Details for: ZPBP

Gene ID: 11055

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: ZPBP

Ensembl ID: ENSG00000042813

Description: zona pellucida binding protein

Cell Significance Landscape

Associated with

Significant Cells

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

  • retinal bipolar neuron CL0000748
    CSI 32.65
    rCSI 61.15%
    PRS 99
  • retinal rod cell CL0000604
    CSI 14.99
    rCSI 26.42%
    PRS 98.99
  • S cone cell CL0003050
    CSI 12.71
    rCSI 55.87%
    PRS 99.4
  • retinal ganglion cell CL0000740
    CSI 11.58
    rCSI 25.57%
    PRS 99
  • diffuse bipolar 3b cell CL4033030
    CSI 10.49
    rCSI 69.65%
    PRS 98.75
  • diffuse bipolar 3a cell CL4033029
    CSI 10.13
    rCSI 68.95%
    PRS 98.64
  • diffuse bipolar 2 cell CL4033028
    CSI 9.1
    rCSI 70.53%
    PRS 98.81
  • invaginating midget bipolar cell CL4033034
    CSI 8.36
    rCSI 49.4%
    PRS 98.56
  • cardiac muscle cell CL0000746
    CSI 8.3
    rCSI 11.91%
    PRS 98.91
  • flat midget bipolar cell CL4033033
    CSI 8.18
    rCSI 58.51%
    PRS 98.54
  • ependymal cell CL0000065
    CSI 7.73
    rCSI 15.69%
    PRS 97.57
  • Mueller cell CL0000636
    CSI 7.54
    rCSI 17.21%
    PRS 99.26
  • retinal cone cell CL0000573
    CSI 7.52
    rCSI 12.1%
    PRS 98.75
  • OFFx cell CL4033036
    CSI 7.19
    rCSI 33.85%
    PRS 98.53
  • diffuse bipolar 1 cell CL4033027
    CSI 7.17
    rCSI 53.91%
    PRS 98.29
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 6.57
    rCSI 8.17%
    PRS 98.89
  • VIP GABAergic cortical interneuron CL4023016
    CSI 5.39
    rCSI 6.44%
    PRS 98.98
  • diffuse bipolar 4 cell CL4033031
    CSI 5.19
    rCSI 59.45%
    PRS 97.49
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 4.73
    rCSI 7.95%
    PRS 99.02
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.46
    rCSI 13.94%
    PRS 99.14
  • OFF-bipolar cell CL0000750
    CSI 4.43
    rCSI 6.06%
    PRS 99.47
  • GABAergic amacrine cell CL4030027
    CSI 4.32
    rCSI 14.78%
    PRS 98.68
  • sncg GABAergic cortical interneuron CL4023015
    CSI 4.25
    rCSI 6.83%
    PRS 98.88
  • amacrine cell CL0000561
    CSI 3.34
    rCSI 9.69%
    PRS 99.18
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.06
    rCSI 19.13%
    PRS 98.99
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.99
    rCSI 5.28%
    PRS 99
  • ON midget ganglion cell CL4033046
    CSI 2.76
    rCSI 56.15%
    PRS 98.99
  • OFF midget ganglion cell CL4033047
    CSI 2.7
    rCSI 54.92%
    PRS 99.04
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.35
    rCSI 8.46%
    PRS 98.79
  • glial cell CL0000125
    CSI 2.32
    rCSI 8.84%
    PRS 98.89
  • diffuse bipolar 6 cell CL4033032
    CSI 2.05
    rCSI 10.76%
    PRS 98.19
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.95
    rCSI 6.1%
    PRS 98.99

