Details for: CGNL1

Gene ID: 84952

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: CGNL1

Ensembl ID: ENSG00000128849

Description: cingulin like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • cerebral cortex endothelial cell CL1001602
    CSI 27.1
    rCSI 46.87%
    PRS 51.28
  • renal beta-intercalated cell CL0002201
    CSI 12.53
    rCSI 29.88%
    PRS 62.25
  • mononuclear phagocyte CL0000113
    CSI 11.38
    rCSI 25.04%
    PRS 65.41
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 10.6
    rCSI 27.41%
    PRS 56.1
  • hepatocyte CL0000182
    CSI 9.6
    rCSI 17.19%
    PRS 60.27
  • parietal epithelial cell CL1000452
    CSI 7.73
    rCSI 20.66%
    PRS 52.22
  • renal alpha-intercalated cell CL0005011
    CSI 7.43
    rCSI 9.93%
    PRS 69.96
  • Mueller cell CL0000636
    CSI 6.93
    rCSI 15.81%
    PRS 52.98
  • lung neuroendocrine cell CL1000223
    CSI 6.06
    rCSI 8.97%
    PRS 66.42
  • acinar cell CL0000622
    CSI 6.03
    rCSI 8.85%
    PRS 72.7
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 6.01
    rCSI 27.59%
    PRS 72.37
  • endocardial cell CL0002350
    CSI 5.93
    rCSI 28.39%
    PRS 59.94
  • hepatic stellate cell CL0000632
    CSI 5.67
    rCSI 21.25%
    PRS 53.25
  • renal principal cell CL0005009
    CSI 5.6
    rCSI 14.56%
    PRS 64.68
  • astrocyte of the cerebral cortex CL0002605
    CSI 5.54
    rCSI 12.41%
    PRS 43.65
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 5.49
    rCSI 7.78%
    PRS 57.38
  • retinal blood vessel endothelial cell CL0002585
    CSI 5.39
    rCSI 8.6%
    PRS 65.41
  • epithelial cell of proximal tubule CL0002306
    CSI 5.38
    rCSI 13.14%
    PRS 54.77
  • Schwann cell CL0002573
    CSI 5.25
    rCSI 14.93%
    PRS 59.34
  • lung secretory cell CL1000272
    CSI 5.23
    rCSI 12.95%
    PRS 59.53
  • podocyte CL0000653
    CSI 5.23
    rCSI 23.24%
    PRS 60.58
  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.04
    rCSI 3.91%
    PRS 62.89
  • luminal cell of prostate epithelium CL0002340
    CSI 4.89
    rCSI 26.32%
    PRS 73.5
  • skin fibroblast CL0002620
    CSI 4.82
    rCSI 4.15%
    PRS 66.71
  • melanocyte CL0000148
    CSI 4.48
    rCSI 3.32%
    PRS 53.77
  • ionocyte CL0005006
    CSI 4.46
    rCSI 4.78%
    PRS 60.45
  • adipocyte CL0000136
    CSI 4.41
    rCSI 5.66%
    PRS 53.87
  • pulmonary ionocyte CL0017000
    CSI 4.4
    rCSI 5.35%
    PRS 68.57
  • fibroblast of cardiac tissue CL0002548
    CSI 4.33
    rCSI 20.74%
    PRS 61.34
  • epithelial cell of lung CL0000082
    CSI 4.29
    rCSI 3.55%
    PRS 60.21
  • myoepithelial cell CL0000185
    CSI 4.27
    rCSI 10.8%
    PRS 69.13
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.24
    rCSI 10.75%
    PRS 50.56
  • endothelial cell of vascular tree CL0002139
    CSI 4.05
    rCSI 22.15%
    PRS 60.32
  • periportal region hepatocyte CL0019026
    CSI 3.95
    rCSI 15.36%
    PRS 66.23
  • midzonal region hepatocyte CL0019028
    CSI 3.93
    rCSI 9.23%
    PRS 66.09
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.75
    rCSI 11.13%
    PRS 71.09
  • adventitial cell CL0002503
    CSI 3.75
    rCSI 8.95%
