Details for: SPAG4

Gene ID: 6676

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: SPAG4

Ensembl ID: ENSG00000061656

Description: sperm associated antigen 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmablast CL0000980
    CSI 4.85
    rCSI 3.82%
    PRS 98.66
  • plasma cell CL0000786
    CSI 4.01
    rCSI 5.25%
    PRS 99.19
  • IgA plasma cell CL0000987
    CSI 3.58
    rCSI 3.66%
    PRS 97.59
  • myofibroblast cell CL0000186
    CSI 3.34
    rCSI 4.63%
    PRS 98.66
  • stem cell CL0000034
    CSI 3.25
    rCSI 3.13%
    PRS 98.91
  • epithelial cell CL0000066
    CSI 3.23
    rCSI 4.97%
    PRS 95.51
  • pancreatic acinar cell CL0002064
    CSI 2.69
    rCSI 3.58%
    PRS 98.95
  • IgG plasma cell CL0000985
    CSI 2.56
    rCSI 3.06%
    PRS 98.59
  • enterocyte CL0000584
    CSI 2.21
    rCSI 3.56%
    PRS 98.17
  • pancreatic stellate cell CL0002410
    CSI 0.73
    rCSI 4.25%
    PRS 99.05

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.

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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 [SPAG4](/details-gene/6676) (Sperm Associated Antigen 4) is a protein-coding gene located on chromosome 20. Originally identified for its role in [spermatogenesis](/details-go/GO:0007283) ([Link](https://pubmed.ncbi.nlm.nih.gov/9691178/)), particularly in maintaining the integrity of the [nuclear envelope](/details-go/GO:0005635) in postmeiotic germ cells ([Link](https://doi.org/10.1371/journal.pone.0120722)), its broader expression profile suggests a more widespread function. Analysis of its expression across diverse cell types reveals high significance in terminally differentiated, antibody-secreting cells of the B cell lineage, such as [plasmablast](/details-cell/CL0000980)s and [plasma cell](/details-cell/CL0000786)s. Furthermore, its notable expression in [myofibroblast cell](/details-cell/CL0000186)s and [epithelial cell](/details-cell/CL0000066)s indicates a general role in providing structural support to cells with high metabolic or mechanical activity. ## Cellular Roles and Expression Landscape **`Overall`**, the expression pattern of [SPAG4](/details-gene/6676) highlights its importance in highly specialized, protein-secreting and structurally active cell types. The most significant signal is observed within the humoral immune system, where [SPAG4](/details-gene/6676) is a top marker for [plasmablast](/details-cell/CL0000980) (CSI: 4.85), [plasma cell](/details-cell/CL0000786) (CSI: 4.01), and specific immunoglobulin-secreting subtypes like [IgA plasma cell](/details-cell/CL0000987) and [IgG plasma cell](/details-cell/CL0000985). This strong association suggests that [SPAG4](/details-gene/6676) is integral to the cellular machinery that supports the massive production and secretion of antibodies. Beyond its role in the immune system, [SPAG4](/details-gene/6676) demonstrates significant expression in cells contributing to tissue structure and function. Its high CSI in [myofibroblast cell](/details-cell/CL0000186) (CSI: 3.34) points to a role in tissue contractility and extracellular matrix deposition. Additionally, its significance in diverse cell types such as [stem cell](/details-cell/CL0000034), [epithelial cell](/details-cell/CL0000066), [pancreatic acinar cell](/details-cell/CL0002064), and [enterocyte](/details-cell/CL0000584) suggests a conserved structural function in cells undergoing differentiation, regeneration, or high-volume secretion. ## Pathways and Molecular Function Functional annotations for [SPAG4](/details-gene/6676) align with a role as a structural and adaptor protein. It is implicated in fundamental processes like [cell differentiation](/details-go/GO:0030154) and its originally defined context, [spermatogenesis](/details-go/GO:0007283). At the molecular level, it is known to participate in [protein binding](/details-go/GO:0005515) and exhibits [structural molecule activity](/details-go/GO:0005198). Its annotated cellular localizations are particularly informative, placing it within the [cytoplasm](/details-go/GO:0005737), [cytoskeleton](/details-go/GO:0005856), and [motile cilium](/details-go/GO:0031514). Critically, research has highlighted its role at the [nuclear envelope](/details-go/GO:0005635) and [nuclear inner membrane](/details-go/GO:0005637), where it is part of a complex required to maintain nuclear integrity in male germ cells ([Link](https://doi.org/10.1371/journal.pone.0120722)). This structural function at the nuclear membrane is consistent with its high expression in [plasma cell](/details-cell/CL0000786)s, which must manage immense transcriptional and translational stress during antibody production. ## Research Directions The widespread significance of [SPAG4](/details-gene/6676) beyond germ cells, particularly in plasma cells and myofibroblasts, opens several avenues for investigation, especially in the context of disease. One study has already suggested [SPAG4](/details-gene/6676) as a potential cancer marker ([Link](https://doi.org/10.1007/s00441-003-0821-2)), a finding that warrants further exploration. **Proposed Hypotheses:** 1. Given its high expression in [plasmablast](/details-cell/CL0000980)s and its established role in maintaining [nuclear envelope](/details-go/GO:0005635) integrity, [SPAG4](/details-gene/6676) is essential for the viability and secretory function of antibody-producing cells. Its depletion is hypothesized to impair immunoglobulin secretion and induce apoptosis in plasma cells, potentially by compromising the structural support needed for their expanded endoplasmic reticulum. 2. The high significance of [SPAG4](/details-gene/6676) in [myofibroblast cell](/details-cell/CL0000186)s suggests it may play a critical role in tissue fibrosis and the tumor microenvironment. It is hypothesized that [SPAG4](/details-gene/6676) contributes to the contractile and matrix-remodeling functions of cancer-associated fibroblasts, thereby facilitating tumor progression and invasion. **Experimental Approach:** To test the first hypothesis regarding the role of [SPAG4](/details-gene/6676) in plasma cell function, one could isolate primary human B-lymphocytes and induce their differentiation into plasma cells *in vitro*. Using a CRISPR-Cas9 or shRNA-based approach to silence [SPAG4](/details-gene/6676) expression during this differentiation, key readouts would include: quantification of immunoglobulin secretion via ELISA, assessment of cell viability and apoptosis rates by flow cytometry, and analysis of cellular ultrastructure—specifically the nuclear envelope and endoplasmic reticulum—using transmission electron microscopy. **Therapeutic Potential:** As an intracellular structural protein, [SPAG4](/details-gene/6676) presents a challenging target for conventional small-molecule inhibitors or antibody-based therapies. However, its high expression in [plasma cell](/details-cell/CL0000786)s could make it a relevant therapeutic target in plasma cell dyscrasias such as multiple myeloma. If its expression is selectively elevated in malignant cells, therapeutic strategies aimed at inhibiting its expression, such as antisense oligonucleotides or siRNA-based delivery systems, could be explored. Disruption of this key structural component would likely compromise the viability of cancer cells that are highly dependent on it, representing a potential pro-apoptotic strategy.

