Details for: CLDN12

Gene ID: 9069

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CLDN12

Ensembl ID: ENSG00000157224

Description: claudin 12

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • lung neuroendocrine cell CL1000223
    CSI 8.01
    rCSI 11.84%
    PRS 86.89
  • type B pancreatic cell CL0000169
    CSI 7.36
    rCSI 16.28%
    PRS 83.66
  • choroid plexus epithelial cell CL0000706
    CSI 7.14
    rCSI 11.69%
    PRS 74.39
  • VIP GABAergic cortical interneuron CL4023016
    CSI 5.85
    rCSI 6.99%
    PRS 67.33
  • intestine goblet cell CL0019031
    CSI 4.41
    rCSI 3.91%
    PRS 81.72
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.13
    rCSI 5.13%
    PRS 65.19
  • pancreatic D cell CL0000173
    CSI 3.35
    rCSI 3.29%
    PRS 86.09
  • ciliated epithelial cell CL0000067
    CSI 3.35
    rCSI 2.94%
    PRS 73.92
  • stem cell CL0000034
    CSI 3.2
    rCSI 3.09%
    PRS 78.33
  • ON-bipolar cell CL0000749
    CSI 3.17
    rCSI 4.71%
    PRS 83.51
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.09
    rCSI 2.4%
    PRS 87.32
  • secretory cell CL0000151
    CSI 3.01
    rCSI 3.15%
    PRS 83.25
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.99
    rCSI 3.85%
    PRS 68.44
  • epithelial cell of lung CL0000082
    CSI 2.97
    rCSI 2.46%
    PRS 85
  • ionocyte CL0005006
    CSI 2.79
    rCSI 2.99%
    PRS 85.79
  • epithelial cell CL0000066
    CSI 2.79
    rCSI 4.29%
    PRS 72.83
  • neural crest cell CL0011012
    CSI 2.78
    rCSI 2.2%
    PRS 74.22
  • hepatic stellate cell CL0000632
    CSI 2.78
    rCSI 10.43%
    PRS 77.04
  • goblet cell CL0000160
    CSI 2.72
    rCSI 2.57%
    PRS 82.22
  • intestinal epithelial cell CL0002563
    CSI 2.6
    rCSI 2.72%
    PRS 81.55
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.58
    rCSI 3.66%
    PRS 81.11
  • fibroblast of lung CL0002553
    CSI 2.58
    rCSI 2.4%
    PRS 84.79
  • renal alpha-intercalated cell CL0005011
    CSI 2.5
    rCSI 3.35%
    PRS 89.11
  • rod bipolar cell CL0000751
    CSI 2.32
    rCSI 4.18%
    PRS 77.76
  • retina horizontal cell CL0000745
    CSI 2.3
    rCSI 3.51%
    PRS 80.84
  • interneuron CL0000099
    CSI 2.29
    rCSI 4.6%
    PRS 75.35
  • Mueller cell CL0000636
    CSI 2.27
    rCSI 5.18%
    PRS 75.96
  • lung ciliated cell CL1000271
    CSI 2.25
    rCSI 2.6%
    PRS 77.02
  • ependymal cell CL0000065
    CSI 2.25
    rCSI 4.56%
    PRS 63.6
  • duct epithelial cell CL0000068
    CSI 2.24
    rCSI 3.28%
    PRS 88.38
  • hepatocyte CL0000182
    CSI 2.21
    rCSI 3.95%
    PRS 83.16
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.15
    rCSI 5.44%
    PRS 75.3
  • colon epithelial cell CL0011108
    CSI 2.11
    rCSI 2.21%
    PRS 81.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.09
    rCSI 2.08%
    PRS 78.11
  • intestinal tuft cell CL0019032
    CSI 2.07
    rCSI 3.17%
    PRS 87.17
  • chondrocyte CL0000138
    CSI 2.05
    rCSI 3.26%
    PRS 77.52
  • periportal region hepatocyte CL0019026
    CSI 2.03
    rCSI 7.88%
    PRS 82.38
  • pancreatic acinar cell CL0002064
    CSI 2
    rCSI 2.66%
    PRS 88.63
  • mucus secreting cell CL0000319
    CSI 1.98
    rCSI 3.14%
    PRS 90.89
  • lung secretory cell CL1000272
    CSI 1.98
    rCSI 4.89%
    PRS 84.15
  • retinal bipolar neuron CL0000748
    CSI 1.88
    rCSI 3.52%
    PRS 73.19
  • direct pathway medium spiny neuron CL4023026
    CSI 1.84
    rCSI 44.05%
    PRS 65.15
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.81
    rCSI 43.78%
    PRS 65.64
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.75
    rCSI 3.09%
    PRS 66.83
  • OFF-bipolar cell CL0000750
    CSI 1.69
    rCSI 2.32%
    PRS 84.81
  • epithelial cell of proximal tubule CL0002306
    CSI 1.63
    rCSI 3.99%
    PRS 76.5
  • inhibitory interneuron CL0000498
    CSI 1.63
    rCSI 3.75%
    PRS 72.51
  • colonocyte CL1000347
    CSI 1.59
    rCSI 2.27%
    PRS 83.78
  • cardiac muscle cell CL0000746
    CSI 1.56
    rCSI 2.24%
    PRS 74.44
  • colon goblet cell CL0009039
    CSI 1.51
    rCSI 3.59%
    PRS 87.88
  • enterocyte CL0000584
    CSI 1.49
    rCSI 2.4%
    PRS 82.36
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.42
    rCSI 3.68%
    PRS 79.92
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.39
    rCSI 2.23%
    PRS 68.66
  • retinal cone cell CL0000573
    CSI 1.26
    rCSI 2.02%
    PRS 74.71
  • pancreatic ductal cell CL0002079
    CSI 1.25
    rCSI 2.44%
    PRS 86.79
  • retinal ganglion cell CL0000740
    CSI 1.25
    rCSI 2.76%
    PRS 70.65
  • medium spiny neuron CL1001474
    CSI 1.21
    rCSI 10.45%
    PRS 72.85
  • stratified epithelial cell CL0000079
    CSI 1.21
    rCSI 7.47%
    PRS 90.04
  • regular atrial cardiac myocyte CL0002129
    CSI 1.11
    rCSI 3.57%
    PRS 80.76
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.02
    rCSI 6.35%
    PRS 76.29
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.93
    rCSI 2.26%
    PRS 65.12
  • luminal cell of prostate epithelium CL0002340
    CSI 0.93
    rCSI 4.98%
    PRS 90.24
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.89
    rCSI 1.49%
    PRS 67.2
  • glial cell CL0000125
    CSI 0.88
    rCSI 3.36%
    PRS 75.53
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.86
    rCSI 2.05%
    PRS 71.23
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.83
    rCSI 2.59%
    PRS 68.77
  • podocyte CL0000653
    CSI 0.82
    rCSI 3.65%
    PRS 84.66
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.77
    rCSI 2.77%
    PRS 65.15
  • deuterosomal cell CL4033044
    CSI 0.74
    rCSI 2.5%
    PRS 80.44
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.63
    rCSI 2.38%
    PRS 67.7
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.61
    rCSI 1.91%
    PRS 71.08
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.53
    rCSI 3.1%
    PRS 67.69
  • ON midget ganglion cell CL4033046
    CSI 0.29
    rCSI 5.98%
    PRS 74.03

