Details for: DZIP1L

Gene ID: 199221

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: DZIP1L

Ensembl ID: ENSG00000158163

Description: DAZ interacting zinc finger protein 1 like

Cell Significance Landscape

Associated with

Significant Cells

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

  • ciliated cell CL0000064
    CSI 5.72
    rCSI 9.27%
    PRS 95.62
  • squamous epithelial cell CL0000076
    CSI 5.48
    rCSI 13.02%
    PRS 95.76
  • ciliated epithelial cell CL0000067
    CSI 4.41
    rCSI 3.88%
    PRS 95.26
  • lung ciliated cell CL1000271
    CSI 3.78
    rCSI 4.38%
    PRS 96.59
  • multi-ciliated epithelial cell CL0005012
    CSI 3.66
    rCSI 3.65%
    PRS 96.27
  • deuterosomal cell CL4033044
    CSI 3.59
    rCSI 12.14%
    PRS 95.22
  • ependymal cell CL0000065
    CSI 3.34
    rCSI 6.79%
    PRS 91.65
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.22
    rCSI 8.17%
    PRS 97.15
  • parietal epithelial cell CL1000452
    CSI 3.15
    rCSI 8.42%
    PRS 97.43
  • hepatic stellate cell CL0000632
    CSI 3.08
    rCSI 11.53%
    PRS 97.58
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.76
    rCSI 6.29%
    PRS 95.24
  • choroid plexus epithelial cell CL0000706
    CSI 2.64
    rCSI 4.32%
    PRS 96.61
  • fibroblast of cardiac tissue CL0002548
    CSI 2.57
    rCSI 12.33%
    PRS 98.65
  • chondrocyte CL0000138
    CSI 2.33
    rCSI 3.7%
    PRS 96.89
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.6
    rCSI 2.69%
    PRS 95.38
  • retinal ganglion cell CL0000740
    CSI 1.29
    rCSI 2.85%
    PRS 94.96
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.29
    rCSI 3.12%
    PRS 93.9

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 [DZIP1L](/details-gene/199221) (DAZ interacting zinc finger protein 1 like) is a protein-coding gene located on chromosome 3q22.3. It plays a critical role in the formation and function of cilia, specifically in the assembly of the ciliary transition zone. Consistent with this function, [DZIP1L](/details-gene/199221) shows highly significant expression in a variety of ciliated cell types, including those in the respiratory and reproductive tracts, the brain, and the kidneys. Functionally, it is involved in fundamental biological processes such as the [Smoothened signaling pathway](/details-go/GO:0007224), and mutations in the gene are causally linked to autosomal recessive polycystic kidney disease, highlighting its importance in human health ([Link](https://doi.org/10.1038/ng.3871)). ## Cellular Roles and Expression Landscape The expression profile of [DZIP1L](/details-gene/199221) underscores its specialized function in ciliated tissues. **Overall**, the gene exhibits its highest significance in cell types characterized by the presence of cilia. These include [ciliated cell](/details-cell/CL0000064) (CSI: 5.72), [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 4.41), [lung ciliated cell](/details-cell/CL1000271) (CSI: 3.78), and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 3.66). Its high significance in [deuterosomal cell](/details-cell/CL4033044) (CSI: 3.59), a progenitor of multi-ciliated cells, suggests a role in the early stages of ciliogenesis. Beyond the respiratory epithelium, [DZIP1L](/details-gene/199221) is also a key marker in other ciliated cell populations, such as [ependymal cell](/details-cell/CL0000065) (CSI: 3.34) lining the brain ventricles and [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 2.64), which are crucial for cerebrospinal fluid circulation. Its notable significance in [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 3.22) is clinically relevant, as primary cilia in these cells are vital for sensing fluid flow and maintaining tubular architecture. The broad but specific expression pattern across these functionally diverse, yet structurally similar, cell types establishes [DZIP1L](/details-gene/199221) as a core component of the molecular machinery required for building and maintaining cilia. ## Pathways and Molecular Function The functional annotations for [DZIP1L](/details-gene/199221) align precisely with its cellular expression profile. The gene product is a key component of the [ciliary basal body](/details-go/GO:0036064) and is integral to [ciliary transition zone assembly](/details-go/GO:1905349), a gatekeeping structure that controls protein entry and exit from the cilium. This localization is fundamental to its role in the broader process of [cilium assembly](/details-go/GO:0060271). Furthermore, [DZIP1L](/details-gene/199221) is implicated in critical signaling pathways that rely on intact cilia. It participates in the [Smoothened signaling pathway](/details-go/GO:0007224), which is a component of the Hedgehog signaling cascade essential for embryonic development, including [neural tube patterning](/details-go/GO:0021532) and [floor plate development](/details-go/GO:0033504). Research has shown that related zinc finger proteins impact Hedgehog signaling by promoting ciliogenesis, suggesting a conserved mechanism of action for [DZIP1L](/details-gene/199221) ([Link](https://doi.org/10.1016/j.ydbio.2009.10.025)). Its annotated molecular functions include [protein binding](/details-go/GO:0005515) and [metal ion binding](/details-go/GO:0046872), consistent with its role as a zinc-finger protein that likely scaffolds other proteins at the ciliary base. ## Research Directions The established link between loss-of-function mutations in [DZIP1L](/details-gene/199221) and autosomal recessive polycystic kidney disease (ARPKD) provides a clear path for future investigation ([Link](https://doi.org/10.1038/ng.3871)). Research should focus on elucidating the precise molecular mechanisms by which its dysfunction in renal cilia leads to cystogenesis. **Proposed Hypotheses:** 1. Disease-causing mutations in [DZIP1L](/details-gene/199221) specifically disrupt its interaction with key transition zone proteins (e.g., CEP290, NPHP proteins) in [kidney connecting tubule epithelial cell](/details-cell/CL1000768), leading to aberrant protein composition within the primary cilium, impaired flow sensing, and dysregulated planar cell polarity, ultimately driving cyst formation. 2. Beyond the kidney, pathogenic variants in [DZIP1L](/details-gene/199221) may cause a broader, sub-clinical ciliopathy spectrum. Incomplete penetrance or variable expressivity could result in subtle defects in tissues rich in motile cilia, such as the respiratory tract ([lung ciliated cell](/details-cell/CL1000271)) or brain ([ependymal cell](/details-cell/CL0000065)), potentially contributing to conditions like chronic sinusitis or hydrocephalus in affected families. **Experimental Approach:** To test the first hypothesis, patient-specific missense mutations could be introduced into the endogenous [DZIP1L](/details-gene/199221) locus in a human kidney organoid model derived from induced pluripotent stem cells (iPSCs) using CRISPR-Cas9 base editing. The resulting organoids could be assessed for defects in ciliogenesis, ciliary length, and transition zone ultrastructure via super-resolution microscopy and transmission electron microscopy. Proximity-dependent biotinylation (BioID) followed by mass spectrometry could be performed on wild-type and mutant DZIP1L to identify specific protein-protein interactions that are lost or gained due to the mutation, thereby revealing the downstream pathways that lead to cystogenesis. **Therapeutic Potential:** As ARPKD caused by [DZIP1L](/details-gene/199221) mutations is a loss-of-function disorder, the primary therapeutic strategy would be functional restoration rather than inhibition. The gene represents a promising candidate for gene replacement therapy. An adeno-associated virus (AAV) vector engineered to deliver a functional copy of the [DZIP1L](/details-gene/199221) cDNA, potentially under the control of a kidney-specific promoter, could be investigated as a means to restore proper ciliary function in renal epithelial cells. Significant challenges related to targeted delivery to the kidney and long-term expression would need to be overcome, but this approach holds potential for correcting the root cause of the disease.