    PRS 69.82
  • kidney collecting duct intercalated cell CL1001432
    CSI 3.7
    rCSI 26.4%
    PRS 61.57
  • retinal pigment epithelial cell CL0002586
    CSI 3.63
    rCSI 7.22%
    PRS 58.92
  • renal interstitial pericyte CL1001318
    CSI 3.62
    rCSI 9.98%
    PRS 56.89
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.38
    rCSI 8.81%
    PRS 60.98
  • fibroblast of lung CL0002553
    CSI 3.3
    rCSI 3.07%
    PRS 61.71
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.22
    rCSI 20.09%
    PRS 53.03
  • pulmonary alveolar type 2 cell CL0002063
    CSI 3.16
    rCSI 4.9%
    PRS 68.76
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 3.12
    rCSI 26.92%
    PRS 58.66
  • mucus secreting cell CL0000319
    CSI 2.88
    rCSI 4.57%
    PRS 72.25
  • cardiac muscle cell CL0000746
    CSI 2.78
    rCSI 3.98%
    PRS 50.89
  • centrilobular region hepatocyte CL0019029
    CSI 2.58
    rCSI 6.72%
    PRS 65.03
  • intestinal tuft cell CL0019032
    CSI 2.54
    rCSI 3.89%
    PRS 65.34
  • choroid plexus epithelial cell CL0000706
    CSI 2.46
    rCSI 4.03%
    PRS 50.41
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 2.45
    rCSI 25.93%
    PRS 59.54
  • squamous epithelial cell CL0000076
    CSI 2.4
    rCSI 5.71%
    PRS 64.93
  • pulmonary alveolar type 1 cell CL0002062
    CSI 2.3
    rCSI 13.27%
    PRS 59.82
  • macula densa epithelial cell CL1000850
    CSI 2.3
    rCSI 32.99%
    PRS 77.19
  • mesothelial cell CL0000077
    CSI 2.27
    rCSI 8.88%
    PRS 37.87
  • duct epithelial cell CL0000068
    CSI 2.26
    rCSI 3.31%
    PRS 65.66
  • stem cell CL0000034
    CSI 2.26
    rCSI 2.18%
    PRS 51.67
  • intrahepatic cholangiocyte CL0002538
    CSI 2.13
    rCSI 5.11%
    PRS 71.65
  • brush cell CL0002204
    CSI 2.1
    rCSI 4.16%
    PRS 78.06
  • serous secreting cell CL0000313
    CSI 1.88
    rCSI 9.5%
    PRS 85.24
  • chondrocyte CL0000138
    CSI 1.86
    rCSI 2.96%
    PRS 53.47
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 1.85
    rCSI 19.62%
    PRS 66.67
  • acinar cell of salivary gland CL0002623
    CSI 1.74
    rCSI 40.6%
    PRS 80.19
  • endothelial cell of placenta CL0009092
    CSI 1.66
    rCSI 8.17%
    PRS 72.35
  • alveolar adventitial fibroblast CL4028006
    CSI 1.65
    rCSI 2.6%
    PRS 63.46
  • tuft cell of colon CL0009041
    CSI 1.49
    rCSI 3.48%
    PRS 73.53
  • pancreatic acinar cell CL0002064
    CSI 1.49
    rCSI 1.98%
    PRS 67.59
  • neuroendocrine cell CL0000165
    CSI 1.43
    rCSI 5.54%
    PRS 75.73
  • mesodermal cell CL0000222
    CSI 1.33
    rCSI 1.6%
    PRS 59.05
  • glial cell CL0000125
    CSI 1.05
    rCSI 4%
    PRS 52.04
  • endothelial cell of uterus CL0009095
    CSI 1.04
    rCSI 7.59%
    PRS 77.86
  • pancreatic ductal cell CL0002079
    CSI 0.84
    rCSI 1.63%
    PRS 64.04
  • bronchiolar smooth muscle cell CL4033017
    CSI 0.48
    rCSI 7.22%
    PRS 77.77
  • vasa recta descending limb cell CL1001285
    CSI 0.44
    rCSI 3.55%
    PRS 80
  • mesenchymal cell CL0008019
    CSI 0.33
    rCSI 0.84%
    PRS 55.34
  • peptic cell CL0000155
    CSI 0.28
    rCSI 2.73%
    PRS 79.73