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CLDN12](/details-gene/9069) is a protein-coding gene that encodes claudin-12, a member of the claudin family of transmembrane proteins. These proteins are integral components of tight junctions, which are essential for regulating paracellular permeability and maintaining cell polarity in epithelial and endothelial cell sheets. Functionally, [CLDN12](/details-gene/9069) is involved in calcium-independent cell-cell adhesion and the assembly and maintenance of tight junctions, including those that form the blood-brain barrier. **Overall**, its expression is most significant in specialized secretory and barrier-forming cells, such as [lung neuroendocrine cell](/details-cell/CL1000223), [type B pancreatic cell](/details-cell/CL0000169), and [choroid plexus epithelial cell](/details-cell/CL0000706), suggesting a crucial role in tissues requiring strict control over molecular transport and intercellular communication. ## Cellular Roles and Expression Landscape The expression profile of [CLDN12](/details-gene/9069) highlights its importance in a diverse set of specialized cell types responsible for secretion and barrier formation. **Overall**, it shows the highest significance in [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 8.01), pancreatic endocrine cells like the [type B pancreatic cell](/details-cell/CL0000169) (CSI: 7.36) and [pancreatic D cell](/details-cell/CL0000173) (CSI: 3.35), and the [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 7.14), which forms the blood-cerebrospinal fluid barrier. This pattern suggests a fundamental role for [CLDN12](/details-gene/9069) in regulating the microenvironment of glandular and neural tissues. Its high significance is also noted in various secretory and epithelial cells, including [intestine goblet cell](/details-cell/CL0019031), [ciliated epithelial cell](/details-cell/CL0000067), and [epithelial cell of lung](/details-cell/CL0000082). Furthermore, its expression in specific neuronal subtypes, such as [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), points towards a potential, though less characterized, role in forming specialized cell junctions within the central nervous system. The collective expression data strongly indicates that [CLDN12](/details-gene/9069) is a key structural component in tissues that rely on tight junction integrity for their primary functions. ## Pathways and Molecular Function The functions of [CLDN12](/details-gene/9069) are intrinsically linked to its role as a core component of tight junctions. Gene Ontology annotations confirm its participation in [Calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules](/details-go/GO:0016338) and [Tight junction assembly](/details-go/GO:0120192). It is localized to the [bicellular tight junction](/details-go/GO:0005923) and the [lateral plasma membrane](/details-go/GO:0016328), consistent with its structural function. Reactome pathway analysis further situates [CLDN12](/details-gene/9069) within the broader processes of [Cell junction organization](/details-pathway/R-HSA-446728) and specifically [Tight junction interactions](/details-pathway/R-HSA-420029). This is highly consistent with its prominent expression in [choroid plexus epithelial cell](/details-cell/CL0000706), as it is annotated with a role in the [Maintenance of blood-brain barrier](/details-go/GO:0035633). Beyond its structural role, research has indicated that [CLDN12](/details-gene/9069) can serve as a host factor for pathogen entry, as it was shown to associate with CD81 to mediate hepatitis C virus entry ([Link](https://doi.org/10.1074/jbc.m110.104836)). This finding reveals a direct link between its molecular function and clinical pathology. ## Research Directions The specific expression patterns and known functions of [CLDN12](/details-gene/9069) suggest several avenues for future investigation, particularly concerning its role in tissue-specific physiology and disease. **Proposed Hypotheses:** 1. Given its high significance in pancreatic islet cells ([type B pancreatic cell](/details-cell/CL0000169), [pancreatic D cell](/details-cell/CL0000173)), [CLDN12](/details-gene/9069) may be essential for the structural organization of islets and the paracrine signaling required for coordinated hormone release. Its dysregulation could contribute to islet dysfunction in metabolic diseases like diabetes. 2. The prominent role of [CLDN12](/details-gene/9069) in [choroid plexus epithelial cell](/details-cell/CL0000706) and its annotated function in blood-brain barrier maintenance suggest it is a critical gatekeeper of the blood-cerebrospinal fluid barrier. Variations in its expression or function might influence susceptibility to neuroinflammatory conditions or affect the CNS penetration of therapeutic drugs. **Experimental Approach:** To test the role of [CLDN12](/details-gene/9069) in pancreatic islet function (Hypothesis 1), one could utilize a cell-type-specific knockout mouse model, deleting *Cldn12* in pancreatic beta cells. *Ex vivo* perifusion studies on isolated islets from these mice could be performed to measure glucose-stimulated insulin secretion dynamics. Furthermore, immunofluorescence and electron microscopy could be used to assess islet architecture, tight junction integrity, and the spatial organization of different endocrine cell types within the islets, revealing the structural impact of [CLDN12](/details-gene/9069) loss. **Therapeutic Potential:** As a transmembrane protein accessible on the cell surface, [CLDN12](/details-gene/9069) presents a viable therapeutic target. Its documented role as a co-receptor for hepatitis C virus suggests that inhibition, for instance via monoclonal antibodies or small molecule inhibitors that block its extracellular loops, could be a strategy for antiviral therapies. Conversely, modulating its function at the blood-brain or blood-CSF barrier could represent a novel strategy to enhance the delivery of therapeutics into the central nervous system for treating neurological disorders.

