Seroatlas · Human Serome Atlas

CLCN6

H(+)/Cl(-) exchange transporter 6

Also known as: CLC-6, CLCN6_HUMAN, KIAA0046

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

Protein identityUniProt · HPA

UniProt accession: P51797
Gene: CLCN6
Ensembl: ENSG00000011021
Chromosome: 1
Canonical length: 869 aa
Protein class: Disease related genes, Plasma proteins, Predicted membrane proteins
Subcellular location: Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

869 residues, UniProt reviewed canonical sequence.

>P51797|CLCN6
     1  MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP
    61  YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC
   121  SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL
   181  LCKVLGVLFS VAGGLFVEKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD
   241  FVSAGAAAGV AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF
   301  GSWGSFQLPG LLNFGEFKCS DSDKKCHLWT AMDLGFFVVM GVIGGLLGAT FNCLNKRLAK
   361  YRMRNVHPKP KLVRVLESLL VSLVTTVVVF VASMVLGECR QMSSSSQIGN DSFQLQVTED
   421  VNSSIKTFFC PNDTYNDMAT LFFNPQESAI LQLFHQDGTF SPVTLALFFV LYFLLACWTY
   481  GISVPSGLFV PSLLCGAAFG RLVANVLKSY IGLGHIYSGT FALIGAAAFL GGVVRMTISL
   541  TVILIESTNE ITYGLPIMVT LMVAKWTGDF FNKGIYDIHV GLRGVPLLEW ETEVEMDKLR
   601  ASDIMEPNLT YVYPHTRIQS LVSILRTTVH HAFPVVTENR GNEKEFMKGN QLISNNIKFK
   661  KSSILTRAGE QRKRSQSMKS YPSSELRNMC DEHIASEEPA EKEDLLQQML ERRYTPYPNL
   721  YPDQSPSEDW TMEERFRPLT FHGLILRSQL VTLLVRGVCY SESQSSASQP RLSYAEMAED
   781  YPRYPDIHDL DLTLLNPRMI VDVTPYMNPS PFTVSPNTHV SQVFNLFRTM GLRHLPVVNA
   841  VGEIVGIITR HNLTYEFLQA RLRQHYQTI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLCN6 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: Other membrane
Secreted: No
Transmembrane segments: 10
Mean surface accessibility (rSASA): 0.28
Highest tissue expression: 24 nTPM

Expression across tissuesHPA

Tissue

hypothalamus: 24 nTPM
cerebral cortex: 23 nTPM
cerebellum: 22 nTPM
spinal cord: 20 nTPM
midbrain: 19 nTPM
pituitary gland: 18 nTPM

Single-cell type

cardiomyocytes: 134 nCPM
early spermatids: 74 nCPM
adrenal cortex cells: 68 nCPM
late spermatids: 68 nCPM
somatotrophs: 68 nCPM
thyrotrophs: 62 nCPM

Immune cell

non-classical monocyte: 1.6 nTPM
naive B-cell: 0.9 nTPM
classical monocyte: 0.8 nTPM
memory B-cell: 0.7 nTPM
myeloid DC: 0.7 nTPM
intermediate monocyte: 0.6 nTPM

Brain region

pons: 76 nTPM
midbrain: 70 nTPM
medulla oblongata: 57 nTPM
hypothalamus: 57 nTPM
thalamus: 54 nTPM
cerebral cortex: 48 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLCN6.

Disease | AllUniProt

Conditions CLCN6 is implicated in, by any mechanism.

Ceroid lipofuscinosis, neuronal, 15 (CLN15) MIM:619173

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 1,053 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities
12 conditions

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): 0.61
gnomAD pLI: 0
gnomAD missense Z: 1.59
DepMap mean gene effect: -0.07
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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

CBS domain
Chloride channel
Chloride channel, core
CBS domain superfamily
Voltage-gated chloride channel/antiporter
CBS domain
Voltage gated chloride channel
Chloride channel ClC-6

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CLCN6 as an antibody target. Whether an autoantibody or antibody against CLCN6 could matter depends on whether native CLCN6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CLCN6 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label CLCN6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...