Details for: ZNHIT2

Gene ID: 741

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: ZNHIT2

Ensembl ID: ENSG00000174276

Description: zinc finger HIT-type containing 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.79
    rCSI 2.65%
    PRS 99.67
  • multi-ciliated epithelial cell CL0005012
    CSI 3.73
    rCSI 3.72%
    PRS 97.93
  • lung ciliated cell CL1000271
    CSI 3.59
    rCSI 4.16%
    PRS 97.97
  • ciliated epithelial cell CL0000067
    CSI 3.15
    rCSI 2.77%
    PRS 97.31
  • retina horizontal cell CL0000745
    CSI 3.06
    rCSI 4.66%
    PRS 98.38
  • club cell CL0000158
    CSI 2.45
    rCSI 3.58%
    PRS 99.18
  • ciliated cell CL0000064
    CSI 2.4
    rCSI 3.9%
    PRS 97.27
  • deuterosomal cell CL4033044
    CSI 1.36
    rCSI 4.59%
    PRS 96.91
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.14
    rCSI 2.59%
    PRS 97.13

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 [ZNHIT2](/details-gene/741) (Zinc finger HIT-type containing 2) is a protein-coding gene located on chromosome 11q13.1. It encodes a protein characterized by a zinc finger HIT domain, a structure known for metal and protein binding capabilities ([Link](https://doi.org/10.1110/ps.062635107)). Functionally, [ZNHIT2](/details-gene/741) is a crucial component in the assembly of the U5 small nuclear ribonucleoprotein (snRNP), a core element of the spliceosome, through its interaction with the R2TP/Prefoldin-like complex ([Link](https://doi.org/10.1038/ncomms15615)). **Overall**, expression data reveals that [ZNHIT2](/details-gene/741) is a highly significant gene in various types of ciliated epithelial cells, including [multi-ciliated epithelial cells](/details-cell/CL0005012) and [lung ciliated cells](/details-cell/CL1000271), as well as in [plasmacytoid dendritic cells, human](/details-cell/CL0001058), suggesting key roles in both epithelial barrier function and innate immunity. ## Cellular Roles and Expression Landscape The expression profile of [ZNHIT2](/details-gene/741) points towards a specialized function in distinct cell lineages. **Overall**, the gene demonstrates its highest significance in cell types associated with ciliary structures. This includes top rankings in [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 3.73), [lung ciliated cell](/details-cell/CL1000271) (CSI: 3.59), and [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 3.15). The high significance in [deuterosomal cells](/details-cell/CL4033044) (CSI: 1.36), which are precursors to multi-ciliated cells, further suggests a role for [ZNHIT2](/details-gene/741) in the process of ciliogenesis. In parallel, [ZNHIT2](/details-gene/741) is identified as a top marker for [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 3.79), a specialized immune cell type responsible for producing large amounts of type I interferons in response to viral infections. This distinct immunological signature, combined with its prevalence in ciliated cells that form mucosal barriers, suggests [ZNHIT2](/details-gene/741) may operate at the host-pathogen interface, contributing to both physical defense and antiviral immune responses. The gene also shows notable significance in [retina horizontal cells](/details-cell/CL0000745) (CSI: 3.06), indicating a potential, less-characterized role in neuronal cell types of the eye. ## Pathways and Molecular Function The molecular functions attributed to [ZNHIT2](/details-gene/741) are consistent with its known protein interactions and structural domains. Gene Ontology annotations include [metal ion binding](/details-go/GO:0046872) and [protein binding](/details-go/GO:0005515). These fundamental activities enable its primary documented role in cellular machinery. The most critical function of [ZNHIT2](/details-gene/741) is its involvement in the biogenesis of the spliceosome. Research has shown that it directly interacts with RUVBL1/RUVBL2, which are components of the R2TP/Prefoldin-like complex, to facilitate the proper assembly of the U5 snRNP particle ([Link](https://doi.org/10.1038/ncomms15615)). As the spliceosome is responsible for pre-mRNA splicing, a fundamental step in eukaryotic gene expression, [ZNHIT2](/details-gene/741) likely influences the proteome of cells where it is highly expressed by ensuring the fidelity and efficiency of this process. This role in regulating RNA processing may be particularly critical for the complex protein repertoires required for ciliary function and the rapid antiviral response of plasmacytoid dendritic cells. ## Research Directions The specific expression patterns and core molecular function of [ZNHIT2](/details-gene/741) in pre-mRNA splicing regulation suggest several avenues for future investigation. The dual prominence in ciliated epithelial cells and key innate immune cells points to a potentially critical role in mucosal immunology and host defense. ### Proposed Hypotheses: 1. **[ZNHIT2](/details-gene/741) is essential for ciliogenesis and ciliary function.** Given its high expression in a wide array of ciliated cells ([multi-ciliated epithelial cell](/details-cell/CL0005012), [lung ciliated cell](/details-cell/CL1000271)) and their precursors ([deuterosomal cell](/details-cell/CL4033044)), we hypothesize that [ZNHIT2](/details-gene/741) regulates the splicing of specific transcripts that encode essential structural or regulatory components of cilia. Its dysfunction could therefore be implicated in ciliopathies. 2. **[ZNHIT2](/details-gene/741) modulates the type I interferon response in plasmacytoid dendritic cells.** The high significance in [plasmacytoid dendritic cells, human](/details-cell/CL0001058) suggests a specialized role. We hypothesize that [ZNHIT2](/details-gene/741)-mediated splicing is required for the efficient expression of key genes in the viral-sensing and interferon production pathways, such as *TLR7*, *IRF7*, or interferon-alpha genes themselves. ### Key Experiment Proposal: To test the hypothesis that [ZNHIT2](/details-gene/741) is critical for ciliogenesis, an *in vitro* model using human bronchial epithelial cells (HBECs) grown at an air-liquid interface (ALI) to induce differentiation into a ciliated epithelium could be employed. * **Approach:** [ZNHIT2](/details-gene/741) expression would be knocked down using shRNA or knocked out via CRISPR-Cas9 in primary HBECs prior to ALI culture. * **Analysis:** Ciliogenesis and function would be assessed via immunofluorescence microscopy for ciliary markers (e.g., acetylated α-tubulin, IFT88) and high-speed video microscopy to measure ciliary beat frequency. * **Mechanism:** Deep RNA-sequencing of control and [ZNHIT2](/details-gene/741)-deficient cells would be performed to identify global changes in splicing events, with a focus on differential exon usage in genes known to be involved in ciliary assembly and function. ### Therapeutic Potential: As a component of the core spliceosome machinery, [ZNHIT2](/details-gene/741) is likely a poor candidate for direct therapeutic targeting via systemic inhibition, as this would probably lead to widespread cellular toxicity. However, if its role in specific cell types proves to be dependent on unique protein-protein interactions or regulatory mechanisms, these interfaces could offer more targeted therapeutic opportunities. For instance, if its function in pDCs is uniquely critical for certain viral responses, understanding its regulatory network could reveal downstream pathways that are more amenable to therapeutic modulation.

