Details for: VTCN1

Gene ID: 79679

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: VTCN1

Ensembl ID: ENSG00000134258

Description: V-set domain containing T cell activation inhibitor 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.59
    rCSI 4.33%
    PRS 99.07
  • pancreatic ductal cell CL0002079
    CSI 5.57
    rCSI 10.84%
    PRS 98.1
  • epithelial cell CL0000066
    CSI 4.54
    rCSI 6.97%
    PRS 92.64
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.66
    rCSI 3.52%
    PRS 97.63
  • acinar cell CL0000622
    CSI 3.57
    rCSI 5.23%
    PRS 99.06
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 3.49
    rCSI 4.95%
    PRS 97.79
  • luminal epithelial cell of mammary gland CL0002326
    CSI 3.48
    rCSI 6.33%
    PRS 98.88
  • secretory cell CL0000151
    CSI 3.48
    rCSI 3.63%
    PRS 97.92
  • duct epithelial cell CL0000068
    CSI 3.42
    rCSI 5%
    PRS 99.18
  • conjunctival epithelial cell CL1000432
    CSI 3.25
    rCSI 4.96%
    PRS 97.51
  • cholangiocyte CL1000488
    CSI 3.19
    rCSI 19.11%
    PRS 96.81
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3.16
    rCSI 8.17%
    PRS 97.6
  • nasal mucosa goblet cell CL0002480
    CSI 3.16
    rCSI 3.66%
    PRS 97.55
  • lung secretory cell CL1000272
    CSI 3.14
    rCSI 7.78%
    PRS 98.97
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.86
    rCSI 7.25%
    PRS 96.67
  • glandular epithelial cell CL0000150
    CSI 2.11
    rCSI 5.55%
    PRS 99.48
  • mammary gland epithelial cell CL0002327
    CSI 1.64
    rCSI 5.77%
    PRS 98.9
  • basal cell of epithelium of trachea CL1000348
    CSI 0.7
    rCSI 4.94%
    PRS 97.97
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.36
    rCSI 3.82%
    PRS 96.48

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 [VTCN1](/details-gene/79679), also known as V-set domain containing T cell activation inhibitor 1 or B7-H4, is a protein-coding gene located on chromosome 1. As a member of the B7 family of immune co-stimulatory/co-inhibitory molecules, [VTCN1](/details-gene/79679) functions as a key negative regulator of T-cell immunity [Link](https://doi.org/10.1016/s1074-7613(03)00152-3). It is primarily expressed on the cell surface and is involved in pathways such as the [adaptive immune response](/details-go/GO:0002250) and [negative regulation of T cell activation](/details-go/GO:0050868). **Overall**, expression data reveals its high significance in a wide array of epithelial cell types, particularly those with secretory or barrier functions, suggesting a role in maintaining immune homeostasis at mucosal and glandular sites. Its overexpression has been documented in several cancers, implicating it in tumor immune evasion [Link](https://doi.org/10.1016/j.lungcan.2006.05.012), [Link](https://doi.org/10.1016/j.yexcr.2005.01.018). ## Cellular Roles and Expression Landscape The expression profile of [VTCN1](/details-gene/79679) highlights its prominent role in epithelial biology. **Overall**, the gene shows the highest significance in secretory and barrier epithelial lineages across multiple organ systems. Top-ranked cell types include `[epithelial cell of lower respiratory tract](/details-cell/CL0002632)` (CSI: 5.59) and `[pancreatic ductal cell](/details-cell/CL0002079)` (CSI: 5.57), underscoring its importance in these glandular and mucosal tissues. This pattern of high expression extends to other specialized epithelial cells, such as `[fallopian tube secretory epithelial cell](/details-cell/CL4030006)`, `[luminal epithelial cell of mammary gland](/details-cell/CL0002326)`, and various `[kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111)`. The consistent high significance in `[epithelial cell](/details-cell/CL0000066)` (CSI: 4.54), `[secretory cell](/details-cell/CL0000151)` (CSI: 3.48), and `[duct epithelial cell](/details-cell/CL0000068)` (CSI: 3.42) suggests that [VTCN1](/details-gene/79679) is a key molecular feature of epithelial tissues responsible for forming ducts and secreting substances. This widespread epithelial expression is consistent with a role in modulating local immune responses at interfaces between the body and the external environment or at sites of active secretion. ## Pathways and Molecular Function Functional annotations for [VTCN1](/details-gene/79679) confirm its role as an immunomodulatory protein located on the `[external side of plasma membrane](/details-go/GO:0009897)`. Its primary biological function is the inhibition of T-cell responses, as detailed by its association with processes like [negative regulation of t cell activation](/details-go/GO:0050868) and [negative regulation of t cell proliferation](/details-go/GO:0042130). This inhibitory activity is central to its function in the [adaptive immune response](/details-go/GO:0002250) and its involvement in the [T cell receptor signaling pathway](/details-go/GO:0050852) [Link](https://doi.org/10.1073/pnas.1434299100). Interestingly, while its predominant role is inhibitory, [VTCN1](/details-gene/79679) is also annotated with [positive regulation of interleukin-2 production](/details-go/GO:0032743) and [positive regulation of t cell proliferation](/details-go/GO:0042102), suggesting a more complex, context-dependent regulatory function. Its expression on epithelial cells, coupled with its role in T-cell regulation, indicates that it may act as a crucial checkpoint molecule that prevents excessive T-cell-mediated inflammation and damage to sensitive barrier tissues. ## Research Directions The established role of [VTCN1](/details-gene/79679) as a T-cell inhibitor, combined with its overexpression in various cancers such as ovarian, breast, and lung carcinoma, points to its significant involvement in pathological immune evasion [Link](https://doi.org/10.1158/0008-5472.can-07-1866), [Link](https://doi.org/10.1016/j.yexcr.2005.01.018). This presents clear avenues for future research into both fundamental immunology and clinical oncology. **Proposed Hypotheses:** 1. Given its high expression in respiratory and other mucosal epithelial cells, the expression of [VTCN1](/details-gene/79679) at these barrier sites is likely dynamically regulated by the local cytokine milieu. Specifically, its upregulation may be a key mechanism for resolving inflammation and restoring immune homeostasis following infection or injury, potentially induced by anti-inflammatory cytokines like IL-10, as has been suggested on APCs [Link](https://doi.org/10.4049/jimmunol.177.1.40). 2. The aberrant overexpression of [VTCN1](/details-gene/79679) in epithelial-derived cancers is a primary driver of immune escape. This process may be initiated by oncogenic signaling pathways that co-opt its normal physiological function, creating an immunosuppressive tumor microenvironment that directly inhibits the activity of tumor-infiltrating T lymphocytes. **Experimental Approach:** To test the first hypothesis, primary human bronchial epithelial cells could be cultured in an air-liquid interface (ALI) model to achieve differentiation. These cultures could then be stimulated with a panel of pro-inflammatory (e.g., TNF-α, IFN-γ) and anti-inflammatory (e.g., IL-10, TGF-β) cytokines. Changes in [VTCN1](/details-gene/79679) mRNA and surface protein expression could be quantified using qRT-PCR and flow cytometry, respectively. A functional readout could be achieved by co-culturing the stimulated epithelial cells with pre-activated autologous CD8+ T-cells and measuring T-cell proliferation (e.g., via CFSE dilution) and effector function (e.g., IFN-γ production by ELISA). **Therapeutic Potential:** [VTCN1](/details-gene/79679) represents a highly promising therapeutic target for cancer immunotherapy. As a cell-surface protein that acts as an immune checkpoint, it is amenable to targeting by monoclonal antibodies. An inhibitory antibody that blocks the interaction of [VTCN1](/details-gene/79679) on tumor cells with its cognate receptor on T-cells could reverse its immunosuppressive effects, thereby restoring anti-tumor T-cell activity. Such a strategy would be analogous to existing checkpoint inhibitors targeting the PD-1/PD-L1 axis, making the inhibition of [VTCN1](/details-gene/79679) a compelling approach for treating a variety of solid tumors, particularly those of epithelial origin.

