Details for: ZPR1

Gene ID: 8882

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: ZPR1

Ensembl ID: ENSG00000109917

Description: ZPR1 zinc finger

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mature B cell CL0000785
    CSI 5.93
    rCSI 5.15%
    PRS 92.04
  • dendritic cell, human CL0001056
    CSI 5.81
    rCSI 8.92%
    PRS 91.27
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.91
    rCSI 3.93%
    PRS 93.79
  • club cell CL0000158
    CSI 4.33
    rCSI 6.34%
    PRS 79.25
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.29
    rCSI 3.27%
    PRS 94.7
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 3.87
    rCSI 3.8%
    PRS 94.76
  • unswitched memory B cell CL0000970
    CSI 3.77
    rCSI 3.17%
    PRS 94.53
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.77
    rCSI 3.63%
    PRS 83.59
  • plasmablast CL0000980
    CSI 3.62
    rCSI 2.85%
    PRS 88.37
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 3.28
    rCSI 9.42%
    PRS 96.72
  • mesenchymal cell CL0008019
    CSI 3.24
    rCSI 8.22%
    PRS 77.97
  • double negative thymocyte CL0002489
    CSI 3.22
    rCSI 2.24%
    PRS 93.82
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.94
    rCSI 2.11%
    PRS 94.58
  • interneuron CL0000099
    CSI 2.92
    rCSI 5.87%
    PRS 75.8
  • pro-B cell CL0000826
    CSI 2.89
    rCSI 2.39%
    PRS 86.49
  • neural crest cell CL0011012
    CSI 2.85
    rCSI 2.25%
    PRS 74.67
  • progenitor cell CL0011026
    CSI 2.77
    rCSI 5.89%
    PRS 78.19
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.76
    rCSI 1.86%
    PRS 94.72
  • CD4-positive helper T cell CL0000492
    CSI 2.73
    rCSI 2.06%
    PRS 94.22
  • immature B cell CL0000816
    CSI 2.72
    rCSI 2.02%
    PRS 92.71
  • early lymphoid progenitor CL0000936
    CSI 2.62
    rCSI 2.3%
    PRS 88.64
  • perivascular cell CL4033054
    CSI 2.62
    rCSI 3.58%
    PRS 88.37
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 2.6
    rCSI 4.06%
    PRS 95.57
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.59
    rCSI 2%
    PRS 87.47
  • epithelial cell of lung CL0000082
    CSI 2.57
    rCSI 2.13%
    PRS 85.28
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.52
    rCSI 2.91%
    PRS 76.73
  • intermediate monocyte CL0002393
    CSI 2.47
    rCSI 3.72%
    PRS 89.13
  • activated type II NK T cell CL0000931
    CSI 2.46
    rCSI 2.77%
    PRS 94.34
  • colon epithelial cell CL0011108
    CSI 2.36
    rCSI 2.47%
    PRS 81.71
  • natural T-regulatory cell CL0000903
    CSI 2.32
    rCSI 4.39%
    PRS 97.28
  • keratinocyte CL0000312
    CSI 2.26
    rCSI 1.89%
    PRS 86.19
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.19
    rCSI 6.46%
    PRS 84.93
  • granulocyte CL0000094
    CSI 2.1
    rCSI 3.2%
    PRS 90.12
  • pulmonary ionocyte CL0017000
    CSI 2.08
    rCSI 2.53%
    PRS 89.74
  • hematopoietic stem cell CL0000037
    CSI 2.06
    rCSI 1.37%
    PRS 86.51
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.02
    rCSI 1.82%
    PRS 82.83
  • stem cell CL0000034
    CSI 2.01
    rCSI 1.94%
    PRS 78.76
  • ciliated epithelial cell CL0000067
    CSI 1.97
    rCSI 1.74%
    PRS 74.29
  • group 3 innate lymphoid cell CL0001071
    CSI 1.91
    rCSI 1.44%
    PRS 89.27
  • lung macrophage CL1001603
    CSI 1.87
    rCSI 4.18%
    PRS 90.42
  • mature alpha-beta T cell CL0000791
    CSI 1.87
    rCSI 6.77%
    PRS 96.26
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.87
    rCSI 2.39%
    PRS 80.61
  • extravillous trophoblast CL0008036
    CSI 1.85
    rCSI 2.29%
    PRS 82.45
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.75
    rCSI 2.26%
    PRS 68.84
  • radial glial cell CL0000681
    CSI 1.75
    rCSI 2.43%
    PRS 82.76
  • multi-ciliated epithelial cell CL0005012
    CSI 1.66
    rCSI 1.66%
    PRS 78.45
  • T-helper 1 cell CL0000545
    CSI 1.54
    rCSI 2.79%
    PRS 95.45
  • erythrocyte CL0000232
    CSI 1.47
    rCSI 3.33%
    PRS 84.01
  • basal cell of prostate epithelium CL0002341
    CSI 1.42
    rCSI 4.12%
    PRS 89.03
  • basal cell CL0000646
    CSI 1.42
    rCSI 1.9%
    PRS 82.25
  • Langerhans cell CL0000453
    CSI 1.36
    rCSI 2.08%
    PRS 92.94
  • common dendritic progenitor CL0001029
    CSI 1.31
    rCSI 1.65%
    PRS 91.19
  • pancreatic ductal cell CL0002079
    CSI 1.3
    rCSI 2.53%
    PRS 87.04
  • placental villous trophoblast CL2000060
    CSI 1.28
    rCSI 1.98%
    PRS 83.14
  • promyelocyte CL0000836
    CSI 1.24
    rCSI 1.8%
    PRS 88.64
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.24
    rCSI 3.87%
    PRS 69.21
  • megakaryocyte CL0000556
    CSI 1.08
    rCSI 4.7%
    PRS 87.91
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.71
    rCSI 3.57%
    PRS 93.87
  • primitive red blood cell CL0002355
    CSI 0.62
    rCSI 3.32%
    PRS 88.74
  • epithelial cell of urethra CL1000296
    CSI 0.18
    rCSI 4.43%
    PRS 89.75

