The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The literature retrieved here is consistent with the requested target: human TXNDC16 (thioredoxin domain-containing protein 16), also referred to as ERp90, and described as an ER-luminal glycoprotein with ER-targeting/retention features. This matches the UniProt-provided identity and the stated thioredoxin-like domain architecture. (harz2014secretionandimmunogenicity pages 1-2, oliveira2025endoplasmicreticulumredoxome pages 4-5)
Proteins with thioredoxin-like domains in the endoplasmic reticulum (ER) often participate in oxidative protein folding, quality control, and ER-associated degradation (ERAD). Many have catalytic CXXC active-site motifs to mediate thiol–disulfide exchange; however, some members are non-catalytic, functioning as scaffolds/adaptors within folding/ERAD complexes rather than directly catalyzing disulfide chemistry. TXNDC16 is repeatedly placed in this ER oxidoreductase/quality-control context. (oliveira2025endoplasmicreticulumredoxome pages 4-5, patel2020oxidoreductasesinglycoprotein pages 7-9)
Secretory-pathway proteins are typically targeted to the ER by an N-terminal signal peptide, enabling cotranslational ER translocation via SRP/Sec61 and signal-peptidase cleavage. ER luminal resident proteins commonly use C-terminal KDEL-like motifs for retrieval from the Golgi back to the ER, though these signals can be context-dependent or functionally masked. TXNDC16 includes a predicted signal peptide and a KDEL-variant (DKEL), but its retention can be incomplete. (harz2014secretionandimmunogenicity pages 2-3, harz2014secretionandimmunogenicity pages 6-6)
TXNDC16 was described as having a molecular mass of ~93 kDa (reference sequence cited in the primary paper) and being broadly expressed across normal and many cancer tissues. (harz2014secretionandimmunogenicity pages 1-2)
A key point for functional annotation is that TXNDC16/ERp90 contains multiple thioredoxin-like domains but is annotated in an authoritative ER folding/ERAD review as having inactive/non-canonical Trx-like motifs (e.g., CX8C, CX9C, CX6C rather than canonical catalytic CXXC). This is presented as evidence that ERp90 is non-catalytic (i.e., not a classical thiol–disulfide oxidoreductase enzyme), supporting a role as a structural/complex component in ER quality control rather than a substrate-specific oxidoreductase. (patel2020oxidoreductasesinglycoprotein pages 5-7, patel2020oxidoreductasesinglycoprotein pages 7-9)
Implication for “primary function” request: based on the retrieved sources, TXNDC16 is best described as a PDI/thioredoxin-domain-containing ER quality-control factor without a clearly defined catalytic reaction or specific substrate list; its functional evidence is stronger at the pathway/complex level (ERAD association) than at the substrate-specific enzymology level. (patel2020oxidoreductasesinglycoprotein pages 7-9, patel2020oxidoreductasesinglycoprotein pages 5-7)
Harz et al. (2014, J Immunol, published online Aug 13, 2014; issue Sep 2014; https://doi.org/10.4049/jimmunol.1303098) performed confocal microscopy in human cells expressing TXNDC16-HA and reported colocalization with PDI, an ER-luminal marker, supporting ER localization. Deleting the first 27 amino acids (the predicted signal peptide) shifted localization from ER-associated to cytosolic, showing the signal peptide is required for ER targeting. (harz2014secretionandimmunogenicity pages 3-4)
Visual evidence for ER localization and domain schematic is present in the paper’s figures. (harz2014secretionandimmunogenicity media 3c06b519, harz2014secretionandimmunogenicity media d160178d)
Despite harboring a KDEL-like motif (DKEL), Harz et al. report that TXNDC16 can be secreted into supernatants from multiple human cell lines, and they interpret this as being due to a masked/nonfunctional ER retrieval motif (i.e., incomplete ER retention). They further report detection of TXNDC16 protein in serum, bound in circulating immune complexes, and discuss uncertainty regarding whether secretion is classical ER/Golgi-dependent or unconventional. They did not confirm a previously suggested exosomal secretion mechanism in HEK293 cells (CD63-marked fraction). (harz2014secretionandimmunogenicity pages 1-2, harz2014secretionandimmunogenicity pages 6-6, harz2014secretionandimmunogenicity pages 8-8)
