Details for: ZNF365

Gene ID: 22891

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: ZNF365

Ensembl ID: ENSG00000138311

Description: zinc finger protein 365

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 13.36
    rCSI 32.48%
    PRS 93.23
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 12.14
    rCSI 22.05%
    PRS 95.46
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 8.76
    rCSI 14.7%
    PRS 94.82
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 8.63
    rCSI 18.73%
    PRS 92.51
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 7.11
    rCSI 25.59%
    PRS 93.58
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 5.52
    rCSI 32.5%
    PRS 94.34
  • L6b glutamatergic cortical neuron CL4023038
    CSI 5.45
    rCSI 17.03%
    PRS 94.87
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 4.97
    rCSI 16.32%
    PRS 92.84
  • inhibitory interneuron CL0000498
    CSI 4.92
    rCSI 11.37%
    PRS 94.9
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.42
    rCSI 5.49%
    PRS 93.66
  • rod bipolar cell CL0000751
    CSI 4.33
    rCSI 7.78%
    PRS 96.17
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.12
    rCSI 4.92%
    PRS 94.6
  • cerebral cortex neuron CL0010012
    CSI 4.04
    rCSI 16.47%
    PRS 94.43
  • retinal bipolar neuron CL0000748
    CSI 3.94
    rCSI 7.38%
    PRS 95.16
  • glutamatergic neuron CL0000679
    CSI 3.38
    rCSI 6.95%
    PRS 92.31
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.75
    rCSI 8.59%
    PRS 95.28
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.71
    rCSI 3.49%
    PRS 95.14
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.52
    rCSI 5.66%
    PRS 94.58
  • oligodendrocyte precursor cell CL0002453
    CSI 2.19
    rCSI 4.82%
    PRS 89.98
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.13
    rCSI 8.06%
    PRS 94.13
  • direct pathway medium spiny neuron CL4023026
    CSI 1.79
    rCSI 42.79%
    PRS 92.57
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.77
    rCSI 42.65%
    PRS 92.2
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.64
    rCSI 2.89%
    PRS 94.56
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.62
    rCSI 3.88%
    PRS 93.54

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)

Loading network (please wait)...

