Details for: VNN1

Gene ID: 8876

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: VNN1

Ensembl ID: ENSG00000112299

Description: vanin 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell CL0000066
    CSI 5.76
    rCSI 8.84%
    PRS 76.79
  • secretory cell CL0000151
    CSI 5.42
    rCSI 5.66%
    PRS 87.1
  • midzonal region hepatocyte CL0019028
    CSI 4.91
    rCSI 11.53%
    PRS 86.46
  • pancreatic ductal cell CL0002079
    CSI 4.6
    rCSI 8.95%
    PRS 89.98
  • Kupffer cell CL0000091
    CSI 4.37
    rCSI 10%
    PRS 89.15
  • goblet cell CL0000160
    CSI 4.35
    rCSI 4.11%
    PRS 86.09
  • glutamatergic neuron CL0000679
    CSI 4.25
    rCSI 8.73%
    PRS 76.16
  • intrahepatic cholangiocyte CL0002538
    CSI 3.97
    rCSI 9.53%
    PRS 89.11
  • epithelial cell of proximal tubule CL0002306
    CSI 3.77
    rCSI 9.22%
    PRS 81.25
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 3.55
    rCSI 8.1%
    PRS 81.35
  • hepatocyte CL0000182
    CSI 3.42
    rCSI 6.13%
    PRS 87.21
  • CD14-positive monocyte CL0001054
    CSI 3.16
    rCSI 3.93%
    PRS 94.31
  • centrilobular region hepatocyte CL0019029
    CSI 3.01
    rCSI 7.86%
    PRS 84.79
  • intestine goblet cell CL0019031
    CSI 2.66
    rCSI 2.36%
    PRS 85.71
  • periportal region hepatocyte CL0019026
    CSI 2.64
    rCSI 10.25%
    PRS 85.77
  • M cell of gut CL0000682
    CSI 2.61
    rCSI 2.78%
    PRS 90.66
  • BEST4+ enteroycte CL4030026
    CSI 2.52
    rCSI 3.14%
    PRS 88.07
  • colonocyte CL1000347
    CSI 2.45
    rCSI 3.51%
    PRS 86.83
  • pancreatic acinar cell CL0002064
    CSI 2.45
    rCSI 3.25%
    PRS 91.63
  • enterocyte CL0000584
    CSI 2.24
    rCSI 3.61%
    PRS 85.36
  • stem cell CL0000034
    CSI 2.02
    rCSI 1.95%
    PRS 83.63
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.77
    rCSI 1.36%
    PRS 91.35
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.7
    rCSI 26.33%
    PRS 91.84
  • neutrophil CL0000775
    CSI 1.56
    rCSI 8.75%
    PRS 86.28
  • Hofbauer cell CL3000001
    CSI 1.52
    rCSI 2.87%
    PRS 93.45
  • intermediate monocyte CL0002393
    CSI 1.39
    rCSI 2.09%
    PRS 92.34
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.35
    rCSI 3.79%
    PRS 91.87