In a widely cited review on oxidoreductases in glycoprotein folding and ERAD (Patel et al., 2020, Cells, Sep 2020; https://doi.org/10.3390/cells9092138), TXNDC16 (ERp90) is specifically placed in the ERAD (retrotranslocation) category and described as non-catalytic. The review reports interactions/associations with the ERAD lectin OS-9 and adaptor SEL1L, and positions ERp90 in assemblies alongside other ERAD redox/processing factors (e.g., ERdj5; ERFAD noted as NADPH-dependent reductase). This supports a model where TXNDC16 acts as a component of ERAD machinery—likely in recognition/scaffolding or organization of ERAD complexes—rather than directly performing thiol–disulfide catalysis. (patel2020oxidoreductasesinglycoprotein pages 5-7, patel2020oxidoreductasesinglycoprotein pages 7-9)
A more recent review of the ER redoxome includes TXNDC16 among PDI/thioredoxin-domain-containing proteins (alias ERp90), reinforcing its placement within ER proteostasis/redox networks, while not adding TXNDC16-specific mechanistic detail in the excerpt retrieved. (oliveira2025endoplasmicreticulumredoxome pages 4-5)
Korte & Mathios (2024, International Journal of Molecular Sciences, Apr 2024; https://doi.org/10.3390/ijms25084195) review liquid biopsy approaches for meningioma and summarize prior TXNDC16 work as a meningioma-associated antigen. They cite evidence that a panel of five TXNDC16 immunogenic epitopes (derived from mapping 163 overlapping peptides) could discriminate meningioma from healthy sera with ~90% sensitivity and ~83.7% specificity, framing this as a proof-of-concept serology/autoantibody liquid biopsy approach. They also provide expert cautions that tumor-associated antigen (TAA) autoantibodies can lack specificity across cancers or occur in autoimmunity/healthy individuals, implying that TXNDC16 would likely perform best as part of multi-antigen panels and within well-validated clinical workflows. (korte2024innovationinnoninvasive pages 7-9)
Within the retrieved 2023–2024 corpus, TXNDC16 appears mainly in review/omics contexts rather than in detailed mechanistic papers focused on TXNDC16. A 2024 PNAS study in mouse testis proteomics (in the context of multi-gene knockout in the WFDC cluster) notes TXNDC16 upregulation among proteins associated with protein degradation/quality control, which is directionally consistent with an ER quality-control role but is not TXNDC16-specific mechanistic proof in human cells. (kent2024largescalecrisprcas9deletions pages 8-9)
The most concrete translational “implementation pathway” is serum-based detection of anti-TXNDC16 autoantibodies using peptide arrays or reduced epitope panels. This is supported by primary serology results (Harz et al. 2014) and positioned within the broader liquid biopsy landscape in a 2024 review, but remains a proof-of-concept rather than an approved clinical test. (harz2014secretionandimmunogenicity pages 6-7, korte2024innovationinnoninvasive pages 7-9)
In cell biology and proteostasis research, TXNDC16/ERp90 is used as a named component of the ERAD retrotranslocation network (OS-9/SEL1L-associated), which can guide experimental design (e.g., ERAD complex mapping, perturbation studies of ER proteostasis). This is a “real-world” research application as part of ERAD conceptual/interaction maps. (patel2020oxidoreductasesinglycoprotein pages 7-9)
Harz et al. (2014, J Immunol; https://doi.org/10.4049/jimmunol.1303098) report that while no single TXNDC16 epitope was universally recognized, a five-epitope subset chosen from a 163-peptide overlapping array discriminated meningioma vs controls with ~87.2% accuracy, ~90% sensitivity, and ~83.7% specificity; using all peptides yielded substantially worse performance (~53.8% accuracy, ~24.2% specificity, ~77.3% sensitivity). These values are restated in the 2024 review as evidence supporting TXNDC16’s biomarker potential. (harz2014secretionandimmunogenicity pages 6-7, korte2024innovationinnoninvasive pages 7-9)
Open Targets returns low association scores for TXNDC16 with several diseases (including meningioma and Alzheimer disease), but with zero underlying evidence rows in the retrieved output. These associations therefore should not be treated as strong evidence of causality or clinical utility without supporting primary genetics/functional studies. (OpenTargets Search: -TXNDC16)
| Aspect | Finding | Best supporting citations |
|---|---|---|
| Identity/synonyms | TXNDC16 is the human gene matching UniProt Q9P2K2; reported synonyms include ERp90 and KIAA1344. Harz 2014 identifies TXNDC16 as a meningioma-associated antigen and notes it had previously been characterized as an ER-luminal glycoprotein. Harz 2014, J Immunol, published Sep 2014, URL: https://doi.org/10.4049/jimmunol.1303098 | (harz2014secretionandimmunogenicity pages 1-2) |
