Details for: ENTREP2

Gene ID: 23359

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: ENTREP2

Ensembl ID: ENSG00000104059

Description: endosomal transmembrane epsin interactor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 26.81
    rCSI 33.36%
    PRS 95.62
  • VIP GABAergic cortical interneuron CL4023016
    CSI 25.39
    rCSI 30.32%
    PRS 96.06
  • sst GABAergic cortical interneuron CL4023017
    CSI 24.8
    rCSI 31.97%
    PRS 96.62
  • sncg GABAergic cortical interneuron CL4023015
    CSI 22.1
    rCSI 35.54%
    PRS 96
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 15.58
    rCSI 26.15%
    PRS 96.46
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 14.63
    rCSI 35.56%
    PRS 95.02
  • L6b glutamatergic cortical neuron CL4023038
    CSI 14.22
    rCSI 44.45%
    PRS 96.22
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 12.65
    rCSI 22.34%
    PRS 96.22
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 12.41
    rCSI 44.66%
    PRS 95.43
  • choroid plexus epithelial cell CL0000706
    CSI 12.1
    rCSI 19.81%
    PRS 97.44
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 11.17
    rCSI 42.21%
    PRS 95.64
  • parietal epithelial cell CL1000452
    CSI 10.63
    rCSI 28.41%
    PRS 97.92
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 10.31
    rCSI 32.24%
    PRS 96.6
  • vascular leptomeningeal cell CL4023051
    CSI 9.9
    rCSI 17.36%
    PRS 97.64
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 9.62
    rCSI 23%
    PRS 94.98
  • mesothelial cell CL0000077
    CSI 9.4
    rCSI 36.74%
    PRS 95.03
  • interneuron CL0000099
    CSI 9.04
    rCSI 18.14%
    PRS 97.55
  • inhibitory interneuron CL0000498
    CSI 8.69
    rCSI 20.07%
    PRS 96.29
  • epithelial cell of proximal tubule CL0002306
    CSI 8.02
    rCSI 19.59%
    PRS 96.71
  • neuron CL0000540
    CSI 7.61
    rCSI 20.27%
    PRS 93.87
  • retinal ganglion cell CL0000740
    CSI 7.51
    rCSI 16.6%
    PRS 96.13
  • cerebellar granule cell CL0001031
    CSI 6.2
    rCSI 9.11%
    PRS 96.99
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 6.04
    rCSI 8.57%
    PRS 98.4
  • amacrine cell CL0000561
    CSI 5.76
    rCSI 16.69%
    PRS 96.29
  • pancreatic ductal cell CL0002079
    CSI 5.73
    rCSI 11.14%
    PRS 98.73
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.67
    rCSI 14.39%
    PRS 98
  • GABAergic amacrine cell CL4030027
    CSI 5.31
    rCSI 18.2%
    PRS 94
  • glycinergic amacrine cell CL4030028
    CSI 5.22
    rCSI 13.61%
    PRS 95.9
  • neural crest cell CL0011012
    CSI 5.21
    rCSI 4.12%
    PRS 98.25
  • small intestine goblet cell CL1000495
    CSI 5.17
    rCSI 11.32%
    PRS 99.03
  • central nervous system neuron CL2000029
    CSI 4.7
    rCSI 34.58%
    PRS 96.59
  • dopaminergic neuron CL0000700
    CSI 4.46
    rCSI 25.19%
    PRS 95.25
  • renal beta-intercalated cell CL0002201
    CSI 4.21
    rCSI 10.03%
    PRS 98.75
  • cerebral cortex endothelial cell CL1001602
    CSI 4.1
    rCSI 7.08%
    PRS 97.51
  • glutamatergic neuron CL0000679
    CSI 4.05
    rCSI 8.32%
    PRS 94.12
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 4.01
    rCSI 23.62%
    PRS 95.76
  • endocardial cell CL0002350
    CSI 3.99
    rCSI 19.12%
    PRS 98.02
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.88
    rCSI 8.7%
    PRS 96.25
  • BEST4+ enteroycte CL4030026
    CSI 3.78
    rCSI 4.7%
    PRS 98.47
  • serotonergic neuron CL0000850
    CSI 3.58
    rCSI 16.01%
    PRS 92.8
  • GABAergic neuron CL0000617
    CSI 3.46
    rCSI 11.6%
    PRS 93.89
  • pulmonary alveolar type 1 cell CL0002062
    CSI 3.46
    rCSI 19.95%
    PRS 97.93
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 3.4
    rCSI 7.38%
    PRS 94.01
  • H2 horizontal cell CL0004218
    CSI 3.17
    rCSI 15.78%
    PRS 96.39
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 3.1
    rCSI 10.19%
    PRS 94.52
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 2.93
    rCSI 31.03%
    PRS 97.55
  • renal principal cell CL0005009
    CSI 2.7
    rCSI 7.02%
    PRS 98.81
  • regular atrial cardiac myocyte CL0002129
    CSI 2.7
    rCSI 8.7%
    PRS 97.41
  • endothelial cell of vascular tree CL0002139
    CSI 2.64
    rCSI 14.42%
    PRS 97.22
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.63
    rCSI 4.78%
    PRS 96.71
  • macroglial cell CL0000126
    CSI 2.62
    rCSI 6.73%
    PRS 97.17
  • direct pathway medium spiny neuron CL4023026
    CSI 2.01
    rCSI 48.11%
    PRS 94.51
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.01
    rCSI 48.41%
    PRS 94.23
  • OFF midget ganglion cell CL4033047
    CSI 1.93
    rCSI 39.21%
    PRS 95.68
  • ON midget ganglion cell CL4033046
    CSI 1.42
    rCSI 28.99%
    PRS 95.67
  • ON parasol ganglion cell CL4033052
    CSI 1.02
    rCSI 14.54%
    PRS 95.6

