TXNDC5 Gene

HGNC Family	Protein disulfide isomerases (PDI)
Name	thioredoxin domain containing 5 (endoplasmic reticulum)
Description	This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTXNDC5, also known as ERp46 or Endo‐PDI, is an endoplasmic reticulum–resident protein disulfide isomerase that catalyzes disulfide bond formation, reduction, and isomerization during oxidative protein folding. Its structure, defined by multiple thioredoxin domains and unusually long interdomain loops, underlies its ability to bind diverse peptide substrates and to interact directly with key ER proteins—such as EDEM3, where redox‐dependent disulfide exchange couples its enzymatic activity with mannose trimming, and with the adiponectin receptor AdipoR1 to modulate receptor signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several pathological contexts TXNDC5 is markedly upregulated and contributes to disease progression. In tumorigenesis, elevated TXNDC5 expression is detected early in colorectal adenomas and cancers and is similarly increased in gastric adenocarcinomas, non‐small cell lung carcinomas, and a variety of other solid tumors where it promotes cellular proliferation, survival, and migration, thereby acting as a tumor–enhancing gene. In addition, TXNDC5 has been implicated in fibrotic diseases; by interacting with and stabilizing TGFβ receptor 1, it amplifies TGFβ1 signaling to drive fibrogenesis in both pulmonary and cardiac tissues. Moreover, in castration–resistant prostate cancer TXNDC5 upregulation increases androgen receptor stability and transcriptional activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTXNDC5 also modulates cellular responses to endoplasmic reticulum stress and inflammatory signals. In rheumatoid arthritis synovial fibroblasts, it promotes pro–inflammatory cytokine production by interacting with heat shock cognate 70 and altering NF–κB signaling, while in conditions such as vitiligo its chaperone activity is thought to mitigate oxidative ER stress. These functions point to TXNDC5 as a stress–responsive survival factor whose dysregulation may contribute not only to cancer and fibrosis but also to immune–mediated and pigmentary disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shangyu Yu, Shinji Ito, Ikuo Wada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.003129"}], "href": "https://doi.org/10.1074/jbc.RA118.003129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29784879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29784879"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hayley K Charlton, Julie Webster, Sarah Kruger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2010.01.029"}], "href": "https://doi.org/10.1016/j.bbrc.2010.01.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20074551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20074551"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Fengbo Tan, Hong Zhu, Xiao He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of TXNDC5 in tumorigenesis of colorectal cancer cells: In vivo and in vitro evidence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2018.3664"}], "href": "https://doi.org/10.3892/ijmm.2018.3664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29749460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29749460"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yinghong Wang, Yu Ma, Bingjian Lü, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of mimecan and thioredoxin domain-containing protein 5 in colorectal adenoma and cancer: a proteomic study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3181/0701-RM-8"}], "href": "https://doi.org/10.3181/0701-RM-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17895523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17895523"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lin Zhang, Yanhong Hou, Nan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The influence of TXNDC5 gene on gastric cancer cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-010-0807-x"}], "href": "https://doi.org/10.1007/s00432-010-0807-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20157732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20157732"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Emma E Vincent, Douglas J E Elder, Lois Phillips, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the TXNDC5 protein in non-small cell lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21617212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21617212"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiaotian Chang, Bing Xu, Lin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigating a pathogenic role for TXNDC5 in tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2013.2123"}], "href": "https://doi.org/10.3892/ijo.2013.2123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24100949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24100949"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "L Wang, G Song, X Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of TXNDC5 in castration-resistant prostate cancer-involvement of androgen receptor signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.401"}], "href": "https://doi.org/10.1038/onc.2014.401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25500540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25500540"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ying-Chun Shih, Chao-Ling Chen, Yan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.117.312130"}], "href": "https://doi.org/10.1161/CIRCRESAHA.117.312130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29535165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29535165"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tzu-Han Lee, Chih-Fan Yeh, Ying-Tung Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-18047-x"}], "href": "https://doi.org/10.1038/s41467-020-18047-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32848143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32848143"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaotian Chang, Yan Zhao, Xinfeng Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Res Ther (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/ar3429"}], "href": "https://doi.org/10.1186/ar3429"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21801346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21801346"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "K-H Jeong, M-K Shin, Y-K Uhm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Dermatol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2133.2009.09574.x"}], "href": "https://doi.org/10.1111/j.1365-2133.2009.09574.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19906073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19906073"}]}]}]}
Synonyms	UNQ364, HCC2, ENDOPDI, PDIA15, STRF8, ERP46
Proteins	TXND5_HUMAN
NCBI Gene ID	81567
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TXNDC5 has 6,743 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for TXNDC5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TXNDC5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by TXNDC5 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TXNDC5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of TXNDC5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of TXNDC5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TXNDC5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of TXNDC5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TXNDC5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TXNDC5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TXNDC5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TXNDC5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TXNDC5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TXNDC5 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TXNDC5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TXNDC5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of TXNDC5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TXNDC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TXNDC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing TXNDC5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TXNDC5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with TXNDC5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of TXNDC5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TXNDC5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TXNDC5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TXNDC5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TXNDC5 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TXNDC5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TXNDC5 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TXNDC5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TXNDC5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with TXNDC5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TXNDC5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TXNDC5 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TXNDC5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TXNDC5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing TXNDC5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TXNDC5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TXNDC5 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TXNDC5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TXNDC5 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing TXNDC5 from the GeneSigDB Published Gene Signatures dataset.