Genular Protein ID: 151070068

Symbol: DZI1L_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8IYY4 C9JUG5 Q96M38

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 12 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

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: 19852954

Title: The Zn finger protein Iguana impacts Hedgehog signaling by promoting ciliogenesis.

PubMed ID: 19852954

DOI: 10.1016/j.ydbio.2009.10.025

PubMed ID: 28530676

Title: Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.

PubMed ID: 28530676

DOI: 10.1038/ng.3871

Sequence Information:

  • Length: 767
  • Mass: 86848
  • Checksum: B491D287A667CCB9
  • Sequence:
    • MQSPAATAEG LSGPLFGAYT FPTFKFQPRH DSMDWRRIST LDVDRVAREL DVATLQENIA 
GITFCNLDRE VCSRCGQPVD PALLKVLRLA QLIIEYLLHC QDCLSASVAQ LEARLQTSLG 
QQQRGQQELG RQADELKGVR EESRRRRKMI STLQQLLMQT GTHSYHTCHL CDKTFMNATF 
LRGHIQRRHA GVAEGGKQKK QEQPVEEVLE ELRAKLKWTQ GELEAQREAE RQRQLQEAEL 
IHQREIEAKK EFDKWKEQEW TKLYGEIDKL KKLFWDEFKN VAKQNSTLEE KLRALQSHSV 
MESKLGSLRD EESEEWLRQA RELQALREKT EIQKTEWKRK VKELHEEHMA EKKELQEENQ 
RLQASLSQDQ KKAAAQSQCQ ISTLRAQLQE QARIIASQEE MIQSLSLRKV EGIHKVPKAV 
DTEEDSPEEE MEDSQDEQHK VLAALRRNPT LLKHFRPILE DTLEEKLESM GIRKDAKGIS 
IQTLRHLESL LRVQREQKAR KFSEFLSLRG KLVKEVTSRA KERQENGAVV SQPDGQPSVK 
SQQSTLVTRE AQPKTRTLQV ALPSTPAEPP PPTRQSHGSH GSSLTQVSAP APRPGLHGPS 
STPPSSGPGM STPPFSSEED SEGDRVQRVS LQPPKVPSRM VPRPKDDWDW SDTETSEENA 
QPPGQGSGTL VQSMVKNLEK QLEAPAKKPA GGVSLFFMPN AGPQRAATPG RKPQLSEDES 
DLEISSLEDL PLDLDQREKP KPLSRSKLPE KFGTGPQSSG QPRVPAW