Details for: SPATA18

Gene ID: 132671

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: SPATA18

Ensembl ID: ENSG00000163071

Description: spermatogenesis associated 18

Cell Significance Landscape

Associated with

Significant Cells

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

  • multi-ciliated epithelial cell CL0005012
    CSI 9.62
    rCSI 9.6%
    PRS 98.29
  • lung ciliated cell CL1000271
    CSI 7.82
    rCSI 9.04%
    PRS 98.35
  • ciliated epithelial cell CL0000067
    CSI 7.13
    rCSI 6.27%
    PRS 97.75
  • ependymal cell CL0000065
    CSI 6.69
    rCSI 13.57%
    PRS 95.55
  • ciliated cell CL0000064
    CSI 5.91
    rCSI 9.57%
    PRS 97.66
  • choroid plexus epithelial cell CL0000706
    CSI 5.28
    rCSI 8.65%
    PRS 98.13
  • secretory cell CL0000151
    CSI 4.78
    rCSI 4.99%
    PRS 99.24
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.13
    rCSI 9.41%
    PRS 97.53
  • nasal mucosa goblet cell CL0002480
    CSI 3.7
    rCSI 4.29%
    PRS 98.86
  • squamous epithelial cell CL0000076
    CSI 2.75
    rCSI 6.52%
    PRS 97.57
  • deuterosomal cell CL4033044
    CSI 2.65
    rCSI 8.96%
    PRS 97.25
  • podocyte CL0000653
    CSI 1.04
    rCSI 4.6%
    PRS 99.14

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [SPATA18](/details-gene/132671), or Spermatogenesis Associated 18, encodes a protein also known as Mieap (Mitochondria-eating protein) that plays a critical role in cellular quality control. The gene is located on chromosome 4q12. Functionally, [SPATA18](/details-gene/132671) is a key regulator of mitophagy, the process responsible for the selective degradation of damaged or superfluous mitochondria ([Link](https://doi.org/10.1371/journal.pone.0016060)). Its expression is transcriptionally regulated by the tumor suppressors p53 and p63, linking it directly to cellular stress and DNA damage responses ([Link](https://doi.org/10.1128/mcb.01072-10)). **Overall**, expression analysis reveals that [SPATA18](/details-gene/132671) is most significantly expressed in various types of ciliated and secretory epithelial cells, such as `[multi-ciliated epithelial cell](/details-cell/CL0005012)` and `[lung ciliated cell](/details-cell/CL1000271)`, suggesting a vital role in maintaining mitochondrial health in cells with high energy demands and metabolic activity. ## Cellular Roles and Expression Landscape The expression profile of [SPATA18](/details-gene/132671) points to a highly specialized function in epithelial tissues, particularly those characterized by motile cilia. **Overall**, the gene shows the highest significance in a range of ciliated cell types, including `[multi-ciliated epithelial cell](/details-cell/CL0005012)` (CSI: 9.62), `[lung ciliated cell](/details-cell/CL1000271)` (CSI: 7.82), `[ciliated epithelial cell](/details-cell/CL0000067)` (CSI: 7.13), and `[ependymal cell](/details-cell/CL0000065)` (CSI: 6.69). These cells require substantial and continuous energy production to power ciliary beating for functions like mucociliary clearance in the airways or cerebrospinal fluid circulation in the brain. The high significance of [SPATA18](/details-gene/132671) in these cells is consistent with a critical need for robust mitochondrial quality control to manage the oxidative stress and turnover associated with high ATP production. Beyond ciliated cells, [SPATA18](/details-gene/132671) is also a significant marker in other metabolically active epithelial and secretory cells, such as `[choroid plexus epithelial cell](/details-cell/CL0000706)` (CSI: 5.28) and `[secretory cell](/details-cell/CL0000151)` (CSI: 4.78). This pattern suggests that its role extends to maintaining organelle integrity in cells responsible for secretion and transport, which are also energy-intensive processes. The data collectively positions [SPATA18](/details-gene/132671) as a key homeostatic factor in specialized epithelial cells that are under constant metabolic demand. ## Pathways and Molecular Function [SPATA18](/details-gene/132671) is fundamentally involved in mitochondrial homeostasis through its central role in mitophagy. Its gene ontology annotations highlight its function in `[Mitochondrial protein catabolic process](/details-go/GO:0035694)` and `[Mitophagy by internal vacuole formation](/details-go/GO:0035695)`. Mechanistically, the SPATA18 protein localizes to the `[mitochondrial outer membrane](/details-go/GO:0005741)` where it can bind to cardiolipin ([Link](https://www.ebi.ac.uk/QuickGO/term/GO:1901612)). Following cellular stress signals, such as DNA damage, its expression is induced by p53. The SPATA18 protein then facilitates the accumulation of lysosomal proteins within the mitochondria, effectively creating a lysosome-like organelle to degrade unhealthy mitochondrial components from within ([Link](https://doi.org/10.1371/journal.pone.0016054), [Link](https://doi.org/10.1371/journal.pone.0030767)). This connection to the `[Dna damage response](/details-go/GO:0006974)` pathway via p53/p63 regulation ([Link](https://doi.org/10.1128/mcb.01072-10)) underscores its function as a guardian of cellular integrity. By eliminating damaged mitochondria, which can be a major source of reactive oxygen species (ROS), [SPATA18](/details-gene/132671) helps prevent further cellular damage and maintain genomic stability. Its annotated role in `[Molecular condensate scaffold activity](/details-go/GO:0140693)` may relate to its ability to organize the protein machinery required for this unique intramitochondrial degradation process. ## Research Directions The specific expression pattern of [SPATA18](/details-gene/132671) in high-energy-demand epithelial cells, coupled with its role as a p53-inducible mitophagy regulator, opens several avenues for future investigation. **Testable Hypotheses:** 1. **Impaired Mucociliary Clearance:** Given its high significance in ciliated cells, loss-of-function of [SPATA18](/details-gene/132671) may lead to the accumulation of dysfunctional mitochondria, resulting in reduced ciliary beat frequency and impaired mucociliary clearance. This could predispose individuals to respiratory conditions characterized by ciliary defects (ciliopathies). 2. **Tumor Suppression and Chemoresistance:** As a p53 target that maintains mitochondrial health, [SPATA18](/details-gene/132671) likely functions as a tumor suppressor in epithelial tissues by preventing the accumulation of oncogenic mutations driven by mitochondrial ROS. Its downregulation or inactivation in cancers could contribute to tumor progression and promote resistance to chemotherapies that act by inducing mitochondrial damage. **Proposed Experimental Approach:** To test the hypothesis that [SPATA18](/details-gene/132671) is essential for ciliary function, an experiment could be designed using an *in vitro* model of the human airway. * **Model:** Primary human bronchial epithelial cells would be cultured at an air-liquid interface (ALI) to induce differentiation into a mature, ciliated epithelium. * **Methodology:** [SPATA18](/details-gene/132671) would be knocked out using CRISPR-Cas9 in these cells prior to differentiation. Control cells would be treated with a non-targeting gRNA. * **Analysis:** After full differentiation, the cultures would be assessed for several endpoints: ciliary beat frequency using high-speed video microscopy, mitochondrial health via staining with TMRE (tetramethylrhodamine, ethyl ester) and imaging, and overall mucociliary transport efficiency by tracking the movement of fluorescent microspheres placed on the epithelial surface. It would be expected that [SPATA18](/details-gene/132671)-knockout cultures would exhibit reduced ciliary beating, increased mitochondrial depolarization, and slower particle transport compared to controls. **Therapeutic Potential:** The role of [SPATA18](/details-gene/132671) as a p53-regulated guardian of mitochondrial integrity suggests it may be a tumor suppressor. In cancers where [SPATA18](/details-gene/132671) expression is lost or silenced, cells may become more tolerant of mitochondrial dysfunction, which can support cancer cell survival and proliferation. Therefore, restoring its function represents a potential therapeutic strategy. This would involve **activation** rather than inhibition. Small molecule compounds designed to specifically upregulate [SPATA18](/details-gene/132671) expression or enhance its mitophagic activity could be explored as a way to re-sensitize epithelial-derived tumors to conventional therapies that induce mitochondrial stress, such as certain chemotherapies or radiation.