Genular Protein ID: 2822222650

Symbol: ZNHI2_HUMAN

Name: Zinc finger HIT domain-containing protein 2

UniProtKB Accession Codes:

Q9UHR6 Q3SY14 Q8IUV0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 8 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 1 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10602999

Title: Molecular characterization of human and murine c11orf5, a new member of the FAUNA gene cluster.

PubMed ID: 10602999

DOI: 10.1007/s003350010016

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: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 28561026

Title: R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein.

PubMed ID: 28561026

DOI: 10.1038/ncomms15615

PubMed ID: 17656577

Title: Solution structure of the zinc finger HIT domain in protein FON.

PubMed ID: 17656577

DOI: 10.1110/ps.062635107

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 403
  • Mass: 42884
  • Checksum: 2384BF806CC40E71
  • Sequence:
    • MEPAGPCGFC PAGEVQPARY TCPRCNAPYC SLRCYRTHGT CAENFYRDQV LGELRGCSAP 
PSRLASALRR LRQQRETEDE PGEAGLSSGP APGGLSGLWE RLAPGEKAAF ERLLSRGEAG 
RLLPPWRPWW WNRGAGPQLL EELDNAPGSD AAELELAPAR TPPDSVKDAS AAEPAAAERV 
LGDVPGACTP VVPTRIPAIV SLSRGPVSPL VRFQLPNVLF AYAHTLALYH GGDDALLSDF 
CATLLGVSGA LGAQQVFASA EEALQAAAHV LEAGEHPPGP LGTRGAMHEV ARILLGEGPT 
NQKGYTLAAL GDLAQTLGRA RKQAVAREER DHLYRARKKC QFLLAWTNEN EAALTPLALD 
CARAHQAHAV VAEEVAALTG ELERLWGGPV PPAPRTLIEE LPS