Details for: ENHO

Gene ID: 375704

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: ENHO

Ensembl ID: ENSG00000168913

Description: energy homeostasis associated

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 15.84
    rCSI 33.68%
    PRS 79.83
  • forebrain radial glial cell CL0013000
    CSI 12.43
    rCSI 39.87%
    PRS 86.15
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 5.83
    rCSI 7.48%
    PRS 82.08
  • skin fibroblast CL0002620
    CSI 3.8
    rCSI 3.28%
    PRS 85.37
  • dendritic cell, human CL0001056
    CSI 3.57
    rCSI 5.48%
    PRS 92.37
  • Bergmann glial cell CL0000644
    CSI 3.38
    rCSI 4.63%
    PRS 77.4
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.28
    rCSI 3.16%
    PRS 84.82
  • conventional dendritic cell CL0000990
    CSI 2.87
    rCSI 2.4%
    PRS 82.81
  • neural crest cell CL0011012
    CSI 2.79
    rCSI 2.21%
    PRS 76.57
  • interneuron CL0000099
    CSI 2.72
    rCSI 5.45%
    PRS 77.86
  • mature astrocyte CL0002627
    CSI 2.62
    rCSI 11.14%
    PRS 78.98
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.55
    rCSI 3.08%
    PRS 91.92
  • radial glial cell CL0000681
    CSI 2.52
    rCSI 3.51%
    PRS 84.05
  • dendritic cell CL0000451
    CSI 2.27
    rCSI 2.8%
    PRS 86.91
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.23
    rCSI 6.58%
    PRS 86.41
  • glioblast CL0000030
    CSI 2.2
    rCSI 3.51%
    PRS 77.72
  • peripheral nervous system neuron CL2000032
    CSI 1.96
    rCSI 2.67%
    PRS 78.35
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.84
    rCSI 4.13%
    PRS 70.78
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.73
    rCSI 2.07%
    PRS 70
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.7
    rCSI 2.74%
    PRS 71.25
  • stromal cell CL0000499
    CSI 1.66
    rCSI 4.68%
    PRS 81.07
  • neural progenitor cell CL0011020
    CSI 1.49
    rCSI 6.55%
    PRS 74.41
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.36
    rCSI 2.41%
    PRS 69.43
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.3
    rCSI 1.68%
    PRS 71.02
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1
    rCSI 1.67%
    PRS 69.85
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.73
    rCSI 2.27%
    PRS 73.53
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.72
    rCSI 2.25%
    PRS 71.36
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.65
    rCSI 2.34%
    PRS 67.84
  • Cajal-Retzius cell CL0000695
    CSI 0.44
    rCSI 3.45%
    PRS 88.71
  • pre-conventional dendritic cell CL0002010
    CSI 0.2
    rCSI 2.63%
    PRS 96.1

