Details for: VEPH1

Gene ID: 79674

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: VEPH1

Ensembl ID: ENSG00000197415

Description: ventricular zone expressed PH domain containing 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Negative regulation of smad protein signal transduction
    (GO:0060392)
  • Negative regulation of transforming growth factor beta receptor signaling pathway
    (GO:0030512)
  • Phosphatidylinositol-5-phosphate binding
    (GO:0010314)
  • Plasma membrane
    (GO:0005886)
  • Protein binding
    (GO:0005515)
  • Regulation of signal transduction
    (GO:0009966)

Significant Cells

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

  • sncg GABAergic cortical interneuron CL4023015
    CSI 7.24
    rCSI 11.64%
    PRS 92.43
  • melanocyte CL0000148
    CSI 5.09
    rCSI 3.77%
    PRS 95.89
  • epithelial cell of lung CL0000082
    CSI 4.81
    rCSI 3.99%
    PRS 98.04
  • epithelial cell of proximal tubule CL0002306
    CSI 4.11
    rCSI 10.03%
    PRS 93.74
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.8
    rCSI 9.63%
    PRS 95.08
  • lung ciliated cell CL1000271
    CSI 3.5
    rCSI 4.04%
    PRS 94.72
  • adipocyte CL0000136
    CSI 3.29
    rCSI 4.22%
    PRS 93.42
  • ionocyte CL0005006
    CSI 3.24
    rCSI 3.47%
    PRS 97.74
  • blood vessel endothelial cell CL0000071
    CSI 3.19
    rCSI 6.63%
    PRS 96.56
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.19
    rCSI 2.47%
    PRS 98.5
  • intrahepatic cholangiocyte CL0002538
    CSI 3.14
    rCSI 7.53%
    PRS 96.93
  • choroid plexus epithelial cell CL0000706
    CSI 3.14
    rCSI 5.14%
    PRS 94.57
  • renal beta-intercalated cell CL0002201
    CSI 2.67
    rCSI 6.35%
    PRS 97.09
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.64
    rCSI 3.75%
    PRS 96.56
  • lung secretory cell CL1000272
    CSI 2.6
    rCSI 6.44%
    PRS 98.16
  • renal principal cell CL0005009
    CSI 2.57
    rCSI 6.67%
    PRS 96.95
  • ependymal cell CL0000065
    CSI 2.44
    rCSI 4.95%
    PRS 87.8
  • radial glial cell CL0000681
    CSI 2.36
    rCSI 3.27%
    PRS 96.96
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.33
    rCSI 2.99%
    PRS 95.71
  • pancreatic ductal cell CL0002079
    CSI 2.33
    rCSI 4.52%
    PRS 97.33
  • retinal pigment epithelial cell CL0002586
    CSI 2.3
    rCSI 4.56%
    PRS 95.49
  • podocyte CL0000653
    CSI 2.18
    rCSI 9.69%
    PRS 97.37
  • glioblast CL0000030
    CSI 2.02
    rCSI 3.22%
    PRS 93.7
  • parietal epithelial cell CL1000452
    CSI 1.94
    rCSI 5.18%
    PRS 95.48
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.93
    rCSI 5%
    PRS 96.41
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.87
    rCSI 2.9%
    PRS 97.25
  • kidney collecting duct principal cell CL1001431
    CSI 1.78
    rCSI 8.94%
    PRS 94.86
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.66
    rCSI 2.01%
    PRS 83.76
  • forebrain radial glial cell CL0013000
    CSI 1.51
    rCSI 4.83%
    PRS 97.18
  • retinal ganglion cell CL0000740
    CSI 1.09
    rCSI 2.41%
    PRS 92.29
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.06
    rCSI 9.2%
    PRS 94.09
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.87
    rCSI 5.01%
    PRS 95.71
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.56
    rCSI 5.9%
    PRS 95.01