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 [VNN1](/details-gene/8876) (vanin 1) is a protein-coding gene located on chromosome 6q23.2 that encodes a pantetheinase, a GPI-anchored ectoenzyme. This enzyme plays a crucial role in vitamin B5 (pantothenate) metabolism by hydrolyzing pantetheine to produce pantothenic acid and cysteamine ([Link](https://doi.org/10.1016/s0014-5793(99)01439-8)). Functionally, [VNN1](/details-gene/8876) is deeply integrated into both metabolic processes and the innate immune system, particularly in the context of inflammation and oxidative stress response ([Link](https://doi.org/10.1107/s1399004714022767)). **Overall**, its expression is most significant in various types of [epithelial cell](/details-cell/CL0000066) and [secretory cell](/details-cell/CL0000151), with particularly high CSI values observed in liver cells such as [midzonal region hepatocyte](/details-cell/CL0019028) and [Kupffer cell](/details-cell/CL0000091), suggesting a key function in metabolically active and immunologically engaged tissues. ## Cellular Roles and Expression Landscape The expression profile of [VNN1](/details-gene/8876) highlights its prominent role in epithelial and secretory tissues responsible for metabolic regulation and barrier functions. **Overall**, the gene shows the highest significance in [epithelial cell](/details-cell/CL0000066) (CSI: 5.76) and [secretory cell](/details-cell/CL0000151) (CSI: 5.42). This pattern is further specified in various organ systems, with high CSI scores in liver cells including [midzonal region hepatocyte](/details-cell/CL0019028), [Kupffer cell](/details-cell/CL0000091), [intrahepatic cholangiocyte](/details-cell/CL0002538), and other [hepatocyte](/details-cell/CL0000182) subtypes. This hepatic signature suggests a vital role in liver metabolism and local immune surveillance. Beyond the liver, [VNN1](/details-gene/8876) is a significant marker in other secretory and barrier tissues, including [pancreatic ductal cell](/details-cell/CL0002079) (CSI: 4.60), [goblet cell](/details-cell/CL0000160) (CSI: 4.35), [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 3.77), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 3.55). Its expression in immune cells like [Kupffer cell](/details-cell/CL0000091) and [CD14-positive monocyte](/details-cell/CL0001054) is consistent with its established function in the inflammatory response. The notable, though slightly lower, CSI score in [glutamatergic neuron](/details-cell/CL0000679) (CSI: 4.25) suggests a potential, less-characterized role in the central nervous system. The general absence of high significance in lymphoid cell lineages (T cells, B cells) indicates a specialized function predominantly within the myeloid and epithelial compartments. ## Pathways and Molecular Function The primary molecular function of [VNN1](/details-gene/8876) is its pantetheine hydrolase activity ([GO:0017159](https://www.ebi.ac.uk/QuickGO/term/GO:0017159)), which is a key step in the vitamin B5 (pantothenate) metabolism pathway ([R-HSA-199220](https://reactome.org/content/detail/R-HSA-199220)) and coenzyme A catabolism ([GO:0015938](https://www.ebi.ac.uk/QuickGO/term/GO:0015938)). This metabolic role is intrinsically linked to its function in the immune system. [VNN1](/details-gene/8876) is an annotated participant in the [immune system](/details-pathway/R-HSA-168256), specifically the [innate immune system](/details-pathway/R-HSA-168249) ([GO:0045087](https://www.ebi.ac.uk/QuickGO/term/GO:0045087)). Its involvement in both acute ([GO:0002526](https://www.ebi.ac.uk/QuickGO/term/GO:0002526)) and chronic ([GO:0002544](https://www.ebi.ac.uk/QuickGO/term/GO:0002544)) inflammatory responses underscores its importance in modulating immunity. This is further supported by its role in processes like [neutrophil degranulation](/details-pathway/R-HSA-6798695) and its localization to the [azurophil granule membrane](/details-component/GO:0035577). The enzyme's activity also connects to cellular stress, as it is involved in the response to oxidative stress ([GO:0006979](https://www.ebi.ac.uk/QuickGO/term/GO:0006979)) and the positive regulation of apoptosis ([GO:1902177](https://www.ebi.ac.uk/QuickGO/term/GO:1902177)). As a GPI-anchored protein located on the [plasma membrane](/details-component/GO:0005886), [VNN1](/details-gene/8876) is well-positioned to sense and respond to extracellular signals in its microenvironment. ## Research Directions The dual role of [VNN1](/details-gene/8876) at the interface of metabolism and inflammation makes it a compelling subject for further investigation, particularly in the context of metabolic and inflammatory diseases. Its high expression in epithelial barriers and metabolically active tissues suggests its dysregulation could contribute to pathology in organs like the liver, pancreas, and gut. Based on its known functions and expression patterns, several testable hypotheses can be proposed: 1. In conditions of metabolic stress like non-alcoholic steatohepatitis (NASH), the pantetheinase activity of [VNN1](/details-gene/8876) in [hepatocyte](/details-cell/CL0000182) and [Kupffer cell](/details-cell/CL0000091) may be a critical regulator of the local inflammatory response by modulating cysteamine levels, a known antioxidant, thereby protecting against oxidative damage. 2. Given its high expression in [goblet cell](/details-cell/CL0000160) and its role in inflammation, [VNN1](/details-gene/8876) could regulate intestinal barrier function during inflammatory bowel disease (IBD) by influencing mucus production or epithelial cell adhesion. To test the first hypothesis, a compelling experimental approach would be to use a murine model of diet-induced NASH with a liver-specific knockout of [VNN1](/details-gene/8876). The progression of liver fibrosis, inflammation (histology and cytokine profiling), lipid accumulation (Oil Red O staining), and markers of oxidative stress (e.g., glutathione levels) could be compared between knockout and wild-type animals. This would directly assess the in vivo contribution of hepatic [VNN1](/details-gene/8876) to the pathophysiology of NASH. As a therapeutic target, [VNN1](/details-gene/8876) presents an intriguing profile. Because it is an ectoenzyme located on the cell surface, it is highly accessible to small molecule inhibitors or therapeutic antibodies. In chronic inflammatory diseases, inhibition of [VNN1](/details-gene/8876) could be a viable strategy to dampen excessive inflammation. However, its protective role in oxidative stress suggests that systemic inhibition could have unintended consequences. Therefore, a targeted delivery system or the development of context-specific modulators might be necessary to harness its therapeutic potential effectively.