Genular Protein ID: 295195431

Symbol: SPAG4_HUMAN

Name: Sperm-associated antigen 4 protein

UniProtKB Accession Codes:

Q9NPE6 O43648

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 10 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 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14614621

Title: Human sperm associated antigen 4 (SPAG4) is a potential cancer marker.

PubMed ID: 14614621

DOI: 10.1007/s00441-003-0821-2

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 9691178

Title: A novel testis-specific gene, SPAG4, whose product interacts specifically with outer dense fiber protein ODF27, maps to human chromosome 20q11.2.

PubMed ID: 9691178

DOI: 10.1159/000014990

PubMed ID: 25775403

Title: SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells.

PubMed ID: 25775403

DOI: 10.1371/journal.pone.0120722

Sequence Information:

  • Length: 437
  • Mass: 48165
  • Checksum: 5D1E3BCAEEE8B702
  • Sequence:
    • MRRSSRPGSA SSSRKHTPNF FSENSSMSIT SEDSKGLRSA EPGPGEPEGR RARGPSCGEP 
ALSAGVPGGT TWAGSSQQKP APRSHNWQTA CGAATVRGGA SEPTGSPVVS EEPLDLLPTL 
DLRQEMPPPR VFKSFLSLLF QGLSVLLSLA GDVLVSMYRE VCSIRFLFTA VSLLSLFLSA 
FWLGLLYLVS PLENEPKEML TLSEYHERVR SQGQQLQQLQ AELDKLHKEV STVRAANSER 
VAKLVFQRLN EDFVRKPDYA LSSVGASIDL QKTSHDYADR NTAYFWNRFS FWNYARPPTV 
ILEPHVFPGN CWAFEGDQGQ VVIQLPGRVQ LSDITLQHPP PSVEHTGGAN SAPRDFAVFG 
LQVYDETEVS LGKFTFDVEK SEIQTFHLQN DPPAAFPKVK IQILSNWGHP RFTCLYRVRA 
HGVRTSEGAE GSAQGPH

Genular Protein ID: 2760533959

Symbol: A0A7P0Z4G5_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A7P0Z4G5

Database IDs:

ARBA 3 AlphaFoldDB 1 Bgee 1 CTD 1 DisGeNET 1 EMBL 1 Ensembl 2 GO 1 Gene3D 1 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 PANTHER 2 PROSITE 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 3 SMR 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 360
  • Mass: 40398
  • Checksum: 17C3355FD6925588
  • Sequence:
    • MGRKLSAEAS ASEPQLADSL WRGNQPTGSP VVSEEPLDLL PTLDLRQEMP PPRVFKSFLS 
LLFQGLSVLL SLAGDVLVSM YREVCSIRFL FTAVSLLSLF LSAFWLGLLY LVSPLENEPK 
EMLTLSEYHE RVRSQGQQLQ QLQAELDKLH KEVSTVRAAN SERVAKLVFQ RLNEDFVRKP 
DYALSSVGAS IDLQKTSHDY ADRNTAYFWN RFSFWNYARP PTVILEPHVF PGNCWAFEGD 
QGQVVIQLPG RVQLSDITLQ HPPPSVEHTG GANSAPRDFA VFGLQVYDET EVSLGKFTFD 
VEKSEIQTFH LQNDPPAAFP KVKIQILSNW GHPRFTCLYR VRAHGVRTSE GAEGSAQGPH