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.

Comma-separated if multiple.
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 [CGNL1](/details-gene/84952), or Cingulin-like protein 1, is a protein-coding gene located on chromosome 15q21.3. Functionally, it is implicated in the organization of the actin cytoskeleton and the formation and maintenance of bicellular tight junctions. Its expression profile indicates a significant role in cells that form critical physiological barriers. **Overall**, [CGNL1](/details-gene/84952) shows the highest significance in [cerebral cortex endothelial cells](/details-cell/CL1001602), as well as in various specialized epithelial cells of the kidney and liver, suggesting it is a key structural or regulatory component in tissues requiring tight cellular adhesion and controlled permeability. The characterization of this gene has been supported by large-scale cDNA sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504), [Link](https://doi.org/10.1093/dnares/7.6.347)). ## Cellular Roles and Expression Landscape The expression pattern of [CGNL1](/details-gene/84952) strongly points to a primary function in maintaining the integrity and function of endothelial and epithelial layers. **Overall**, its most significant expression is observed in [cerebral cortex endothelial cells](/details-cell/CL1001602) (CSI: 27.10), which are the primary constituents of the blood-brain barrier. This is complemented by high significance in several specialized renal epithelial cells, including [renal beta-intercalated cells](/details-cell/CL0002201) (CSI: 12.53), [kidney loop of Henle thin ascending limb epithelial cells](/details-cell/CL1001107) (CSI: 10.60), and [renal alpha-intercalated cells](/details-cell/CL0005011) (CSI: 7.43), all of which are involved in selective transport and barrier functions within the nephron. Furthermore, high significance in [hepatocytes](/details-cell/CL0000182) (CSI: 9.60) and [endothelial cells of periportal hepatic sinusoids](/details-cell/CL0019021) (CSI: 6.01) highlights its importance in the liver, another organ dependent on tight cellular organization for metabolic function and blood filtration. The notable expression in [mononuclear phagocytes](/details-cell/CL0000113) (CSI: 11.38) suggests a potential secondary role in immune cells, possibly related to cell migration or adhesion. Collectively, the data indicates that [CGNL1](/details-gene/84952) is a key component in a diverse set of cells defined by their requirement for robust and regulated cell-cell junctions. ## Pathways and Molecular Function The functional annotations for [CGNL1](/details-gene/84952) are highly consistent with its observed cellular expression profile. The gene product is a known component of the [bicellular tight junction](/details-go/GO:0005923), providing a direct molecular basis for its high significance in barrier-forming endothelial and epithelial cells. Its involvement in [actin filament organization](/details-go/GO:0007015) and the [negative regulation of stress fiber assembly](/details-go/GO:0051497) suggests it plays a crucial role in modulating the cytoskeleton to support and regulate the stability of these junctions. Mechanistically, this may be achieved through its role in the [negative regulation of small gtpase mediated signal transduction](/details-go/GO:0051058), as small GTPases like Rho and Rac are central regulators of cytoskeletal dynamics and cell adhesion. By localizing to cell-cell junctions ([GO:0150105](https://www.ebi.ac.uk/QuickGO/term/GO:0150105)) and binding to other proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)), [CGNL1](/details-gene/84952) likely acts as a scaffold or regulatory protein that integrates signaling pathways with the physical architecture of the cell junction. ## Research Directions The specific and high expression of [CGNL1](/details-gene/84952) in cells forming critical physiological barriers, combined with its known function in tight junction biology, presents several avenues for future research. **Proposed Hypotheses:** 1. Given its top-ranking significance in [cerebral cortex endothelial cells](/details-cell/CL1001602), [CGNL1](/details-gene/84952) is essential for the formation and maintenance of the blood-brain barrier (BBB), and its disruption leads to increased paracellular permeability. 2. Based on its high expression in multiple renal tubular cell types, [CGNL1](/details-gene/84952) plays a specialized role in regulating the dynamic cytoskeletal rearrangements required for efficient ion and water transport across the kidney epithelium. Its dysfunction may contribute to renal transport disorders. 3. The significant expression in [mononuclear phagocytes](/details-cell/CL0000113) suggests that [CGNL1](/details-gene/84952) may regulate adhesive properties or motility of these immune cells, potentially influencing their ability to extravasate from the bloodstream into tissues. **Key Experimental Approach:** To test the hypothesis regarding the role of [CGNL1](/details-gene/84952) in BBB integrity, a combination of in vitro and in vivo models could be employed. Initially, one could use an in vitro model consisting of human cerebral microvascular endothelial cells (hCMECs) grown in a transwell system. CRISPR-Cas9-mediated knockout or siRNA-mediated knockdown of [CGNL1](/details-gene/84952) could be performed in these cells. Barrier function would be assessed by measuring transendothelial electrical resistance (TEER) and quantifying the flux of fluorescently-labeled dextrans of various molecular weights across the cell monolayer. A significant decrease in TEER and an increase in dextran permeability in knockout/knockdown cells would support the hypothesis. **Therapeutic Potential:** As a structural and regulatory component of tight junctions in essential organs like the brain, kidney, and liver, [CGNL1](/details-gene/84952) presents a challenging therapeutic target. Systemic inhibition could lead to severe side effects by compromising barrier integrity throughout the body. However, if [CGNL1](/details-gene/84952) is found to be aberrantly overexpressed or mislocalized in pathologies characterized by excessive barrier formation (e.g., fibrosis) or in tumor angiogenesis, it could become a target for highly localized inhibition. Conversely, therapeutic activation or targeted delivery of [CGNL1](/details-gene/84952) could be explored in conditions involving pathological barrier breakdown, such as in certain neuroinflammatory diseases or sepsis.