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 [ENTREP2](/details-gene/23359) (endosomal transmembrane epsin interactor 2) is a protein-coding gene located on chromosome 15q13.1. It encodes a transmembrane protein whose function is not well-characterized but is suggested by its name to be involved in endosomal processes. Expression data indicates that [ENTREP2](/details-gene/23359) is a significant marker predominantly within the central nervous system. **Overall**, it shows exceptionally high and specific expression in various subtypes of cortical neurons, particularly GABAergic interneurons, suggesting a fundamental role in neuronal function, identity, or maintenance. ## Cellular Roles and Expression Landscape The expression profile of [ENTREP2](/details-gene/23359) strongly points to a specialized role within the mammalian brain. The gene demonstrates the highest significance in multiple, distinct classes of inhibitory neurons. **Overall**, it is a top marker for [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 26.81), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 25.39), and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 24.80), underscoring its potential importance across diverse interneuron populations responsible for regulating cortical circuits. Beyond these specific subtypes, [ENTREP2](/details-gene/23359) is also highly significant in various excitatory glutamatergic neurons, including [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) and [L6b glutamatergic cortical neuron](/details-cell/CL4023038). This broad yet specific expression pattern across both inhibitory and excitatory neuronal lineages suggests that [ENTREP2](/details-gene/23359) may be involved in a cellular process fundamental to a wide range of cortical neurons rather than a function restricted to a single cell type. Notably, significant expression is also observed in non-neuronal cell types within or associated with the CNS, such as [choroid plexus epithelial cell](/details-cell/CL0000706) and [vascular leptomeningeal cell](/details-cell/CL4023051). This pattern may indicate a role in brain homeostasis or the blood-brain barrier. The gene's identification has been supported by several large-scale cDNA and gene prediction projects [Link](https://doi.org/10.1101/gr.2596504), [Link](https://doi.org/10.1093/dnares/5.1.31). ## Pathways and Molecular Function Functional annotation for [ENTREP2](/details-gene/23359) is currently sparse, but available data aligns with its presumed protein characteristics. The gene is associated with the Gene Ontology cellular component term **[Membrane (GO:0016020)](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)**. This is consistent with its predicted nature as a transmembrane protein and its designation as "endosomal transmembrane epsin interactor 2," which implies localization to endosomal membranes. Epsin is a key protein in clathrin-mediated endocytosis, suggesting that [ENTREP2](/details-gene/23359) may function as a cargo receptor or an accessory protein in the endocytic pathway, a process vital for synaptic vesicle recycling and receptor turnover in the highly active neuronal cells where it is predominantly expressed. ## Research Directions The specific and high-level expression of [ENTREP2](/details-gene/23359) in cortical neurons, coupled with its putative role in endosomal trafficking, presents several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in diverse GABAergic interneurons, [ENTREP2](/details-gene/23359) may be a critical regulator of inhibitory synapse function. It could mediate the endosomal sorting and recycling of GABA receptors or associated proteins, thereby modulating the strength and plasticity of inhibitory neurotransmission. 2. The gene's consistent high expression across functionally distinct neuronal populations (e.g., inhibitory pvalb-positive and excitatory L2/3-6 IT neurons) suggests it may be involved in a fundamental 'housekeeping' role essential for neuronal health, such as maintaining membrane integrity or regulating the trafficking of essential proteins common to most neurons. **Experimental Approach:** To test the hypothesis that [ENTREP2](/details-gene/23359) regulates inhibitory synapse function (Hypothesis 1), a targeted experiment could be designed. CRISPR-Cas9-mediated knockdown or knockout of [ENTREP2](/details-gene/23359) in human iPSC-derived cortical interneurons would be a key first step. The functional consequences could be assessed by measuring changes in the surface expression levels of GABAA receptor subunits using immunocytochemistry and quantitative imaging. Furthermore, patch-clamp electrophysiology could be employed to determine if the loss of [ENTREP2](/details-gene/23359) alters the frequency or amplitude of miniature inhibitory postsynaptic currents (mIPSCs), providing a direct functional readout of its role at the synapse. **Therapeutic Potential:** The high specificity of [ENTREP2](/details-gene/23359) expression within the central nervous system makes it an intriguing, albeit challenging, therapeutic target. Dysregulation of cortical interneuron function is implicated in neurological and psychiatric disorders such as epilepsy and schizophrenia. If [ENTREP2](/details-gene/23359) is found to be a key modulator of neuronal excitability, it could represent a target for novel therapeutics. However, as a transmembrane protein likely involved in a core cellular process, targeting it would require high specificity to avoid off-target effects. Its CNS-specific expression is advantageous, but the blood-brain barrier poses a significant hurdle for drug delivery. Whether inhibition or activation would be therapeutically beneficial remains to be determined and depends entirely on its precise molecular function.