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 [ZPBP](/details-gene/11055) (Zona Pellucida Binding Protein) is a protein-coding gene located on chromosome 7. It is canonically known for its essential role in male fertility, specifically in the binding of sperm to the oocyte's zona pellucida and in the proper formation of the acrosome. Functional annotations strongly link [ZPBP](/details-gene/11055) to processes like '[acrosome assembly](/details-go/GO:0001675)' and '[binding of sperm to zona pellucida](/details-go/GO:0007339)'. However, expression profiling data reveals its most significant expression is not in reproductive tissues but rather in various neuronal cell types of the retina, including the [retinal bipolar neuron](/details-cell/CL0000748) and [retinal rod cell](/details-cell/CL0000604). This suggests a potential and previously uncharacterized secondary function for [ZPBP](/details-gene/11055) in the central nervous system, particularly in the intricate cellular architecture of the eye. ## Cellular Roles and Expression Landscape The expression landscape of [ZPBP](/details-gene/11055) presents a striking dichotomy between its established function and observed cellular significance. **Overall**, the gene demonstrates its highest significance in a range of specialized neurons and glial cells within the retina. It is the top marker for [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 32.65) and shows high significance in photoreceptor cells such as the [retinal rod cell](/details-cell/CL0000604) (CSI: 14.99) and [S cone cell](/details-cell/CL0003050) (CSI: 12.71). Its prominence extends to other retinal cell types including the [retinal ganglion cell](/details-cell/CL0000740) and [Mueller cell](/details-cell/CL0000636). This consistent and high-level significance across multiple, functionally related retinal cell types strongly suggests a novel role in retinal biology, which may be related to synaptic organization, cell adhesion, or maintenance of the extracellular matrix. This expression pattern contrasts sharply with its well-documented role in sperm development and function. ## Pathways and Molecular Function The known molecular functions of [ZPBP](/details-gene/11055) are exclusively related to sexual reproduction. Gene Ontology annotations place it within the '[acrosomal vesicle](/details-go/GO:0001669)' and the '[zona pellucida receptor complex](/details-go/GO:0002199)'. Its involvement in '[acrosome assembly](/details-go/GO:0001675)' is critical for creating a functional sperm head, and its role in '[binding of sperm to zona pellucida](/details-go/GO:0007339)' is a key step in fertilization. Research has demonstrated that loss of [ZPBP](/details-gene/11055) disrupts acrosome biogenesis and sperm morphology, leading to infertility ([Link](https://doi.org/10.1128/mcb.01029-07)). Furthermore, mutations in the human [ZPBP](/details-gene/11055) gene have been directly associated with abnormal sperm head morphology (globozoospermia) in infertile men ([Link](https://doi.org/10.1093/molehr/gar057); [Link](https://doi.org/10.1093/humrep/dez246)). The stark contrast between this well-defined reproductive function and its high expression in retinal neurons points to a significant gap in the understanding of this gene's complete biological scope. ## Research Directions The marked discrepancy between the canonical reproductive function of [ZPBP](/details-gene/11055) and its highly specific expression profile in retinal neurons is a compelling area for future investigation. This suggests the protein may be a moonlighting protein with distinct functions in disparate biological systems. Based on the available data, several testable hypotheses can be proposed: 1. [ZPBP](/details-gene/11055) plays a direct role in the structural integrity or synaptic connectivity of the retina. Given its function as a binding protein, it may mediate cell-cell or cell-matrix interactions between photoreceptors, bipolar cells, and ganglion cells, contributing to the precise layering and function of the retinal architecture. 2. The expression of [ZPBP](/details-gene/11055) in the retina is related to a shared molecular mechanism between photoreceptor outer segment development and acrosome biogenesis. Both processes involve extensive membrane remodeling and the formation of specialized cellular protrusions, and [ZPBP](/details-gene/11055) may be a component of this shared machinery. A key experiment to test the first hypothesis would be to characterize the functional consequence of [ZPBP](/details-gene/11055) loss in the retina. This could be achieved by generating a retina-specific conditional knockout of *Zpbp* in a mouse model. The retinal structure and function in these mice could be assessed using immunohistochemistry to examine retinal layers, and electroretinography (ERG) to measure the electrical responses of photoreceptors and other retinal cells to light stimuli. Any observed defects in retinal lamination or ERG waveforms would provide strong evidence for a critical role of [ZPBP](/details-gene/11055) in visual function. Given that mutations in [ZPBP](/details-gene/11055) are linked to male infertility, its therapeutic potential is primarily in the realm of diagnostics. Screening for mutations in this gene could be a valuable tool for identifying the genetic causes of certain forms of male infertility, such as globozoospermia. Its potential as a therapeutic target in retinal disease is currently speculative but could emerge if its newly suggested role in retinal biology is confirmed and linked to a specific pathology.

Genular Protein ID: 3725165528

Symbol: ZPBP1_HUMAN

Name: Zona pellucida-binding protein 1

UniProtKB Accession Codes:

Q9BS86 A4D253 C9JPU1 Q15941 Q75KX9 Q75MI3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 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 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 9378618

Title: Molecules involved in mammalian sperm-egg interaction.

PubMed ID: 9378618

DOI: 10.1016/s0074-7696(08)62231-7

PubMed ID: 17664285

Title: Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis.

PubMed ID: 17664285

DOI: 10.1128/mcb.01029-07

PubMed ID: 21911476

Title: Association of mutations in the zona pellucida binding protein 1 (ZPBP1) gene with abnormal sperm head morphology in infertile men.

PubMed ID: 21911476

DOI: 10.1093/molehr/gar057

PubMed ID: 31985809

Title: Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia.

PubMed ID: 31985809

DOI: 10.1093/humrep/dez246

Sequence Information:

  • Length: 351
  • Mass: 40142
  • Checksum: 8B57027FBE12E7DB
  • Sequence:
    • MEAFALGPAR RGRRRTRAAG SLLSRAAILL FISAFLVRVP SSVGHLVRLP RAFRLTKDSV 
KIVGSTSFPV KAYVMLHQKS PHVLCVTQQL RNAELIDPSF QWYGPKGKVV SVENRTAQIT 
STGSLVFQNF EESMSGIYTC FLEYKPTVEE IVKRLQLKYA IYAYREPHYY YQFTARYHAA 
PCNSIYNISF EKKLLQILSK LLLDLSCEIS LLKSECHRVK MQRAGLQNEL FFAFSVSSLD 
TEKGPKRCTD HNCEPYKRLF KAKNLIERFF NQQVEILGRR AEQLPQIYYI EGTLQMVWIN 
RCFPGYGMNV QQHPKCPECC VICSPGSYNP RDGIHCLQCN SSLVYGAKTC L