| Domains/motifs | TXNDC16/ERp90 is a thioredoxin domain-containing, PDI-family-like protein. Review evidence places it in the ER oxidoreductase network but notes its Trx-like motifs are non-canonical/inactive rather than classical catalytic CXXC motifs: Trxl1-CX8C, Trxl2-CX9C, Trxl3-CX6C, Trxl4/5 inactive. It also has a predicted N-terminal 27 aa signal peptide and a C-terminal DKEL KDEL-like motif. Patel 2020, Cells, Sep 2020, URL: https://doi.org/10.3390/cells9092138 | (patel2020oxidoreductasesinglycoprotein pages 5-7, harz2014secretionandimmunogenicity pages 2-3, harz2014secretionandimmunogenicity media 3c06b519) |
| Subcellular localization | Experimental data support predominant ER luminal/ER-associated localization. TXNDC16-HA colocalizes with PDI by confocal microscopy, and deleting the signal peptide shifts localization from ER-associated to cytosolic, showing signal-peptide-dependent ER targeting. Harz 2014, J Immunol, Sep 2014, URL: https://doi.org/10.4049/jimmunol.1303098 | (harz2014secretionandimmunogenicity pages 3-4, harz2014secretionandimmunogenicity media 3c06b519) |
| Secretion/extracellular presence | Despite ER-targeting features, TXNDC16 is also reported in cell-culture supernatants and serum/circulating immune complexes. Harz 2014 concluded secretion likely reflects a masked/nonfunctional ER retrieval motif; the authors could not confirm prior exosomal secretion in HEK293 cells. Korte 2024 highlights this as a basis for liquid-biopsy interest. Korte 2024, Int J Mol Sci, Apr 2024, URL: https://doi.org/10.3390/ijms25084195 | (harz2014secretionandimmunogenicity pages 1-2, harz2014secretionandimmunogenicity pages 6-6, harz2014secretionandimmunogenicity pages 8-8, korte2024innovationinnoninvasive pages 7-9, harz2014secretionandimmunogenicity pages 6-7) |
| Proposed molecular function | Current evidence supports TXNDC16 as an ER quality-control/thioredoxin-like scaffold or chaperone-associated factor, not a well-established classical oxidoreductase enzyme. Because its Trx-like domains lack canonical catalytic motifs, the strongest inference is a role in ER protein folding/quality control and ERAD-associated processes, rather than a defined substrate-specific disulfide isomerase reaction. Patel 2020, Cells, Sep 2020, URL: https://doi.org/10.3390/cells9092138 | (patel2020oxidoreductasesinglycoprotein pages 5-7, oliveira2025endoplasmicreticulumredoxome pages 4-5) |
| Interactions/complexes | TXNDC16/ERp90 is specifically linked to ERAD retrotranslocation machinery, with reported interactions involving OS-9 and SEL1L in review summaries of ER glycoprotein quality control. This places TXNDC16 in pathways handling misfolded glycoproteins in the ER. Patel 2020, Cells, Sep 2020, URL: https://doi.org/10.3390/cells9092138 | (patel2020oxidoreductasesinglycoprotein pages 5-7) |
| Disease/biomarker evidence | The clearest disease-relevant evidence is in meningioma serology. TXNDC16 was identified as a meningioma-associated antigen with autoantibody reactivity; Korte 2024 reviews it as a proof-of-concept liquid biopsy biomarker based on serum autoantibodies/peptide arrays. Open Targets currently lists only very weak association scores with zero underlying evidence rows for diseases including meningioma, Alzheimer disease, chronic kidney disease, eye disease, and tinnitus, so these database associations should be treated cautiously. Open Targets query context available in this session. | (korte2024innovationinnoninvasive pages 7-9, harz2014secretionandimmunogenicity pages 6-7, OpenTargets Search: -TXNDC16) |
| Key statistics | Harz 2014 reports TXNDC16 has a ~93 kDa predicted molecular mass and that a 5-epitope panel derived from 163 overlapping peptides discriminated meningioma vs controls with 87.2% accuracy, 90% sensitivity, and 83.7% specificity; using all peptides performed much worse (53.8% accuracy, 24.2% specificity, 77.3% sensitivity). Korte 2024 reiterates the approximate 90% sensitivity / 83.7% specificity result as support for non-invasive biomarker development. Harz 2014, J Immunol, Sep 2014, URL: https://doi.org/10.4049/jimmunol.1303098; Korte 2024, Int J Mol Sci, Apr 2024, URL: https://doi.org/10.3390/ijms25084195 | (harz2014secretionandimmunogenicity pages 1-2, korte2024innovationinnoninvasive pages 7-9, harz2014secretionandimmunogenicity pages 6-7) |
Table: This table summarizes the strongest available functional annotation evidence for human TXNDC16/ERp90, including identity verification, ER localization, inferred molecular role, ERAD associations, and current biomarker evidence. It is useful for distinguishing well-supported findings from weaker database-level disease associations.