Genular Protein ID: 2719038772

Symbol: MIEAP_HUMAN

Name: Mitochondria-eating protein

UniProtKB Accession Codes:

Q8TC71 B4E2R0 E5RLK1 Q8IY48 Q8N7D7

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 8 Ensembl 2 ExpressionAtlas 1 GO 8 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 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 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: 21264221

Title: Possible existence of lysosome-like organella within mitochondria and its role in mitochondrial quality control.

PubMed ID: 21264221

DOI: 10.1371/journal.pone.0016054

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 21300779

Title: SPATA18, a spermatogenesis-associated gene, is a novel transcriptional target of p53 and p63.

PubMed ID: 21300779

DOI: 10.1128/mcb.01072-10

PubMed ID: 21264228

Title: Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria.

PubMed ID: 21264228

DOI: 10.1371/journal.pone.0016060

PubMed ID: 22292033

Title: BNIP3 and NIX mediate Mieap-induced accumulation of lysosomal proteins within mitochondria.

PubMed ID: 22292033

DOI: 10.1371/journal.pone.0030767

Sequence Information:

  • Length: 538
  • Mass: 61109
  • Checksum: 365754F577F8ED7F
  • Sequence:
    • MAENLKRLVS NETLRTLQEK LDFWLKEYNT NTCDQNLNHC LELIEQVAKV QGQLFGILTA 
AAQEGGRNDG VETIKSRLLP WLEASFTAAS LGKSVDSKVP SLQDTFDRER HKDPSPRDRD 
MQQLDSNLNS TRSQCNQVQD DLVETEKNLE ESKNRSAISL LAAEEEINQL KKQLKSLQAQ 
EDARHRNTDQ RSSENRRSEP WSLEERKREQ WNSLKQNADQ QDTEAMSDYK KQLRNLKEEI 
AVLSAEKSAL QGRSSRSRSP SPAPRSRSCS RSRSASPSTA VKVRRPSPNR SKLSNVARKA 
ALLSRFSDSY SQARLDAQCL LRRCIDKAET VQRIIYIATV EAFHVAKMAF RHFKIHVRKS 
LTPSYVGSND FENAVLDYVI CHLDLYDSQS SVNDVIRAMN VNPKISFPPV VDFCLLSDFI 
QEICCIAFAM QALEPPLDIA YGADGEVFND CKYRRSYDSD FTAPLVLYHV WPALMENDCV 
IMKGEAVTRR GAFWNSVRSV SRCRSRSLSP ICPRSQIGLN TMSRSRSPSP IRCGLPRF