CLDN12: Claudin-12 - Tight Junction Protein and Barrier Function
Comprehensive genomic and proteomic analysis of CLDN12, a member of the claudin family involved in paracellular ion transport and blood-brain barrier integrity.
Gene Information Card
| Symbol | CLDN12 |
|---|---|
| Full Name | Claudin 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q21.13 |
| NCBI Gene ID | 9069 ncbi.nlm.nih.gov/gene/9069 |
| Ensembl ID | ENSG00000177272 |
| UniProt ID | P56749 |
| OMIM ID | 611787 |
| HGNC ID | 2042 |
| Aliases | claudin-12, CLD12 |
Description
CLDN12 (Claudin 12) is a protein-coding gene that belongs to the claudin family of tight junction proteins. Claudins are integral membrane proteins that form the backbone of tight junction strands and regulate paracellular ion selectivity and barrier function. CLDN12 is specifically involved in the formation of tight junctions in endothelial and epithelial cells, contributing to the blood-brain barrier and ion homeostasis. It is expressed in various tissues including brain, kidney, and intestine.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (HSP) | Mutations in CLDN12 may disrupt tight junction integrity in the central nervous system, leading to axonal degeneration. | PMID: 28492530 |
| Inflammatory bowel disease (IBD) | Altered CLDN12 expression in intestinal epithelium contributes to increased paracellular permeability and mucosal inflammation. | PMID: 29102620 |
| Brain edema / stroke | Downregulation of CLDN12 in cerebral endothelial cells compromises blood-brain barrier function, exacerbating edema. | PMID: 25634563 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.3 | Low |
| Intestine | 6.7 | Low |
| Lung | 4.2 | Not detected |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| hCMEC/D3 (brain endothelial) | 15.2 | High expression; relevant for blood-brain barrier studies |
| Caco-2 (intestinal epithelial) | 9.8 | Moderate expression; tight junction model |
| HEK293 (embryonic kidney) | 5.4 | Low expression; used for heterologous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Pro67Leu) | Missense | <0.01% | Potential loss of tight junction integrity |
| c.487G>A (p.Val163Met) | Missense | <0.01% | Unknown functional impact |
| c.1A>G (p.Met1?) | Start loss | Rare | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro67Leu) may disrupt claudin-12 folding or polymerization, impairing tight junction barrier function.
Gain of Function (GOF)
No gain-of-function mutations reported for CLDN12.
Dominant Negative (DN)
No dominant-negative mutations described; claudin-12 likely acts as a co-polymerizing subunit.
View complete mutation data：
Gene Ontology (GO)
| • bicellular tight junction (GO:0005923) | • structural molecule activity (GO:0005198) |
| • lateral plasma membrane (GO:0016328) | • cell junction (GO:0030054) |
| • keratin filament (GO:0045095) |
Pathways
• Tight junction (KEGG: hsa04530)
• Cell junction organization (Reactome: R-HSA-446728)
• Blood-brain barrier and immune cell transmigration (Reactome: R-HSA-2168880)
Protein Summary
Claudin-12 is a 27 kDa transmembrane protein with four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. It localizes to tight junctions and interacts with other claudins and scaffolding proteins such as ZO-1. The extracellular loops mediate paracellular ion selectivity, particularly for cations. Post-translational modifications include palmitoylation and phosphorylation, which regulate trafficking and stability. CLDN12 is critical for maintaining the blood-brain barrier and renal ion reabsorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN12 Knockout HEK293 Cell Line | EDJ-KQ5771 | Human | 9069 | Details Get a Quote |
| CLDN12 Knockout A-549 Cell Line | EDJ-KQ30518 | Human | 9069 | Details Get a Quote |
| CLDN12 Knockout HCT 116 Cell Line | EDJ-KQ30520 | Human | 9069 | Details Get a Quote |
| CLDN12 Knockout HeLa Cell Line | EDJ-KQ30521 | Human | 9069 | Details Get a Quote |
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