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 [ZNF365](/details-gene/22891) is a protein-coding gene that encodes Zinc Finger Protein 365. This protein plays a multifaceted role in fundamental cellular processes, with significant functions in maintaining genome integrity and regulating neuronal development. Functional annotations strongly link [ZNF365](/details-gene/22891) to DNA repair, telomere maintenance, and the regulation of the cell cycle, particularly mitotic cytokinesis ([Link](https://pubmed.ncbi.nlm.nih.gov/16617106/)). Concurrently, it is implicated in the morphogenesis of dendrites and dendritic spines, the regulation of neuron projection, and oligodendrocyte differentiation. **Overall**, expression data reveals that [ZNF365](/details-gene/22891) is a highly significant gene within the central nervous system, showing prominent expression in various neuronal subtypes, including [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040), and in glial precursors like the [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059), underscoring its dual importance in neural function and development. ## Cellular Roles and Expression Landscape The expression profile of [ZNF365](/details-gene/22891) firmly establishes it as a key gene in the mammalian central nervous system. In the **Overall** context, it demonstrates the highest significance in a broad range of neuronal and glial cell populations. * **Glutamatergic Neurons:** The gene shows its most significant expression in several types of excitatory neurons, including [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 13.36), [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059) (CSI: 8.63), and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 7.11). This pattern suggests a crucial role in the function or maintenance of cortical projection neurons. * **Inhibitory Interneurons:** [ZNF365](/details-gene/22891) is also significantly expressed in inhibitory neuron populations, such as the [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 8.76) and the general [inhibitory interneuron](/details-cell/CL0000498) class (CSI: 4.92), indicating its importance extends to the regulation of cortical circuitry. * **Glial Cells:** A notable finding is the high significance of [ZNF365](/details-gene/22891) in [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) cells (CSI: 12.14). This is consistent with its annotated function in the positive regulation of oligodendrocyte differentiation and points towards a role in myelination processes. * **Retinal Neurons:** The gene's activity also extends to the retina, with significant expression in [rod bipolar cell](/details-cell/CL0000751) (CSI: 4.33) and the broader [retinal bipolar neuron](/details-cell/CL0000748) category (CSI: 3.94). Collectively, the expression landscape highlights [ZNF365](/details-gene/22891) as a gene with widespread importance across diverse neuronal and glial lineages, likely involved in processes common to these cell types, such as morphological development and genomic maintenance. ## Pathways and Molecular Function Functional annotations for [ZNF365](/details-gene/22891) reveal a dual concentration of roles in neuronal morphogenesis and genome stability. * **Neuronal Development and Function:** [ZNF365](/details-gene/22891) is involved in multiple aspects of neuronal architecture, including [dendrite arborization](/details-cell/GO:0140059), [dendritic spine morphogenesis](/details-cell/GO:0060997), and the general [regulation of neuron projection development](/details-cell/GO:0010975). Its interaction with the schizophrenia-associated protein DISC1 has been shown to modulate neurite outgrowth ([Link](https://doi.org/10.1038/sj.mp.4001945)). This is consistent with its high expression across numerous neuron subtypes. Furthermore, its role in the [positive regulation of oligodendrocyte differentiation](/details-cell/GO:0048714) aligns with its high significance in oligodendrocyte precursors. * **Genome Integrity and Cell Cycle:** A critical aspect of [ZNF365](/details-gene/22891) function is its role in maintaining genomic stability. It is essential for the proper execution of [mitotic cytokinesis](/details-cell/GO:0000281) and localizes to the [centrosome](/details-cell/GO:0005813) ([Link](https://doi.org/10.1073/pnas.0601682103)). Research indicates it promotes the stability of fragile sites and is involved in [telomere maintenance](/details-cell/GO:0000723) ([Link](https://doi.org/10.1158/2159-8290.cd-12-0536)). Additionally, it contributes to DNA damage response through the [regulation of double-strand break repair via homologous recombination](/details-cell/GO:0010569) and helps manage replication stress by aiding in the recovery of stalled replication forks ([Link](https://doi.org/10.4161/cc.25882)). * **Molecular Interactions:** At the molecular level, [ZNF365](/details-gene/22891) exhibits [protein binding](/details-cell/GO:0005515) and [identical protein binding](/details-cell/GO:0042802) capabilities, including [protein homodimerization activity](/details-cell/GO:0042803), suggesting it may function as part of larger protein complexes to execute its functions. ## Research Directions The dual role of [ZNF365](/details-gene/22891) in both nervous system development and fundamental genome maintenance processes presents several intriguing avenues for future research. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its roles in both cell division and neuronal development, [ZNF365](/details-gene/22891) may function as a critical regulatory node that couples the final cell cycle exit of neuronal precursors with the initiation of terminal differentiation and dendritic arborization. Its dysregulation could lead to aberrant cell cycle re-entry in post-mitotic neurons, a process implicated in neurodegeneration. 2. **Hypothesis 2:** The high significance of [ZNF365](/details-gene/22891) in [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) cells suggests it is a key factor for successful myelination. We hypothesize that [ZNF365](/details-gene/22891) ensures the genomic stability of these rapidly dividing precursors, and its function is essential to resolve replication stress before they differentiate into mature, myelinating oligodendrocytes. ### Experimental Approach: To test the second hypothesis, one could employ a conditional knockout or CRISPR-Cas9-mediated inactivation of [ZNF365](/details-gene/22891) in primary rodent oligodendrocyte precursor cells (OPCs). These modified OPCs would then be cultured in differentiation-promoting media. The experimental readout would involve: * **Assessing Differentiation:** Quantifying the expression of mature oligodendrocyte markers (e.g., MBP, PLP1, MOG) using qPCR and immunocytochemistry. * **Evaluating Genomic Instability:** Using assays like the comet assay or staining for gamma-H2AX foci to measure DNA damage in both precursor and differentiating cells. * **Analyzing Proliferation:** Measuring cell proliferation rates via BrdU or Ki67 staining to determine if loss of [ZNF365](/details-gene/22891) affects the proliferative capacity of OPCs. This approach would clarify the specific requirement of [ZNF365](/details-gene/22891) for the transition from a proliferative precursor to a differentiated, post-mitotic glial cell. ### Therapeutic Potential: The function of [ZNF365](/details-gene/22891) in DNA repair and cell cycle control makes it a potential factor in CNS pathologies. In the context of cancers like glioblastoma, which involve uncontrolled cell division and genomic instability, overexpression of [ZNF365](/details-gene/22891) could contribute to tumor cell survival. Therefore, it could represent a potential therapeutic target for **inhibition** to sensitize cancer cells to DNA-damaging agents. Conversely, in demyelinating diseases such as multiple sclerosis, where promoting oligodendrocyte differentiation and survival is a therapeutic goal, strategies to modulate or enhance [ZNF365](/details-gene/22891) activity could be explored, although this remains highly speculative. Its early association with uric acid nephrolithiasis also suggests potential roles outside the CNS that warrant further investigation ([Link](https://doi.org/10.1086/375628)).