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 [ZPR1](/details-gene/8882) is a protein-coding gene that encodes ZPR1 zinc finger, a protein with crucial roles in fundamental cellular processes including cell cycle progression, RNA processing, and signal transduction. Its function is tightly linked to cellular proliferation, as evidenced by its high expression in a wide array of actively dividing immune cells, including [mature B cell](/details-cell/CL0000785)s, [dendritic cell, human](/details-cell/CL0001056)s, and thymocytes. Research has established its interaction with key cellular machinery, such as the epidermal growth factor receptor and the SMN protein, linking it to both growth signaling and the pathogenesis of Spinal Muscular Atrophy (SMA) [Link](https://doi.org/10.1126/science.272.5269.1797), [Link](https://doi.org/10.1038/35070059). Mutations in [ZPR1](/details-gene/8882) are also associated with a distinct developmental syndrome, highlighting its essential role in human growth and development [Link](https://doi.org/10.1111/cge.13388). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ZPR1](/details-gene/8882) underscores its importance in highly proliferative and transcriptionally active cell types. The gene shows its highest significance in the hematopoietic system, particularly within the adaptive immune lineage. It is a top marker for [mature B cell](/details-cell/CL0000785) (CSI: 5.93) and [dendritic cell, human](/details-cell/CL0001056) (CSI: 5.81), suggesting a critical function in antigen presentation and B cell maturation. High significance is also observed across T cell development and differentiation, including in [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810) (CSI: 4.91), [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 4.29), and [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792) (CSI: 3.87). This broad pattern across diverse lymphocyte populations points to a foundational role in immune cell biology. Beyond the immune system, [ZPR1](/details-gene/8882) is also significantly expressed in specific epithelial and developmental cell types. Its high significance in [club cell](/details-cell/CL0000158)s (CSI: 4.33) of the lung and [fallopian tube secretory epithelial cell](/details-cell/CL4030006)s (CSI: 3.77) may indicate a role in the maintenance and function of these secretory tissues. Furthermore, its expression in [mesenchymal cell](/details-cell/CL0008019)s (CSI: 3.24) and [interneuron](/details-cell/CL0000099)s (CSI: 2.92) is consistent with its documented involvement in developmental processes and neuronal function. ## Pathways and Molecular Function The functional annotations for [ZPR1](/details-gene/8882) align closely with its observed expression pattern in proliferating cells. It is implicated in the 'Positive regulation of cell cycle' ([GO:0045787](https://www.ebi.ac.uk/QuickGO/term/GO:0045787)) and 'Dna replication' ([GO:0006260](https://www.ebi.ac.uk/QuickGO/term/GO:0006260)), consistent with its role as a key factor in cell division [Link](https://doi.org/10.1074/jbc.m608165200). A major aspect of its function lies in RNA metabolism, with involvement in 'Mrna processing' ([GO:0006397](https://www.ebi.ac.uk/QuickGO/term/GO:0006397)) and 'Rna splicing' ([GO:0008380](https://www.ebi.ac.uk/QuickGO/term/GO:0008380)). This is physically mediated by its localization to nuclear structures like the 'Nucleolus' ([GO:0005730](https://www.ebi.ac.uk/QuickGO/term/GO:0005730)) and 'Cajal body' ([GO:0015030](https://www.ebi.ac.uk/QuickGO/term/GO:0015030)), where it interacts with the SMN protein complex crucial for spliceosome assembly [Link](https://doi.org/10.1038/35070059). At the molecular level, [ZPR1](/details-gene/8882) functions as a 'Zinc ion binding' ([GO:0008270](https://www.ebi.ac.uk/QuickGO/term/GO:0008270)) protein that participates in numerous protein-protein interactions ('Protein binding' ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515))). Its ability to engage with signaling molecules is highlighted by its binding to receptor tyrosine kinases ('Receptor tyrosine kinase binding' ([GO:0030971](https://www.ebi.ac.uk/QuickGO/term/GO:0030971))), such as the epidermal growth factor receptor, thereby connecting it directly to mitogenic signaling pathways [Link](https://doi.org/10.1126/science.272.5269.1797). The gene's role in neurodevelopment is supported by annotations such as 'Axon development' ([GO:0061564](https://www.ebi.ac.uk/QuickGO/term/GO:0061564)) and 'Spinal cord development' ([GO:0021510](https://www.ebi.ac.uk/QuickGO/term/GO:0021510)), which provides a molecular basis for its link to neurological disorders. ## Research Directions The established roles of [ZPR1](/details-gene/8882) in cell cycle control, RNA splicing, and neurodevelopment, combined with its high expression in the immune system, suggest several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high expression across diverse lymphocyte populations and its role in regulating proliferation, dysregulation of [ZPR1](/details-gene/8882) may contribute to the pathology of hematological malignancies by uncoupling cell cycle progression from normal homeostatic controls. 2. The documented interaction between ZPR1 and the SMN protein suggests that [ZPR1](/details-gene/8882) acts as a genetic modifier of Spinal Muscular Atrophy (SMA). Pathogenic variants in [ZPR1](/details-gene/8882) could exacerbate the splicing defects caused by SMN deficiency in motor neurons, thus influencing disease severity [Link](https://doi.org/10.1093/hmg/dds102). **Experimental Approach:** To test the hypothesis that [ZPR1](/details-gene/8882) is a modifier of SMA (Hypothesis 2), a robust experimental model could be developed. One could use CRISPR-Cas9 to introduce a known pathogenic [ZPR1](/details-gene/8882) mutation, such as one identified in the human growth restriction syndrome [Link](https://doi.org/10.1111/cge.13388), into an established mouse model of SMA (e.g., Smn-/-;SMN2). The resulting double-mutant mice could be compared to the parental SMA model mice to assess key disease phenotypes, including motor neuron survival, neuromuscular junction integrity, and overall lifespan. To probe the underlying mechanism, deep RNA-sequencing of spinal cord tissue from these models would allow for a comprehensive analysis of splicing efficiency and could identify specific pre-mRNA targets that are particularly vulnerable to the combined loss of SMN and ZPR1 function. **Therapeutic Potential:** As [ZPR1](/details-gene/8882) is integral to fundamental cellular processes like cell cycle and splicing, systemic inhibition would likely be associated with high toxicity, making it a challenging therapeutic target. However, its role as a potential modifier of SMA presents a more nuanced opportunity. Rather than direct inhibition or activation, a therapeutic strategy could focus on developing small molecules that stabilize the interaction between ZPR1 and the SMN protein complex. Such a compound could potentially enhance the function of the residual SMN protein in SMA patients, thereby ameliorating the downstream splicing defects. This approach would be particularly relevant for patients whose disease severity is influenced by their specific [ZPR1](/details-gene/8882) genetic background.

