CLDN16 claudin 16 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLDN16provided by HGNC
Official Full Name: claudin 16provided by HGNC
Primary source: HGNC:HGNC:2037
See related: Ensembl:ENSG00000113946 MIM:603959; AllianceGenome:HGNC:2037
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HOMG3; PCLN1
Summary: 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]
Expression: Biased expression in kidney (RPKM 20.4), thyroid (RPKM 4.2) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 3q28

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (190290361..190412138)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (193106655..193228453)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (190008150..190129927)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Novel Mutation in CLDN16 Gene Causing Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis in An Iranian Family.
Title: A Novel Mutation in CLDN16 Gene Causing Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis in An Iranian Family.
To gain more understanding about the mechanisms by which CLDN16 mutations can induce FHHNC, we performed an in-depth computational analysis of the CLDN16 gene and protein, focusing specifically on the prediction of the latter's subcellular localization.
Title: In-Depth Bioinformatic Study of the CLDN16 Gene and Protein: Prediction of Subcellular Localization to Mitochondria.
No significant associations were found among claudin-16 and claudin-19 single-nucleotide polymorphisms and calcium excretion and between claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms and stones.
Title: Claudin-14 Gene Polymorphisms and Urine Calcium Excretion.
This study demonstrated that a female-specific role clnd16 in tau pathology
Title: Sex-specific genetic predictors of Alzheimer's disease biomarkers.
Mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule.
Title: Exonic CLDN16 mutations associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis can induce deleterious mRNA alterations.
Results show that CLDN16 mutation c.602G>A had no effect on pre-mRNA splicing in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. This study expands the genotypic classification of this rare disease and provides the first report of a CLDN19 mutation affecting splicing.
Title: Characterization of two novel mutations in the claudin-16 and claudin-19 genes that cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Data suggest that Pdzrn3 mediates endocytosis of dephosphorylated CLDN16 and represents an important component of CLDN16-trafficking machinery in renal tube epithelial cells. (Pdzrn3 = PDZ domain containing RING finger 3 protein; CLDN16 = claudin 16)
Title: The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the Mg(2+) regulator claudin-16 in renal tube epithelial cells.
detected a novel mutation in CLDN16 for the first time. The clinical and genetic findings from this study will help to expand the understanding of this rare disease, FHHNC
Title: A novel mutation in CLDN16 results in rare familial hypomagnesaemia with hypercalciuria and nephrocalcinosis in a Chinese family.
claudin-16 gene (CLDN16) mutations result in amelogenesis imperfect.
Title: Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.
CLDN16 mutations are associated with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.
Title: Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Primary hypomagnesemia MedGen: C0268448 OMIM: 248250 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC156606P4 (e-PCR)
- UniSTS:271411

D8S2279 (e-PCR)
- UniSTS:473907

NoName (e-PCR)
- UniSTS:483932

SHGC-33716 (e-PCR)
- UniSTS:25753

CLDN16_1935 (e-PCR)
- UniSTS:280504

NoName (e-PCR)
- UniSTS:481728

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables PDZ domain binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables magnesium ion transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
enables paracellular tight junction channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural molecule activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in bicellular tight junction assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in intercellular transport	TAS Traceable Author Statement more info	PubMed
involved_in intracellular monoatomic cation homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in magnesium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in metal ion transport	TAS Traceable Author Statement more info	PubMed
involved_in paracellular transport	IDA Inferred from Direct Assay more info	PubMed
involved_in renal absorption	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in bicellular tight junction	IBA Inferred from Biological aspect of Ancestor more info
located_in bicellular tight junction	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in tight junction	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: claudin-16

Names: hypomagnesemia 3, with hypercalciuria and nephrocalcinosis; paracellin-1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008149.2 RefSeqGene

Range

102803..126778

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001378492.1 → NP_001365421.1 claudin-16

Status: REVIEWED

Source sequence(s)

AC009520, AC080006

Consensus CDS

CCDS3296.2

UniProtKB/Swiss-Prot

Q9Y5I7

Conserved Domains (1) summary

cl21598
Location:11 → 183

PMP22_Claudin; PMP-22/EMP/MP20/Claudin family
NM_001378493.1 → NP_001365422.1 claudin-16

Status: REVIEWED

Source sequence(s)

AC009520, AC080006

Consensus CDS

CCDS3296.2

UniProtKB/Swiss-Prot

Q9Y5I7

Conserved Domains (1) summary

cl21598
Location:11 → 183

PMP22_Claudin; PMP-22/EMP/MP20/Claudin family
NM_006580.4 → NP_006571.2 claudin-16

Status: REVIEWED

Source sequence(s)

AC009520

Consensus CDS

CCDS3296.2

UniProtKB/Swiss-Prot

Q9Y5I7

Related

ENSP00000264734.3, ENST00000264734.3

Conserved Domains (1) summary

cl21598
Location:11 → 183

PMP22_Claudin; PMP-22/EMP/MP20/Claudin family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

190290361..190412138

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047447333.1 → XP_047303289.1 claudin-16 isoform X1

UniProtKB/Swiss-Prot

Q9Y5I7

Conserved Domains (1) summary

cl21598
Location:11 → 183

PMP22_Claudin; PMP-22/EMP/MP20/Claudin family