Genular Protein ID: 2111009791

Symbol: VTCN1_HUMAN

Name: V-set domain-containing T-cell activation inhibitor 1

UniProtKB Accession Codes:

Q7Z7D3 Q0GN76 Q45VN0 Q5WPZ3 Q6P097 Q9H6B2

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CPTAC 1 CPTC 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12818165

Title: B7-H4, a molecule of the B7 family, negatively regulates T cell immunity.

PubMed ID: 12818165

DOI: 10.1016/s1074-7613(03)00152-3

PubMed ID: 12920180

Title: B7x: a widely expressed B7 family member that inhibits T cell activation.

PubMed ID: 12920180

DOI: 10.1073/pnas.1434299100

PubMed ID: 16782226

Title: B7-H3 and B7-H4 expression in non-small-cell lung cancer.

PubMed ID: 16782226

DOI: 10.1016/j.lungcan.2006.05.012

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 14568939

Title: Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family.

PubMed ID: 14568939

DOI: 10.4049/jimmunol.171.9.4650

PubMed ID: 15878339

Title: The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation.

PubMed ID: 15878339

DOI: 10.1016/j.yexcr.2005.01.018

PubMed ID: 16606666

Title: B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.

PubMed ID: 16606666

DOI: 10.1084/jem.20050930

PubMed ID: 16785496

Title: Induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells.

PubMed ID: 16785496

DOI: 10.4049/jimmunol.177.1.40

PubMed ID: 16798883

Title: B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival.

PubMed ID: 16798883

DOI: 10.1073/pnas.0600937103

PubMed ID: 17875732

Title: Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma.

PubMed ID: 17875732

DOI: 10.1158/0008-5472.can-07-1866

PubMed ID: 17509674

Title: B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration.

PubMed ID: 17509674

DOI: 10.1016/j.ygyno.2007.03.039

Sequence Information:

  • Length: 282
  • Mass: 30878
  • Checksum: 1C9C565A9242E78C
  • Sequence:
    • MASLGQILFW SIISIIIILA GAIALIIGFG ISGRHSITVT TVASAGNIGE DGILSCTFEP 
DIKLSDIVIQ WLKEGVLGLV HEFKEGKDEL SEQDEMFRGR TAVFADQVIV GNASLRLKNV 
QLTDAGTYKC YIITSKGKGN ANLEYKTGAF SMPEVNVDYN ASSETLRCEA PRWFPQPTVV 
WASQVDQGAN FSEVSNTSFE LNSENVTMKV VSVLYNVTIN NTYSCMIEND IAKATGDIKV 
TESEIKRRSH LQLLNSKASL CVSSFFAISW ALLPLSPYLM LK