Details for: TXNDC8

Gene ID: 255220

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: TXNDC8

Ensembl ID: ENSG00000204193

Description: thioredoxin domain containing 8

Cell Significance Landscape

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 3.05
    rCSI 6.19%
    PRS 99.19

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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  • 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 [TXNDC8](/details-gene/255220), or Thioredoxin Domain Containing 8, is a protein-coding gene located on chromosome 9. It functions primarily as a protein-disulfide reductase, an activity essential for correct protein folding and cellular redox homeostasis. Gene Ontology annotations link [TXNDC8](/details-gene/255220) to fundamental biological processes such as [cell differentiation](/details-cell/GO:0030154) and, more specifically, [spermatogenesis](/details-cell/GO:0007283). Its protein product is localized to several cellular compartments, including the [cytoplasm](/details-cell/GO:0005737), [Golgi apparatus](/details-cell/GO:0005794), and [acrosomal vesicle](/details-cell/GO:0001669), which is consistent with its role in processing proteins for sperm development. Expression data indicates that **Overall**, [TXNDC8](/details-gene/255220) is a significant marker for [ependymal cell](/details-cell/CL0000065), suggesting a specialized role in the central nervous system in addition to its well-documented function in male germ cells. ## Cellular Roles and Expression Landscape The expression profile of [TXNDC8](/details-gene/255220) points towards highly specialized cellular functions. **Overall**, the gene shows its most significant expression in [ependymal cell](/details-cell/CL0000065) (CSI: 3.05), which are the ciliated epithelial-like cells lining the ventricles of the brain and the central canal of the spinal cord. This specific expression suggests a potential role for [TXNDC8](/details-gene/255220) in the maintenance of the ventricular system or the regulation of cerebrospinal fluid composition, possibly through its protein-folding activity. In addition to this finding, published research provides strong evidence for a critical role of a related thioredoxin in male reproductive biology. One study identified a spermatocyte/spermatid-specific thioredoxin, localized to the [Golgi apparatus](/details-cell/GO:0005794), as a key component of spermatogenesis and a specific marker for its aberrant forms [Link](https://doi.org/10.1074/jbc.m404192200). This aligns with its annotated function in [spermatogenesis](/details-cell/GO:0007283) and localization to the [acrosomal vesicle](/details-cell/GO:0001669), a structure critical for fertilization. The presence of [TXNDC8](/details-gene/255220) in [extracellular exosome](/details-cell/GO:0070062) also suggests it may participate in intercellular signaling in these specialized environments. ## Pathways and Molecular Function The primary molecular function of [TXNDC8](/details-gene/255220) is its [protein-disulfide reductase activity](/details-cell/GO:0015035). This enzymatic function is crucial for catalyzing the reduction of disulfide bonds in proteins, a key step in protein folding, repair, and redox signaling. Its strong association with the [Golgi apparatus](/details-cell/GO:0005794) is consistent with this role, as this organelle is a major site of post-translational modification and protein maturation. This reductase activity is the mechanistic basis for its involvement in complex biological processes. In [spermatogenesis](/details-cell/GO:0007283), [TXNDC8](/details-gene/255220) likely ensures the correct folding and assembly of proteins required for sperm head formation and the biogenesis of the [acrosomal vesicle](/details-cell/GO:0001669), an organelle essential for penetrating the egg during fertilization. Dysfunction in this pathway could lead to improperly formed sperm, consistent with its characterization as a marker for aberrant spermatogenesis [Link](https://doi.org/10.1074/jbc.m404192200). Its broader role in [cell differentiation](/details-cell/GO:0030154) may be attributed to the general requirement for robust protein folding machinery as cells adopt specialized forms and functions, as seen in both male germ cells and [ependymal cell](/details-cell/CL0000065). ## Research Directions The dual-context expression of [TXNDC8](/details-gene/255220) in both the reproductive system and the central nervous system presents compelling avenues for future research. While its role in spermatogenesis is supported by literature, its high significance in ependymal cells is a novel finding that warrants further investigation. **Proposed Hypotheses:** 1. The high and specific expression of [TXNDC8](/details-gene/255220) in [ependymal cell](/details-cell/CL0000065) is essential for maintaining the integrity of the ventricular-brain barrier and regulating the proteome of the cerebrospinal fluid through its protein-disulfide reductase activity. 2. Given that it is a marker for aberrant spermatogenesis [Link](https://doi.org/10.1074/jbc.m404192200), [TXNDC8](/details-gene/255220) could serve as a diagnostic biomarker for specific subtypes of male infertility, with its levels in seminal exosomes correlating with defects in acrosome formation and sperm motility. **Experimental Approach:** To test the first hypothesis regarding the function of [TXNDC8](/details-gene/255220) in the central nervous system, a targeted experimental approach is necessary. A conditional knockout mouse model could be generated using a *Foxj1-Cre* driver, which specifically targets ciliated cells, including [ependymal cell](/details-cell/CL0000065). Analysis of these mice would focus on detecting neurological phenotypes such as hydrocephalus, defects in cerebrospinal fluid flow, and breakdown of the ependymal cell layer. Proteomic analysis of the cerebrospinal fluid from knockout and wild-type mice could then directly assess whether loss of [TXNDC8](/details-gene/255220) leads to an accumulation of misfolded or aggregated proteins. **Therapeutic Potential:** [TXNDC8](/details-gene/255220) is more promising as a diagnostic biomarker than as a direct therapeutic target. Its specific expression during spermatogenesis suggests that its levels, perhaps measured in seminal plasma or testicular biopsies, could be developed into a specific assay for diagnosing forms of male infertility related to protein folding defects in the Golgi. Direct therapeutic targeting is challenging; as an enzyme involved in the fundamental process of protein folding, inhibitors would likely carry a high risk of off-target toxicity. However, should its dysfunction be linked to specific neurological or reproductive disorders, strategies aimed at modulating its activity or compensating for its loss, rather than simple inhibition, might be considered in the future.