Genular Protein ID: 1482493954

Symbol: CGNL1_HUMAN

Name: Cingulin-like protein 1

UniProtKB Accession Codes:

Q0VF96 Q05BZ4 Q52LR0 Q695C7 Q7Z2L3 Q96JV2 Q96MN6 Q9C0B4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 1 GO 7 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 3 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 11214970

Title: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 11214970

DOI: 10.1093/dnares/7.6.347

PubMed ID: 12736278

Title: Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene.

PubMed ID: 12736278

DOI: 10.1056/nejmoa021559

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 22891260

Title: Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex.

PubMed ID: 22891260

DOI: 10.1083/jcb.201202094

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 1302
  • Mass: 149079
  • Checksum: E41B55B5B50D2A28
  • Sequence:
    • MELYFGEYQH VQQEYGVHLR LASDDTQKSR SSQNSKAGSY GVSIRVQGID GHPYIVLNNT 
ERCLAGTSFS ENGPPFPPPV INNLPLHSSN GSVPKENSEE LQLPENPYAQ PSPIRNLKQP 
LLHEGKNGVL DRKDGSVKPS HLLNFQRHPE LLQPYDPEKN ELNLQNHQPS ESNWLKTLTE 
EGINNKKPWT CFPKPSNSQP TSPSLEDPAK SGVTAIRLCS SVVIEDPKKQ TSVCVNVQSC 
TKERVGEEAL FTSGRPLTAH SPHAHPETKK TRPDVLPFRR QDSAGPVLDG ARSRRSSSSS 
TTPTSANSLY RFLLDDQECA IHADNVNRHE NRRYIPFLPG TGRDIDTGSI PGVDQLIEKF 
DQKPGLQRRG RSGKRNRINT DDRKRSRSVD SAFPFGLQGN SEYLIEFSRN LGKSSEHLLR 
PSQVCPQRPL SQERRGKQSV GRTFAKLQGA AHGASCAHSR PPQPNIDGKV LETEGSQEST 
VIRAPSLGAQ SKKEEEVKTA TATLMLQNRA TATSPDSGAK KISVKTFPSA SNTQATPDLL 
KGQQELTQQT NEETAKQILY NYLKEGSTDN DDATKRKVNL VFEKIQTLKS RAAGSAQGNN 
QACNSTSEVK DLLEQKSKLT IEVAELQRQL QLEVKNQQNI KEERERMRAN LEELRSQHNE 
KVEENSTLQQ RLEESEGELR KNLEELFQVK MEREQHQTEI RDLQDQLSEM HDELDSAKRS 
EDREKGALIE ELLQAKQDLQ DLLIAKEEQE DLLRKREREL TALKGALKEE VSSHDQEMDK 
LKEQYDAELQ ALRESVEEAT KNVEVLASRS NTSEQDQAGT EMRVKLLQEE NEKLQGRSEE 
LERRVAQLQR QIEDLKGDEA KAKETLKKYE GEIRQLEEAL VHARKEEKEA VSARRALENE 
LEAAQGNLSQ TTQEQKQLSE KLKEESEQKE QLRRLKNEME NERWHLGKTI EKLQKEMADI 
VEASRTSTLE LQNQLDEYKE KNRRELAEMQ RQLKEKTLEA EKSRLTAMKM QDEMRLMEEE 
LRDYQRAQDE ALTKRQLLEQ TLKDLEYELE AKSHLKDDRS RLVKQMEDKV SQLEMELEEE 
RNNSDLLSER ISRSREQMEQ LRNELLQERA ARQDLECDKI SLERQNKDLK SRIIHLEGSY 
RSSKEGLVVQ MEARIAELED RLESEERDRA NLQLSNRRLE RKVKELVMQV DDEHLSLTDQ 
KDQLSLRLKA MKRQVEEAEE EIDRLESSKK KLQRELEEQM DMNEHLQGQL NSMKKDLRLK 
KLPSKVLDDM DDDDDLSTDG GSLYEAPVSY TFSKDSTVAS QI