PDIA4 Gene

HGNC Family	Protein disulfide isomerases (PDI)
Name	protein disulfide isomerase family A, member 4
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 ER-signal sequence, three catalytically active thioredoxin (TRX) domains, two TRX-like domains and a C-terminal ER-retention sequence. This protein, when bound to cyclophilin B, enhances the rate of immunoglobulin G intermolecular disulfide bonding and antibody assembly. [provided by RefSeq, Dec 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein disulfide isomerase A4 (PDIA4) is a multifunctional endoplasmic reticulum (ER) chaperone that plays pivotal roles in protein folding and processing. Its aberrant overexpression has been reported in a wide range of malignancies, including esophageal squamous cell carcinoma, non‐small cell lung cancer, lung adenocarcinoma, gastric cancer, cervical cancer, prostate cancer, ovarian cancer, triple‐negative breast cancer, and even glioblastoma, where elevated PDIA4 levels correlate with chemoresistance, tumor progression, and poor patient outcomes. In these contexts, PDIA4 contributes to oncogenesis not only as a potential biomarker but also by promoting cell survival through inhibition of apoptotic pathways and supporting resistance to various therapies, while even circular RNAs derived from its pre‐mRNA have been implicated in sustaining oncogenic signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to supporting tumor progression, PDIA4 directly regulates cell death pathways. Its overexpression has been shown to interfere with the activation and degradation of procaspases—thereby suppressing classical apoptotic signaling—while also conferring resistance to ferroptosis, a regulated form of cell death. These anti‐cell death mechanisms render cancer cells more resilient under therapeutic pressures."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in oncogenesis, PDIA4 is a key mediator of the ER stress response and metabolic regulation. In placental tissues, for instance, cytokines such as interleukin‐11 upregulate PDIA4 and contribute to ER stress that has been linked to obstetric complications. In metabolic disorders, altered PDIA4 expression is associated with components of the metabolic syndrome, including obesity and insulin resistance, while pharmacological agents like metformin appear to modulate PDIA4 expression and alleviate associated inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, PDIA4 contributes to the maintenance of vascular homeostasis by sustaining autophagic flux in endothelial cells and preventing endothelial-to-mesenchymal transition through modulation of TGFβ signaling. Its role extends to host–pathogen interactions as well; during certain viral infections, ER stress-induced upregulation of PDIA4 facilitates viral RNA synthesis and release, highlighting its potential as a target for antiviral therapeutics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Harsh Pawar, Manoj Kumar Kashyap, Nandini A Sahasrabuddhe, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2013.193"}], "href": "https://doi.org/10.1038/cdd.2013.193"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24464223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24464223"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "T-F Kuo, T-Y Chen, S-T Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2017.156"}], "href": "https://doi.org/10.1038/onc.2017.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28534513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28534513"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yue Shen, Nasha Zhang, Jie Chai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircPDIA4 Induces Gastric Cancer Progression by Promoting ERK1/2 Activation and Enhancing Biogenesis of Oncogenic circRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-22-1923"}], "href": "https://doi.org/10.1158/0008-5472.CAN-22-1923"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36562654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36562654"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Feng Xing, Zhijiao Song, Zhongping Cheng "}, {"type": "b", "children": [{"type": "t", "text": "High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2022.8399"}], "href": "https://doi.org/10.3892/or.2022.8399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36082822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36082822"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Subo Qian, Shun Zhang, Yu Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-023-01758-6"}], "href": "https://doi.org/10.1186/s13058-023-01758-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38167446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38167446"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hyeon Ji Kim, DO-Yeon Kim "}, {"type": "b", "children": [{"type": "t", "text": "Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.17260"}], "href": "https://doi.org/10.21873/anticanres.17260"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39348977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39348977"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yao Chanjiao, Chen Chunyan, Qiu Xiaoxin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-378a-3p contributes to ovarian cancer progression through downregulating PDIA4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immun Inflamm Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iid3.350"}], "href": "https://doi.org/10.1002/iid3.350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33159506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33159506"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chanjiao Yao, Lingjuan Zeng, Qin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast J (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2023/3970444"}], "href": "https://doi.org/10.1155/2023/3970444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37720188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37720188"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zewei Tu, Chong Wang, Qing Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-023-02640-1"}], "href": "https://doi.org/10.1186/s13046-023-02640-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36997943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36997943"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Lichun Kang, Dekun Wang, Tianyu Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-05719-x"}], "href": "https://doi.org/10.1038/s41419-023-05719-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36906674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36906674"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "A L Winship, K Sorby, J Correia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-11 up-regulates endoplasmic reticulum stress induced target, PDIA4 in human first trimester placenta and in vivo in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Placenta (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.placenta.2017.04.007"}], "href": "https://doi.org/10.1016/j.placenta.2017.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28487027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28487027"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Chu-Yen Chien, Yi-Jen Hung, Yi-Shing Shieh, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2022.1053882"}], "href": "https://doi.org/10.3389/fendo.2022.1053882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36619574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36619574"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sheng-Chiang Su, Chu-Yen Chien, Ying-Chen Chen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms25073913"}], "href": "https://doi.org/10.3390/ijms25073913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38612722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38612722"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Mengwei Xu, Huan Xu, Weiwei Wan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Viruses (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/v15122343"}], "href": "https://doi.org/10.3390/v15122343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38140584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38140584"}]}]}]}
Synonyms	ERP70, ERP-72, ERP72
Proteins	PDIA4_HUMAN
NCBI Gene ID	9601
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDIA4 has 11,798 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 122 datasets.

Click the + buttons to view associations for PDIA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDIA4 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDIA4 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 PDIA4 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 PDIA4 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 PDIA4 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 PDIA4 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 PDIA4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PDIA4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PDIA4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PDIA4 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 PDIA4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDIA4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PDIA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PDIA4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDIA4 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 PDIA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDIA4 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 PDIA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PDIA4 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDIA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PDIA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDIA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PDIA4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PDIA4 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 PDIA4 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 PDIA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PDIA4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDIA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDIA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDIA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDIA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PDIA4 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 PDIA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PDIA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PDIA4 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 PDIA4 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 PDIA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDIA4 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 PDIA4 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 PDIA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PDIA4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.