Details for: HEPN1

Gene ID: 641654

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: HEPN1

Ensembl ID: ENSG00000221932

Description: hepatocellular carcinoma, down-regulated 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Significant Cells

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

  • Bergmann glial cell CL0000644
    CSI 15.85
    rCSI 21.69%
    PRS 95.8
  • forebrain radial glial cell CL0013000
    CSI 12.3
    rCSI 39.48%
    PRS 98.42
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 6.91
    rCSI 12.56%
    PRS 95.98
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.21
    rCSI 9.44%
    PRS 95.25
  • neural progenitor cell CL0011020
    CSI 3
    rCSI 13.2%
    PRS 93.53
  • glioblast CL0000030
    CSI 2.75
    rCSI 4.38%
    PRS 96.04
  • adipocyte CL0000136
    CSI 2.71
    rCSI 3.48%
    PRS 95.96
  • suprabasal keratinocyte CL4033013
    CSI 2.64
    rCSI 4.31%
    PRS 85.16

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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Legend:
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  • 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 [HEPN1](/details-gene/641654), or *hepatocellular carcinoma, down-regulated 1*, is a protein-coding gene located on chromosome 11q24.2. Despite its name, which originates from its observed downregulation in liver cancer, expression data suggests its primary role is within the central nervous system. It shows highly significant expression in various glial cell populations, including [Bergmann glial cells](/details-cell/CL0000644) and [forebrain radial glial cells](/details-cell/CL0013000). Functional studies indicate that [HEPN1](/details-gene/641654) has tumor-suppressive properties, capable of inhibiting cell growth and inducing apoptosis, at least in the context of liver cancer cell lines ([Link](https://doi.org/10.1016/s0168-8278(03)00359-3)). ## Cellular Roles and Expression Landscape The expression profile of [HEPN1](/details-gene/641654) points towards a specialized function in neurodevelopment and glial cell biology. **Overall**, the gene's significance is most pronounced in cells of the glial lineage. It is a top marker for [Bergmann glial cells](/details-cell/CL0000644) (CSI: 15.85) and [forebrain radial glial cells](/details-cell/CL0013000) (CSI: 12.30), which are crucial for neuronal guidance and development. High significance is also observed in progenitor and mature glial cell types, including [differentiation-committed oligodendrocyte precursors](/details-cell/CL4023059) (CSI: 6.91), [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 4.21), and [neural progenitor cells](/details-cell/CL0011020) (CSI: 3.00). Interestingly, [HEPN1](/details-gene/641654) is also significantly expressed in [glioblasts](/details-cell/CL0000030) (CSI: 2.75), the malignant cells of glioblastoma, suggesting its function may be relevant in the context of brain tumors. Beyond the nervous system, the gene shows moderate significance in diverse cell types such as [adipocytes](/details-cell/CL0000136) and [suprabasal keratinocytes](/details-cell/CL4033013), which may indicate broader, context-dependent roles in other tissues. The collective expression pattern suggests that while named for its role in liver cancer, the primary physiological function of [HEPN1](/details-gene/641654) is likely concentrated within the glial compartments of the central nervous system. ## Pathways and Molecular Function While detailed pathway annotations are limited, functional evidence strongly suggests [HEPN1](/details-gene/641654) is involved in the negative regulation of cell proliferation and the promotion of programmed cell death (apoptosis). A foundational study demonstrated that re-expression of [HEPN1](/details-gene/641654) in the HepG2 liver cancer cell line, where it is normally downregulated, resulted in suppressed cell growth and induced apoptosis ([Link](https://doi.org/10.1016/s0168-8278(03)00359-3)). This classifies it as a putative tumor suppressor. The precise molecular mechanism by which it exerts these effects remains to be elucidated. Its high expression in various glial progenitor cells suggests it may play a role in regulating cell cycle exit during differentiation or in maintaining homeostasis in mature glial populations. ## Research Directions The discrepancy between the high expression of [HEPN1](/details-gene/641654) in neural cells and its characterization as a liver-specific tumor suppressor presents several avenues for future investigation. **Testable Hypotheses:** 1. Given its prominent expression in glial progenitor populations ([forebrain radial glial cell](/details-cell/CL0013000), [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059)), [HEPN1](/details-gene/641654) may function as a key regulator of glial cell differentiation. Its loss could impair the maturation of astrocytes or oligodendrocytes, potentially contributing to neurodevelopmental or demyelinating disorders. 2. The established anti-proliferative function of [HEPN1](/details-gene/641654) ([Link](https://doi.org/10.1016/s0168-8278(03)00359-3)) and its expression in [glioblasts](/details-cell/CL0000030) suggest it may act as an endogenous tumor suppressor in the brain. Downregulation or silencing of [HEPN1](/details-gene/641654) could be a critical event in the initiation or progression of glioblastoma. **Proposed Experiment:** To test the hypothesis that [HEPN1](/details-gene/641654) is a tumor suppressor in the brain, a CRISPR-Cas9-mediated knockout could be performed in human-derived glioma stem cell (GSC) lines that endogenously express the gene. The resulting [HEPN1](/details-gene/641654)-null GSCs would be compared to isogenic controls. Key assays would include in vitro sphere-formation assays to assess self-renewal and proliferation, and in vivo orthotopic xenograft models in immunocompromised mice to evaluate tumor growth, invasion, and overall survival. RNA-sequencing of the knockout and control cells could further identify the downstream pathways regulated by [HEPN1](/details-gene/641654). **Therapeutic Potential:** As a putative tumor suppressor, the therapeutic strategy for [HEPN1](/details-gene/641654) would involve its **activation** or functional restoration in cancer cells. This is challenging but could potentially be achieved through gene therapy approaches (e.g., using AAV vectors to re-introduce the gene into tumor cells) or by developing small molecules that mimic its downstream effects, such as activating the apoptotic pathways it regulates. Given its high expression in multiple healthy glial cell types, systemic therapies would need to be carefully designed to avoid off-target effects in the healthy brain, making targeted delivery systems a critical component of any potential therapeutic development.

Genular Protein ID: 3886689175

Symbol: HEPN1_HUMAN

Name: Putative cancer susceptibility gene HEPN1 protein

UniProtKB Accession Codes:

Q6WQI6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PathwayCommons 1 PaxDb 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 12971969

Title: HEPN1, a novel gene that is frequently down-regulated in hepatocellular carcinoma, suppresses cell growth and induces apoptosis in HepG2 cells.

PubMed ID: 12971969

DOI: 10.1016/s0168-8278(03)00359-3

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

Sequence Information:

  • Length: 88
  • Mass: 10305
  • Checksum: 86B4FBE3F21C6EE0
  • Sequence:
    • MGNWGLGIAP WVDGESELEF RRLGMQGPLE ALRRREWNTQ RASFSFSFLI ALSPHTVDYC 
HSYELFNRRW HGHVLATQRP SLFILMLV