CLDN16
Claudin-16
Also known as: CLD16_HUMAN, HOMG3, PCLN1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9Y5I7
- Gene
- CLDN16
- Ensembl
- ENSG00000113946
- Chromosome
- 3
- Canonical length
- 235 aa
- Protein class
- Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters
OverviewNCBI Gene
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]
Canonical amino-acid sequenceUniProt
235 residues, UniProt reviewed canonical sequence.
>Q9Y5I7|CLDN16
1 MRDLLQYIAC FFAFFSAGFL IVATWTDCWM VNADDSLEVS TKCRGLWWEC VTNAFDGIRT
61 CDEYDSILAE HPLKLVVTRA LMITADILAG FGFLTLLLGL DCVKFLPDEP YIKVRICFVA
121 GATLLIAGTP GIIGSVWYAV DVYVERSTLV LHNIFLGIQY KFGWSCWLGM AGSLGCFLAG
181 AVLTCCLYLF KDVGPERNYP YSLRKAYSAA GVSMAKSYSA PRTETAKMYA VDTRVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CLDN16 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
- 4
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 59 nTPM
Expression across tissuesHPA
Tissue
- kidney: 59 nTPM
- thyroid gland: 9 nTPM
- skin: 3 nTPM
- fallopian tube: 2.7 nTPM
- liver: 2.1 nTPM
- lymph node: 1.4 nTPM
Single-cell type
- ocular epithelial cells: 194 nCPM
- epididymal basal cells: 122 nCPM
- respiratory ciliated cells: 99 nCPM
- loop of henle epithelial cells: 90 nCPM
- choroid plexus epithelial cells: 83 nCPM
- epididymal efferent duct ciliated cells: 67 nCPM
Immune cell
- basophil: 0.1 nTPM
- neutrophil: 0.1 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- choroid plexus: 4 nTPM
- white matter: 1.9 nTPM
- cerebral cortex: 1.8 nTPM
- basal ganglia: 1.5 nTPM
- amygdala: 1.2 nTPM
- hypothalamus: 1.2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CLDN16.
Disease | AllUniProt
Conditions CLDN16 is implicated in, by any mechanism.
- Hypomagnesemia 3 (HOMG3) MIM:248250
Disease | GeneticClinVar
48 pathogenic / likely-pathogenic of 276 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Primary hypomagnesemia
- HYPERCALCIURIA, CHILDHOOD, SELF-LIMITING
- Renal hypomagnesemia 5 with ocular involvement
- Thrombocytopenia 5
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)
- 0.76
- gnomAD pLI
- 0.03
- gnomAD missense Z
- -0.08
- DepMap mean gene effect
- 0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- bicellular tight junction assembly
- calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
- cell adhesion
- intracellular monoatomic cation homeostasis
- metal ion transport
- paracellular transport
- renal absorption
- intercellular transport
Molecular functions
- identical protein binding
- magnesium ion transmembrane transporter activity
- paracellular tight junction channel activity
- PDZ domain binding
- structural molecule activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CLDN16 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 CLDN16 as an antibody target. Whether an autoantibody or antibody against CLDN16 could matter depends on whether native CLDN16 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CLDN16 is annotated at the cell surface, where native CLDN16 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 CLDN16 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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