Genular Protein ID: 821218482

Symbol: EREP2_HUMAN

Name: Transmembrane protein 228

UniProtKB Accession Codes:

O60320 A0PK09

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 STRING 1 TCDB 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 16344560

Title: Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

PubMed ID: 16344560

DOI: 10.1101/gr.4039406

PubMed ID: 9628581

Title: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9628581

DOI: 10.1093/dnares/5.1.31

Sequence Information:

  • Length: 539
  • Mass: 56544
  • Checksum: 43B9F5A654985E91
  • Sequence:
    • MPPAGGPRAP RPAALPRSLS RLRECPGRSR IVLALGATQM ALGCLIVAVS FAALALTTSA 
RVRHSCPFWA GFSVLLSGLI GVVSWKRPLS LVITFFMLLS AVCVMLNLAG SILSCQNAQL 
VNSLEGCQLI KFDSVEVCVC CELQHQSSGC SNLGETLKLN PLQENCNAVR LTLKDLLFSV 
CALNVLSTIV CALATAMCCM QMVSSDVLQM FLPQRSHPAN PTCVTPHGTV LHQTLDFDEF 
IPPLPPPPYY PPEYTCTPST EAQRGLHLDF APSPFGTLYD VAINSPGLLY PAELPPPYEA 
VVGQPPASQV TSIGQQVAES SSGDPNTSAG FSTPVPADST SLLVSEGTAT PGSSPSPDGP 
VGAPAPSEPA LPPGHVSPED PGMGSQVQPG PGRVSRSTSD PTLCTSSMAG DASSHRPSCS 
QDLEAGLSEA VPGSASMSRS ATAACRAQLS PAGDPDTWKT DQRPTPEPFP ATSKERPRSL 
VDSKAYADAR VLVAKFLEHS HCALPTEAQH MVGAMRLAVT NEERLEEEAV FGADVLDQV