Genular Protein ID: 3198764847

Symbol: ZPR1_HUMAN

Name: Zinc finger protein ZPR1

UniProtKB Accession Codes:

O75312 Q2TAA0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 37 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9852145

Title: Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells.

PubMed ID: 9852145

DOI: 10.1083/jcb.143.6.1471

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: 8650580

Title: Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor.

PubMed ID: 8650580

DOI: 10.1126/science.272.5269.1797

PubMed ID: 9763455

Title: The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of proliferating cells.

PubMed ID: 9763455

DOI: 10.1091/mbc.9.10.2963

PubMed ID: 11283611

Title: Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein.

PubMed ID: 11283611

DOI: 10.1038/35070059

PubMed ID: 12095920

Title: SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta.

PubMed ID: 12095920

DOI: 10.1093/hmg/11.15.1785

PubMed ID: 17068332

Title: Deficiency of the zinc finger protein ZPR1 causes defects in transcription and cell cycle progression.

PubMed ID: 17068332

DOI: 10.1074/jbc.m608165200

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22422766

Title: The zinc finger protein ZPR1 is a potential modifier of spinal muscular atrophy.

PubMed ID: 22422766

DOI: 10.1093/hmg/dds102

PubMed ID: 29851065

Title: A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys.

PubMed ID: 29851065

DOI: 10.1111/cge.13388

Sequence Information:

  • Length: 459
  • Mass: 50925
  • Checksum: E3DB820F490F2835
  • Sequence:
    • MAASGAVEPG PPGAAVAPSP APAPPPAPDH LFRPISAEDE EQQPTEIESL CMNCYCNGMT 
RLLLTKIPFF REIIVSSFSC EHCGWNNTEI QSAGRIQDQG VRYTLSVRAL EDMNREVVKT 
DSAATRIPEL DFEIPAFSQK GALTTVEGLI TRAISGLEQD QPARRANKDA TAERIDEFIV 
KLKELKQVAS PFTLIIDDPS GNSFVENPHA PQKDDALVIT HYNRTRQQEE MLGLQEEAPA 
EKPEEEDLRN EVLQFSTNCP ECNAPAQTNM KLVQIPHFKE VIIMATNCEN CGHRTNEVKS 
GGAVEPLGTR ITLHITDASD MTRDLLKSET CSVEIPELEF ELGMAVLGGK FTTLEGLLKD 
IRELVTKNPF TLGDSSNPGQ TERLQEFSQK MDQIIEGNMK AHFIMDDPAG NSYLQNVYAP 
EDDPEMKVER YKRTFDQNEE LGLNDMKTEG YEAGLAPQR