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 [VEPH1](/details-gene/79674), or Ventricular Zone Expressed PH Domain Containing 1, is a protein-coding gene located on chromosome 3. It encodes a plasma membrane-associated protein characterized by a pleckstrin homology (PH) domain, which is known to bind phosphatidylinositols. Functionally, [VEPH1](/details-gene/79674) is an important negative regulator of the Transforming Growth Factor-beta (TGF-beta) signaling pathway, acting by impeding the release of SMAD2 from the TGF-beta receptor complex [Link](https://doi.org/10.1073/pnas.1504671112). **Overall**, expression data reveals its significance in a diverse array of specialized cell types, with particularly high relevance in specific neuronal populations, such as [sncg GABAergic cortical interneurons](/details-cell/CL4023015), as well as various epithelial cells, [melanocytes](/details-cell/CL0000148), and [adipocytes](/details-cell/CL0000136), suggesting a broad but context-specific regulatory role across multiple tissues. ## Cellular Roles and Expression Landscape The expression profile of [VEPH1](/details-gene/79674) indicates a significant role in a variety of differentiated cell types across different lineages, rather than being restricted to a single tissue. **Overall**, its highest cellular significance index (CSI) is observed in [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 7.24), which is consistent with its initial characterization in the developing central nervous system [Link](https://doi.org/10.1016/j.biochi.2004.07.010). This suggests a specialized function in neuronal development or signaling within this specific interneuron subtype. Beyond the nervous system, [VEPH1](/details-gene/79674) demonstrates high significance in several other key cell populations: * **Pigment and Fat Cells:** It is a strong marker for [melanocytes](/details-cell/CL0000148) (CSI: 5.09) and [adipocytes](/details-cell/CL0000136) (CSI: 3.29), pointing towards a potential role in the biology of these cell types. * **Epithelial Tissues:** [VEPH1](/details-gene/79674) is prominently expressed across multiple epithelial lineages, particularly in the lung and kidney. This includes high significance in [epithelial cells of the lung](/details-cell/CL0000082) (CSI: 4.81), [lung ciliated cells](/details-cell/CL1000271) (CSI: 3.50), [epithelial cells of the proximal tubule](/details-cell/CL0002306) (CSI: 4.11), and [kidney connecting tubule epithelial cells](/details-cell/CL1000768) (CSI: 3.80). This widespread expression in secretory and transporting epithelia suggests a role in maintaining tissue homeostasis in these organs. * **Endothelial and Other Specialized Cells:** The gene also shows relevance in [blood vessel endothelial cells](/details-cell/CL0000071) (CSI: 3.19) and [intrahepatic cholangiocytes](/details-cell/CL0002538) (CSI: 3.14), highlighting its broad involvement in diverse physiological systems. The collective expression pattern suggests that [VEPH1](/details-gene/79674) is not a general housekeeping gene but rather a functionally important component in a wide range of specialized, terminally differentiated cells. ## Pathways and Molecular Function Functional annotation data aligns with the established role of [VEPH1](/details-gene/79674) as a signaling modulator, primarily through its interaction with phospholipids and key signaling pathways. * **Molecular Function:** Its core molecular functions include [phosphatidylinositol-5-phosphate binding](/details-ontology/GO:0010314), mediated by its PH domain, and general [protein binding](/details-ontology/GO:0005515). This binding capability is central to its localization and mechanism of action. The protein is primarily localized to the [plasma membrane](/details-ontology/GO:0005886). * **Biological Process:** [VEPH1](/details-gene/79674) is a known inhibitor of the TGF-beta signaling pathway. This is specified by its involvement in the [negative regulation of transforming growth factor beta receptor signaling pathway](/details-ontology/GO:0030512) and the downstream [negative regulation of smad protein signal transduction](/details-ontology/GO:0060392). Research has shown that the human ortholog of *Drosophila Melted* (VEPH1) directly impedes the release of SMAD2 from the TGF-beta type I receptor, thereby attenuating the signal [Link](https://doi.org/10.1073/pnas.1504671112). This function is consistent with its high expression in cell types where TGF-beta signaling plays a critical role in differentiation, proliferation, and pathology, such as epithelial cells and melanocytes. ## Research Directions The role of [VEPH1](/details-gene/79674) as a negative regulator of TGF-beta signaling, a pathway implicated in fibrosis, cancer, and development, combined with its specific cellular expression pattern, suggests several avenues for future research. ### Testable Hypotheses 1. **Role in Fibrosis Prevention:** Given its high expression in epithelial cells of the lung and kidney, and its function in inhibiting the pro-fibrotic TGF-beta pathway, it is hypothesized that [VEPH1](/details-gene/79674) acts as an endogenous protective factor against organ fibrosis. Reduced expression or function of [VEPH1](/details-gene/79674) in these cells may be a contributing factor to the pathogenesis of diseases like idiopathic pulmonary fibrosis or chronic kidney disease. 2. **Modulation of Melanoma Progression:** The TGF-beta pathway has a dual role in melanoma, initially acting as a tumor suppressor but later promoting invasion. Given the high significance of [VEPH1](/details-gene/79674) in [melanocytes](/details-cell/CL0000148), it is hypothesized that downregulation of [VEPH1](/details-gene/79674) is a key event in the switch of TGF-beta signaling from tumor-suppressive to pro-metastatic in melanoma, making it a potential biomarker for disease progression. 3. **Regulation of Neuronal Homeostasis:** The prominent expression of [VEPH1](/details-gene/79674) in [sncg GABAergic cortical interneurons](/details-cell/CL4023015) suggests it plays a critical role in modulating TGF-beta-dependent processes such as synaptic plasticity, neuronal survival, or circuit formation specifically within this inhibitory neuron population. ### Proposed Key Experiment To test the hypothesis that [VEPH1](/details-gene/79674) protects against renal fibrosis (Hypothesis 1), a kidney-specific conditional knockout mouse model (e.g., using a *Ksp1.3-Cre* driver) could be employed. These mice and their wild-type littermates would be subjected to a unilateral ureteral obstruction (UUO) surgical model to induce fibrosis. After 7-14 days, kidney tissues would be harvested and analyzed. The experimental readouts would include histological assessment of collagen deposition (e.g., Picrosirius Red staining) and immunohistochemistry for fibrotic markers like alpha-smooth muscle actin (α-SMA). Additionally, quantitative RT-PCR and Western blotting would be used to measure the expression of key fibrosis-related genes (e.g., *Col1a1*, *Fn1*, *Acta2*). A significantly exacerbated fibrotic phenotype in the knockout mice compared to controls would provide strong evidence for the protective role of [VEPH1](/details-gene/79674) in the kidney. ### Therapeutic Potential As an inhibitor of the often-pathogenic TGF-beta pathway, [VEPH1](/details-gene/79674) presents an interesting therapeutic target. The therapeutic strategy would likely involve **activation or potentiation** of its function rather than inhibition. For conditions driven by excessive TGF-beta signaling, such as organ fibrosis or certain cancers, developing small molecules that stabilize the [VEPH1](/details-gene/79674)-TGF-beta receptor interaction could be a viable approach. Alternatively, gene therapy strategies aimed at overexpressing [VEPH1](/details-gene/79674) specifically in affected tissues like the fibrotic lung or kidney could offer a novel way to restore cellular homeostasis and halt disease progression.