Genular Protein ID: 2636687943

Symbol: CLD12_HUMAN

Name: Claudin-12

UniProtKB Accession Codes:

P56749 D6W5Q4 Q7LDZ0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 3 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20375010

Title: Claudin association with CD81 defines hepatitis C virus entry.

PubMed ID: 20375010

DOI: 10.1074/jbc.m110.104836

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 244
  • Mass: 27110
  • Checksum: 0547A9D76392CB5F
  • Sequence:
    • MGCRDVHAAT VLSFLCGIAS VAGLFAGTLL PNWRKLRLIT FNRNEKNLTV YTGLWVKCAR 
YDGSSDCLMY DTTWYSSVDQ LDLRVLQFAL PLSMLIAMGA LLLCLIGMCN TAFRSSVPNI 
KLAKCLVNSA GCHLVAGLLF FLAGTVSLSP SIWVIFYNIH LNKKFEPVFS FDYAVYVTIA 
SAGGLFMTSL ILFIWYCTCK SLPSPFWQPL YSHPPSMHTY SQPYSARSRL SAIEIDIPVV 
SHTT

Genular Protein ID: 324531382

Symbol: B2R687_HUMAN

Name: N/A

UniProtKB Accession Codes:

B2R687

Database IDs:

ARBA 8 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 1 PeptideAtlas 1 RefSeq 2 SAM 1

Sequence Information:

  • Length: 244
  • Mass: 27098
  • Checksum: 348AB51A638704B5
  • Sequence:
    • MGCRDVHAAT VLSFLCGIAS VAGLFAGTLL PNWRKLRLIT FNRNEKNLTV YTGLWVKCAR 
YDGSSDCLMY DTTWYSSVDQ LDLRVLQFAL PLSMLIAMGA LLLCLIGMCN TAFRSSVPNI 
KLAKCLVNSA GCHLVAGLLF FLAGTVSLSP SIWVIFYNTH LNKKFEPVFS FDYAVYVTIA 
SAGGLFMTSL ILFIWYCTCK SLPSPFWQPL YSHPPSMHTY SQPYSARSRL SAIEIDIPVV 
SHTT