQHMQ ERRATQTSPL
   661  SDQEGPPTPE ASVCFQVNTE DSAFPAARGE THKPLKPALK RGPSVTRNLG ESPTGSAESA
   721  GIALRSLFCG SPPPEAASEK LESCEKRKLK RVRISLASDA DLEGEMSPEE ILEWEEQQLD
   781  EPVNFSDCKI DPAPFQLVER TSLHKTHTIF SLLGVDHAYV TSIGRLIGIV TLKELRKAIE
   841  GSVTAQGVKV RPPLASFRDS ATSSSDTETT EVHALWGPHS RHGLPREGSP SDSDDKCQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLCN2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
10
Mean surface accessibility (rSASA)
0.37
Highest tissue expression
15 nTPM

Expression across tissuesHPA

Tissue

  • colon: 15 nTPM
  • testis: 10 nTPM
  • rectum: 10 nTPM
  • duodenum: 8.7 nTPM
  • small intestine: 8.1 nTPM
  • gallbladder: 7.1 nTPM

Single-cell type

  • retinal pigment epithelial cells: 85 nCPM
  • colonocytes: 66 nCPM
  • sertoli cells: 34 nCPM
  • enterocytes: 28 nCPM
  • retinal ganglion cells: 23 nCPM
  • astrocytes: 23 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • white matter: 9.2 nTPM
  • medulla oblongata: 7.4 nTPM
  • thalamus: 7 nTPM
  • cerebellum: 6.8 nTPM
  • basal ganglia: 6.7 nTPM
  • midbrain: 6.5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLCN2.

Disease | AllUniProt

Conditions CLCN2 is implicated in, by any mechanism.

Disease | GeneticClinVar

46 pathogenic / likely-pathogenic of 706 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Leukoencephalopathy with mild cerebellar ataxia and white matter edema
  • Familial hyperaldosteronism type II
  • Epilepsy, idiopathic generalized, susceptibility to, 11
  • CLCN2-related disorder
  • Uterine corpus endometrial carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.77
gnomAD pLI
0
gnomAD missense Z
0.65
DepMap mean gene effect
0.01
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CLCN2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CLCN2 as an antibody target. Whether an autoantibody or antibody against CLCN2 could matter depends on whether native CLCN2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CLCN2 is annotated at the cell surface, where native CLCN2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label CLCN2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CLCN2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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