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 [ENHO](/details-gene/375704) (Energy Homeostasis Associated) is a protein-coding gene located on chromosome 9p13.3. It encodes Adropin, a secreted peptide hormone primarily involved in regulating energy and metabolic homeostasis [Link](https://doi.org/10.1016/j.cmet.2008.10.011). Functionally, [ENHO](/details-gene/375704) participates in signal transduction and has been implicated in the positive regulation of the Notch signaling pathway. **Overall**, expression data reveals that [ENHO](/details-gene/375704) is a highly significant marker for various neural progenitor and glial cell populations, including [progenitor cells](/details-cell/CL0011026) and [forebrain radial glial cells](/details-cell/CL0013000), suggesting a key role in central nervous system development and maintenance. ## Cellular Roles and Expression Landscape The expression profile of [ENHO](/details-gene/375704) points to a specialized function within the central nervous system, particularly during development and in glial cell lineages. The gene exhibits its highest significance in [progenitor cells](/details-cell/CL0011026) (CSI: 15.84) and [forebrain radial glial cells](/details-cell/CL0013000) (CSI: 12.43), underscoring its potential importance in neurogenesis and brain architecture. This neural-centric role is further supported by its notable expression in related cell types such as [neuroblasts (sensu Vertebrata)](/details-cell/CL0000031), [Bergmann glial cells](/details-cell/CL0000644), [mature astrocytes](/details-cell/CL0002627), and [interneurons](/details-cell/CL0000099). The consistent high significance across these populations suggests [ENHO](/details-gene/375704) may be involved in cell fate determination, migration, or metabolic support within the brain. Additionally, [ENHO](/details-gene/375704) shows moderate but significant expression in several subtypes of [dendritic cells](/details-cell/CL0000451), including [conventional dendritic cells](/details-cell/CL0000990) and [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399), which may indicate a secondary role in immune modulation or tissue surveillance. ## Pathways and Molecular Function [ENHO](/details-gene/375704) encodes a secreted protein, Adropin, which functions as a hormone ([GO:0005179](https://www.ebi.ac.uk/QuickGO/term/GO:0005179)) and is found in the [extracellular region](/details-cell/GO:0005576). Its primary biological activities are linked to signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO:0007165)) and energy metabolism regulation. Notably, [ENHO](/details-gene/375704) is annotated as a positive regulator of the Notch signaling pathway ([GO:0045747](https://www.ebi.ac.uk/QuickGO/term/GO:0045747)). This function is highly consistent with its prominent expression in neural progenitor and glial cell populations, as Notch signaling is a cornerstone of cell fate decisions during neurodevelopment, controlling the balance between proliferation and differentiation. The secretion of its protein product, Adropin, suggests it may act in a paracrine manner to modulate Notch activity in neighboring cells within the neurogenic niche. ## Research Directions The unique expression pattern and functional annotations of [ENHO](/details-gene/375704) suggest it operates at the intersection of neurodevelopment and systemic metabolism. This dual role opens several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high expression in [progenitor cells](/details-cell/CL0011026) and its link to Notch signaling, [ENHO](/details-gene/375704)-derived Adropin acts as a key paracrine factor within the developing brain, regulating the differentiation and maintenance of neural stem cell pools. 2. Astrocytic expression of [ENHO](/details-gene/375704) in the mature brain may function as a local sensor of neuronal activity and metabolic state, releasing Adropin to modulate synaptic function and provide neuroprotective metabolic support. **Experimental Approach:** To test the first hypothesis regarding [ENHO](/details-gene/375704)'s role in neurodevelopment, one could utilize an *in vitro* organoid model derived from human induced pluripotent stem cells (iPSCs). CRISPR-Cas9 could be used to generate an [ENHO](/details-gene/375704) knockout iPSC line. Upon differentiation into cerebral organoids, the knockout and wild-type lines could be compared using single-cell RNA sequencing (scRNA-seq). This would allow for a detailed assessment of changes in cell-type proportions (e.g., a shift in the ratio of neural progenitors to mature neurons) and a direct analysis of transcriptional changes in Notch pathway target genes (e.g., *HES1*, *HEY1*) within specific cell populations. **Therapeutic Potential:** As the gene product, Adropin, is a secreted hormone with a known role in maintaining metabolic health, [ENHO](/details-gene/375704) presents a compelling therapeutic target. The strategy would focus on **activation or supplementation** rather than inhibition. Recombinant Adropin or small-molecule agonists that enhance [ENHO](/details-gene/375704) expression or Adropin receptor signaling could hold promise for treating metabolic disorders, such as type 2 diabetes and non-alcoholic fatty liver disease. Furthermore, its strong CNS expression suggests potential utility in neuro-metabolic or neurodegenerative conditions where brain energy homeostasis is compromised.

Genular Protein ID: 2798820289

Symbol: ENHO_HUMAN

Name: Adropin

UniProtKB Accession Codes:

Q6UWT2 Q8N666

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 2 Ensembl 1 GO 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 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: 19041763

Title: Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.

PubMed ID: 19041763

DOI: 10.1016/j.cmet.2008.10.011

Sequence Information:

  • Length: 76
  • Mass: 7927
  • Checksum: 815301219DFE3921
  • Sequence:
    • MGAAISQGAL IAIVCNGLVG FLLLLLWVIL CWACHSRSAD VDSLSESSPN SSPGPCPEKA 
PPPQKPSHEG SYLLQP