Genular Protein ID: 1187008361

Symbol: VNN1_HUMAN

Name: Pantetheinase

UniProtKB Accession Codes:

O95497 A8K310 Q4JFW6 Q4VAS7 Q4VAS8 Q4VAS9 Q9UF16 Q9UJF4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 9 Ensembl 1 EvolutionaryTrace 1 GO 16 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 Rhea 1 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9790769

Title: Two human genes related to murine vanin-1 are located on the long arm of human chromosome 6.

PubMed ID: 9790769

DOI: 10.1006/geno.1998.5481

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 10567687

Title: Is pantetheinase the actual identity of mouse and human vanin-1 proteins?

PubMed ID: 10567687

DOI: 10.1016/s0014-5793(99)01439-8

PubMed ID: 11491533

Title: Vanin genes are clustered (human 6q22-24 and mouse 10A2B1) and encode isoforms of pantetheinase ectoenzymes.

PubMed ID: 11491533

DOI: 10.1007/s002510100327

PubMed ID: 15084671

Title: A proteomic analysis of human bile.

PubMed ID: 15084671

DOI: 10.1074/mcp.m400015-mcp200

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 19322213

Title: Expression of the vanin gene family in normal and inflamed human skin: induction by proinflammatory cytokines.

PubMed ID: 19322213

DOI: 10.1038/jid.2009.67

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 25478849

Title: The structure of vanin 1: a key enzyme linking metabolic disease and inflammation.

PubMed ID: 25478849

DOI: 10.1107/s1399004714022767

Sequence Information:

  • Length: 513
  • Mass: 57012
  • Checksum: 018D2417C12E403F
  • Sequence:
    • MTTQLPAYVA ILLFYVSRAS CQDTFTAAVY EHAAILPNAT LTPVSREEAL ALMNRNLDIL 
EGAITSAADQ GAHIIVTPED AIYGWNFNRD SLYPYLEDIP DPEVNWIPCN NRNRFGQTPV 
QERLSCLAKN NSIYVVANIG DKKPCDTSDP QCPPDGRYQY NTDVVFDSQG KLVARYHKQN 
LFMGENQFNV PKEPEIVTFN TTFGSFGIFT CFDILFHDPA VTLVKDFHVD TIVFPTAWMN 
VLPHLSAVEF HSAWAMGMRV NFLASNIHYP SKKMTGSGIY APNSSRAFHY DMKTEEGKLL 
LSQLDSHPSH SAVVNWTSYA SSIEALSSGN KEFKGTVFFD EFTFVKLTGV AGNYTVCQKD 
LCCHLSYKMS ENIPNEVYAL GAFDGLHTVE GRYYLQICTL LKCKTTNLNT CGDSAETAST 
RFEMFSLSGT FGTQYVFPEV LLSENQLAPG EFQVSTDGRL FSLKPTSGPV LTVTLFGRLY 
EKDWASNASS GLTAQARIIM LIVIAPIVCS LSW