Genular Protein ID: 2146347579

Symbol: ZN365_HUMAN

Name: Protein ZNF365

UniProtKB Accession Codes:

Q70YC5 A8K0F0 O94930 Q05D75 Q5HYE6 Q68SG8 Q6NSK2 Q6P9D4 Q70YC6 Q70YC7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 2 ExpressionAtlas 1 GO 13 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 3 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12740763

Title: Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate.

PubMed ID: 12740763

DOI: 10.1086/375628

PubMed ID: 10048485

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

PubMed ID: 10048485

DOI: 10.1093/dnares/5.6.355

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: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 15363853

Title: Emergence of talanin protein associated with human uric acid nephrolithiasis in the hominidae lineage.

PubMed ID: 15363853

DOI: 10.1016/j.gene.2004.06.030

PubMed ID: 16682949

Title: Centrosomal proteins Nde1 and Su48 form a complex regulated by phosphorylation.

PubMed ID: 16682949

DOI: 10.1038/sj.onc.1209637

PubMed ID: 16617106

Title: Characterization of Su48, a centrosome protein essential for cell division.

PubMed ID: 16617106

DOI: 10.1073/pnas.0601682103

PubMed ID: 17389905

Title: A novel DISC1-interacting partner DISC1-binding zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth.

PubMed ID: 17389905

DOI: 10.1038/sj.mp.4001945

PubMed ID: 23776040

Title: ZNF365 promotes stability of fragile sites and telomeres.

PubMed ID: 23776040

DOI: 10.1158/2159-8290.cd-12-0536

PubMed ID: 23966166

Title: ZNF365 promotes stalled replication forks recovery to maintain genome stability.

PubMed ID: 23966166

DOI: 10.4161/cc.25882

Sequence Information:

  • Length: 407
  • Mass: 46542
  • Checksum: CC3C25AF6A753E64
  • Sequence:
    • MQQKAFEESR YPWQESFENV AVCLPLRCPR CGDHTRFRSL SSLRAHLEFS HSYEERTLLT 
KCSLFPSLKD TDLVTSSELL KPGKLQSSGN VVKQKPSYVN LYSISHEHSK DRKPFEVVAE 
RPVSYVQTYT AMDLHADSLD GTRSGPGLPT SDTKASFEAH VREKFNRMVE AVDRTIEKRI 
DKLTKELAQK TAELLEVRAA FVQLTQKKQE VQRRERALNR QVDVAVEMIA VLRQRLTESE 
EELLRKEEEV VTFNHFLEAA AEKEVQGKAR LQDFIENLLQ RVELAEKQLE YYQSQQASGF 
VRDLSGHVLT DISSNRKPKC LSRGHPHSVC NHPDLKAHFH PKGRNHLKKA KDDRASMQPA 
KAIHEQAESS RDLCRPPKKG ELLGFGRKGN IRPKMAKKKP TAIVNII