PDIA5 Gene

HGNC Family	Protein disulfide isomerases (PDI)
Name	protein disulfide isomerase family A, member 5
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, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [provided by RefSeq, Dec 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein disulfide isomerase A5 (PDIA5) plays a pivotal role in maintaining endoplasmic reticulum (ER) homeostasis by catalyzing the rearrangement of disulfide bonds. Under conditions of ER stress, PDIA5 mediates the disulfide bond rearrangement of the membrane‐anchored transcription factor ATF6α. This re‐modelling facilitates ATF6α export from the ER via COPII vesicles and initiates the transcription of its target genes—a mechanism that, when activated, contributes to chemoresistance in cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of tumor progression, PDIA5 is frequently overexpressed in aggressive gliomas and other human cancers. Elevated PDIA5 expression correlates with enhanced immune cell infiltration and activation of immune‐related pathways, often accompanied by increased markers of macrophage exhaustion. Such alterations in the tumor microenvironment not only predict poorer clinical outcomes but also suggest that PDIA5 is involved in modulating immune checkpoint activity and inflammatory responses, rendering it a promising candidate for targeted immunotherapeutic approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in glioblastoma multiforme (GBM), PDIA5 promotes malignant behaviors by enhancing cellular proliferation, clone formation, and invasion. Mechanistic studies have delineated a regulatory axis whereby RUNX1 transcriptionally activates PDIA5, which in turn modulates downstream effectors such as CCAR1 to drive GBM progression. This regulatory pathway not only reinforces PDIA5’s central role in tumor biology but also emphasizes its potential as a therapeutic target to mitigate aggressive cancer phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arisa Higa, Said Taouji, Stéphanie Lhomond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endoplasmic reticulum stress-activated transcription factor ATF6α requires the disulfide isomerase PDIA5 to modulate chemoresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01484-13"}], "href": "https://doi.org/10.1128/MCB.01484-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24636989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24636989"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hao Zhang, Jialin He, Ziyu Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2021.628966"}], "href": "https://doi.org/10.3389/fimmu.2021.628966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33664747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33664747"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yu Chen, Jialin He, Rui Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pan-Cancer Analysis of the Immunological Role of PDIA5: A Potential Target for Immunotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2022.881722"}], "href": "https://doi.org/10.3389/fimmu.2022.881722"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36003400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36003400"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qiankun Ji, Zewei Tu, Junzhe Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RUNX1-PDIA5 Axis Promotes Malignant Progression of Glioblastoma by Regulating CCAR1 Protein Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.92595"}], "href": "https://doi.org/10.7150/ijbs.92595"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39247813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39247813"}]}]}]}
Synonyms	PDIR
Proteins	PDIA5_HUMAN
NCBI Gene ID	10954
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDIA5 has 6,209 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for PDIA5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDIA5 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 PDIA5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PDIA5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDIA5 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 PDIA5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PDIA5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDIA5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDIA5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDIA5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDIA5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PDIA5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PDIA5 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 PDIA5 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 PDIA5 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 PDIA5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDIA5 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 PDIA5 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 PDIA5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PDIA5 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 PDIA5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PDIA5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PDIA5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.