Genular Protein ID: 3090809342

Symbol: MELT_HUMAN

Name: Ventricular zone-expressed PH domain-containing protein homolog 1

UniProtKB Accession Codes:

Q14D04 D3DNL0 F5GZ91 Q2TAA9 Q3MIX2 Q6PEL3 Q86TL5 Q8TCR3 Q96SP7 Q9C0H1 Q9H9Q7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 6 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 6 SIGNOR 1 SMART 1 STRING 1 SUPFAM 2 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

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: 15388229

Title: Identification and characterization of Veph, a novel gene encoding a PH domain-containing protein expressed in the developing central nervous system of vertebrates.

PubMed ID: 15388229

DOI: 10.1016/j.biochi.2004.07.010

PubMed ID: 16054033

Title: Drosophila Melted modulates FOXO and TOR activity.

PubMed ID: 16054033

DOI: 10.1016/j.devcel.2005.07.004

PubMed ID: 26039994

Title: Human ortholog of Drosophila Melted impedes SMAD2 release from TGF-beta receptor I to inhibit TGF-beta signaling.

PubMed ID: 26039994

DOI: 10.1073/pnas.1504671112

Sequence Information:

  • Length: 833
  • Mass: 94745
  • Checksum: 34995B4AB43474A4
  • Sequence:
    • MHQLFRLVLG QKDLSRAGDL FSLDDSEIED SLTEALEQIK IISSSSDYQT NNNDQAVVEI 
CITRITTAIR ETESIEKHAK ALVGLWDSCL EHNLRPFGKD EDTPHAKIAS DIMSCILQNY 
NRPPVMALAI PIAVKFLHRG NKELCRNMSN YLSLAAITKA DLLADHTEVI VKSILQGNTM 
LLRVLPAVYE KQPQPINRHL TELLALMSQL EQPEQYHLLR LLHVAAKKKQ LEVVQKCIPF 
LIGHLKDSTH NDIILNILIE IAVYEPVALN SFLPMLKEIG ERFPYLTGQM ARIYGAVGHV 
DEERARSCLT YLVSQLANME HSFHHILLLE IKSITDTFSS ILGPQSRDIF RMSNSFTAIA 
KLLTRQLENT KAGSGRRKIS TEIEFPEKLE ETKLIVTENE DHEKLQVKIQ AFEDKINAGS 
NTPGSIRRYS LGQVSKEERK NIRFNRSKSL AFHTMLTKGV GSDDGEDENR GDIPASISLS 
EIDPLGQGND KLPFKTDTER SQLGESSVSY PNIIHIDSEN LSETVKENSQ EETPETTASP 
IEYQDKLYLH LKKNLSKVKA YAMEIGKKIP VPDQCTIEDT VRSCVAKLFF TCSLKGHYCL 
YSKSSFILIS QEPQPWIQIM FLFQQSLFPE PLSIQSHSVQ FLRALWEKTQ AGGAHSFETA 
MMESTFPQQK DLDQVQLHLE EVRFFDVFGF SETAGAWQCF MCNNPEKATV VNQDGQPLIE 
GKLKEKQVRW KFIKRWKTRY FTLAGNQLLF QKGKSKDDPD DCPIELSKVQ SVKAVAKKRR 
DRSLPRAFEI FTDNKTYVFK AKDEKNAEEW LQCINVAVAQ AKERESREVT TYL