References
(harz2014secretionandimmunogenicity pages 1-2): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(oliveira2025endoplasmicreticulumredoxome pages 4-5): Percillia V. S. Oliveira, Tiphany C. De Bessa, and Francisco R. M. Laurindo. Endoplasmic reticulum redoxome: protein folding and beyond. Biochemistry, 65(1):1-30, Dec 2025. URL: https://doi.org/10.1021/acs.biochem.5c00527, doi:10.1021/acs.biochem.5c00527. This article has 7 citations and is from a peer-reviewed journal.
(patel2020oxidoreductasesinglycoprotein pages 7-9): Chaitanya Patel, Haddas Saad, Marina Shenkman, and Gerardo Z. Lederkremer. Oxidoreductases in glycoprotein glycosylation, folding, and erad. Sep 2020. URL: https://doi.org/10.3390/cells9092138, doi:10.3390/cells9092138. This article has 33 citations.
(harz2014secretionandimmunogenicity pages 2-3): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(harz2014secretionandimmunogenicity pages 6-6): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(patel2020oxidoreductasesinglycoprotein pages 5-7): Chaitanya Patel, Haddas Saad, Marina Shenkman, and Gerardo Z. Lederkremer. Oxidoreductases in glycoprotein glycosylation, folding, and erad. Sep 2020. URL: https://doi.org/10.3390/cells9092138, doi:10.3390/cells9092138. This article has 33 citations.
(harz2014secretionandimmunogenicity pages 3-4): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(harz2014secretionandimmunogenicity media 3c06b519): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(harz2014secretionandimmunogenicity media d160178d): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(harz2014secretionandimmunogenicity pages 8-8): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(korte2024innovationinnoninvasive pages 7-9): Brianna Korte and Dimitrios Mathios. Innovation in non-invasive diagnosis and disease monitoring for meningiomas. International Journal of Molecular Sciences, 25:4195, Apr 2024. URL: https://doi.org/10.3390/ijms25084195, doi:10.3390/ijms25084195. This article has 11 citations.
(kent2024largescalecrisprcas9deletions pages 8-9): Katarzyna Kent, Kaori Nozawa, Rachel Parkes, Laura Dean, Frey Daniel, Mei Leng, Antrix Jain, Anna Malovannaya, Martin M. Matzuk, and Thomas X. Garcia. Large-scale crispr/cas9 deletions within the wfdc gene cluster uncover gene functionality and critical roles in mammalian reproduction. Proceedings of the National Academy of Sciences of the United States of America, Dec 2024. URL: https://doi.org/10.1073/pnas.2413195121, doi:10.1073/pnas.2413195121. This article has 10 citations and is from a highest quality peer-reviewed journal.
(harz2014secretionandimmunogenicity pages 6-7): Christian Harz, Nicole Ludwig, Sven Lang, Tamara V. Werner, Valentina Galata, Christina Backes, Katja Schmitt, Ruth Nickels, Elmar Krause, Martin Jung, Jens Rettig, Andreas Keller, Michael Menger, Richard Zimmermann, and Eckart Meese. Secretion and immunogenicity of the meningioma-associated antigen txndc16. The Journal of Immunology, 193:3146-3154, Sep 2014. URL: https://doi.org/10.4049/jimmunol.1303098, doi:10.4049/jimmunol.1303098. This article has 10 citations.
(OpenTargets Search: -TXNDC16): Open Targets Query (-TXNDC16, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.