CLDN16
Claudin-16: A Key Tight Junction Protein in Renal Magnesium and Calcium Homeostasis
Gene Information Card
| Symbol | CLDN16 |
|---|---|
| Full Name | Claudin 16 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q28 |
| NCBI Gene ID | 10686 ncbi.nlm.nih.gov/gene/10686 |
| Ensembl ID | ENSG00000113946 |
| UniProt ID | Q9Y5I7 |
| OMIM ID | 603959 |
| HGNC ID | 2037 |
| Aliases | PCLN1, paracellin-1, hPCLN1 |
Description
CLDN16 encodes claudin-16 (also known as paracellin-1), a member of the claudin family of tight junction proteins. Claudin-16 is predominantly expressed in the thick ascending limb of Henle's loop in the kidney, where it forms paracellular channels selective for magnesium and calcium ions. It is essential for the reabsorption of these divalent cations, and loss-of-function mutations lead to renal magnesium wasting, hypercalciuria, and nephrocalcinosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) | Loss-of-function mutations in CLDN16 disrupt paracellular magnesium and calcium reabsorption in the thick ascending limb, leading to renal wasting of these ions, hypercalciuria, nephrocalcinosis, and progressive renal failure. | OMIM #248250; multiple reports in ClinVar and literature. |
| Hypomagnesemia 3, renal | Same mechanism as FHHNC; some mutations cause a milder phenotype with predominant hypomagnesemia. | OMIM #248250; ClinVar. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Testis | 1.2 | Low |
| Pancreas | 0.8 | Low |
| Liver | 0.5 | Not detected |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.1 | Low endogenous expression; used for heterologous expression studies. |
| MDCK | 0.2 | Canine kidney cell line; used for tight junction studies. |
| HK-2 | 0.5 | Human proximal tubule cell line; low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.593G>A (p.Gly198Asp) | Missense | Common in FHHNC | Loss of function; disrupts ion selectivity. |
| c.716T>C (p.Leu239Pro) | Missense | Rare | Loss of function; impaired trafficking to tight junctions. |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein synthesis. |
| c.488C>T (p.Thr163Met) | Missense | Rare | Loss of function; reduced paracellular Mg2+ permeability. |
Mutation functional classification
Loss of Function (LOF)
Most CLDN16 mutations are loss-of-function, impairing paracellular Mg2+ and Ca2+ permeability in the thick ascending limb, leading to FHHNC.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLDN16.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type claudin-16 assembly, but most are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tight junction (KEGG: hsa04530)
• Paracellular ion transport (Reactome: R-HSA-420029)
Protein Summary
Claudin-16 is a 305-amino-acid transmembrane protein with four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. It localizes to tight junctions of renal epithelial cells in the thick ascending limb of Henle's loop. The protein forms paracellular pores that selectively allow the passage of magnesium and calcium ions, driven by the transepithelial voltage. Mutations in CLDN16 disrupt this selectivity, causing renal magnesium and calcium wasting. The protein interacts with other claudins (e.g., claudin-19) to form heteromeric channels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN16 Knockout HEK293 Cell Line | EDJ-KQ7130 | Human | 10686 | Details Get a Quote |
| CLDN16 Knockout HeLa Cell Line | EDJ-KQ55462 | Human | 10686 | Details Get a Quote |
| CLDN16 Knockout A-549 Cell Line | EDJ-KQ63947 | Human | 10686 | Details Get a Quote |
| CLDN16 Knockout HCT 116 Cell Line | EDJ-KQ72404 | Human | 10686 | Details Get a Quote |
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