Genular Protein ID: 2992587512

Symbol: TXND8_HUMAN

Name: Thioredoxin domain-containing protein 8

UniProtKB Accession Codes:

Q6A555 A1L4I2 A6NDK7 Q5T934

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 6 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 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 3 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 15181017

Title: Spermatocyte/spermatid-specific thioredoxin-3, a novel Golgi apparatus-associated thioredoxin, is a specific marker of aberrant spermatogenesis.

PubMed ID: 15181017

DOI: 10.1074/jbc.m404192200

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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

Sequence Information:

  • Length: 127
  • Mass: 14575
  • Checksum: 94BBF008A82CBD8F
  • Sequence:
    • MVQIIKDTNE FKTFLTAAGH KLAVVQFSSK RCGPCKRMFP VFHAMSVKYQ NVFFANVDVN 
NSPELAETCH IKTIPTFQMF KKSQKVTLFS RIKRIICCYR SGFMSNLIFE FCGADAKKLE 
AKTQELM

Genular Protein ID: 2257076876

Symbol: A9Z1W9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A9Z1W9

Database IDs:

ARBA 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 EMBL 3 Ensembl 2 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 2 Proteomes 2 RefSeq 1 SAM 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 108
  • Mass: 12301
  • Checksum: 12D4EDB203661987
  • Sequence:
    • MVQIIKDTNE FKTFLTAAGH KLAVVQFSSK RCGPCKRMFP VFHELAETCH IKTIPTFQMF 
KKSQKGSISR PTPTSELHPH QKWTLDSSQA NPSQTRANFR TLLKQLGK

Genular Protein ID: 3990331650

Symbol: B7ZME0_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7ZME0

Database IDs:

ARBA 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 EMBL 3 Ensembl 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 2 Proteomes 2 RefSeq 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

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: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 95
  • Mass: 10912
  • Checksum: 0744291957B31578
  • Sequence:
    • MVQIIKDTNE FKTFLTAAGH KLAVVQFSSK RCGPCKRMFP VFHELAETCH IKTIPTFQMF 
KKSQKVTLFS RIKRIICCYR SGFMSNLCLA DDGNE