Seroatlas · Human Serome Atlas

CLCN5

H(+)/Cl(-) exchange transporter 5

Also known as: ClC-5, CLC5, CLCN5_HUMAN, DENTS, hCIC-K2, hClC-K2, NPHL1, NPHL2, XLRH, XRN

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

Protein identityUniProt · HPA

UniProt accession: P51795
Gene: CLCN5
Ensembl: ENSG00000171365
Chromosome: X
Canonical length: 816 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location: Golgi apparatus,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

Canonical amino-acid sequenceUniProt

816 residues, UniProt reviewed canonical sequence.

>P51795|CLCN5
     1  MAMWQGAMDN RGFQQGSFSS FQNSSSDEDL MDIPATAMDF SMRDDVPPLD REVGEDKSYN
    61  GGGIGSSNRI MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNKS KESTWALIHS
   121  VSDAFSGWLL MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TGGFWFNHEH CCWNSEHVTF
   181  EERDKCPEWN SWSQLIISTD EGAFAYIVNY FMYVLWALLF AFLAVSLVKV FAPYACGSGI
   241  PEIKTILSGF IIRGYLGKWT LVIKTITLVL AVSSGLSLGK EGPLVHVACC CGNILCHCFN
   301  KYRKNEAKRR EVLSAAAAAG VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF
   361  TLRSINPFGN SRLVLFYVEF HTPWHLFELV PFILLGIFGG LWGALFIRTN IAWCRKRKTT
   421  QLGKYPVIEV LVVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL CDYENRFNTS
   481  KGGELPDRPA GVGVYSAMWQ LALTLILKIV ITIFTFGMKI PSGLFIPSMA VGAIAGRLLG
   541  VGMEQLAYYH QEWTVFNSWC SQGADCITPG LYAMVGAAAC LGGVTRMTVS LVVIMFELTG
   601  GLEYIVPLMA AAMTSKWVAD ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR
   661  NDPLLTVLTQ DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKK
   721  QDGVVSTSII YFTEHSPPLP PYTPPTLKLR NILDLSPFTV TDLTPMEIVV DIFRKLGLRQ
   781  CLVTHNGRLL GIITKKDVLK HIAQMANQDP DSILFN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLCN5 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): 0.28
Highest tissue expression: 43 nTPM

Expression across tissuesHPA

Tissue

kidney: 43 nTPM
epididymis: 22 nTPM
liver: 16 nTPM
ovary: 6.6 nTPM
placenta: 5.5 nTPM
duodenum: 4.6 nTPM

Single-cell type

myosatellite cells: 714 nCPM
distal convoluted tubule cells: 453 nCPM
loop of henle epithelial cells: 447 nCPM
renal connecting tubule cells: 218 nCPM
proximal tubule cells: 174 nCPM
pdcs: 146 nCPM

Immune cell

plasmacytoid DC: 2.8 nTPM
myeloid DC: 2.6 nTPM
classical monocyte: 0.9 nTPM
intermediate monocyte: 0.9 nTPM
total PBMC: 0.3 nTPM
memory CD4 T-cell: 0.2 nTPM

Brain region

pons: 9.4 nTPM
cerebellum: 9.3 nTPM
medulla oblongata: 8.4 nTPM
midbrain: 8.3 nTPM
hypothalamus: 7.7 nTPM
thalamus: 7.5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLCN5.

Disease | AllUniProt

Conditions CLCN5 is implicated in, by any mechanism.

Hypophosphatemic rickets, X-linked recessive (XLHRR) MIM:300554
Dent disease 1 (DENT1) MIM:300009
Nephrolithiasis, X-linked recessive, with renal failure (XRN) MIM:310468
Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) MIM:308990

Disease | GeneticClinVar

146 pathogenic / likely-pathogenic of 652 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Dent disease type 1
Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis
X-linked recessive nephrolithiasis with renal failure
Hypophosphatemic rickets, X-linked recessive
CLCN5-related disorder

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): 0.28
gnomAD pLI: 0.99
gnomAD missense Z: 2.53
DepMap mean gene effect: 0.09
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 CLCN5 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 CLCN5 as an antibody target. Whether an autoantibody or antibody against CLCN5 could matter depends on whether native CLCN5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CLCN5 is annotated at the cell surface, where native CLCN5 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 CLCN5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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