PDIA4 Gene (Protein Disulfide Isomerase Family A Member 4)
Endoplasmic Reticulum Chaperone and Oxidoreductase Involved in Protein Folding and Cancer
Gene Information Card
| Symbol | PDIA4 |
|---|---|
| Full Name | Protein Disulfide Isomerase Family A Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q35 |
| NCBI Gene ID | 9601 ncbi.nlm.nih.gov/gene/9601 |
| Ensembl ID | ENSG00000105974 |
| UniProt ID | P13667 |
| OMIM ID | 176810 |
| HGNC ID | 9020 |
| Aliases | ERP72, ERp-72, ERp72 |
Description
PDIA4 (Protein Disulfide Isomerase Family A Member 4) encodes an endoplasmic reticulum (ER) resident protein that belongs to the protein disulfide isomerase (PDI) family. It functions as a molecular chaperone and oxidoreductase, catalyzing the formation, reduction, and isomerization of disulfide bonds during protein folding. PDIA4 is upregulated under ER stress and is involved in the unfolded protein response (UPR). It has been implicated in cancer progression, neurodegenerative diseases, and immune modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | PDIA4 overexpression promotes tumor cell survival by alleviating ER stress and enhancing protein folding capacity. | COSMIC; PMID: 31570853 |
| Alzheimer's disease | PDIA4 is upregulated in response to amyloid-beta-induced ER stress, contributing to neuroprotection or dysfunction. | PMID: 25664836 |
| Diabetes | PDIA4 modulates insulin biosynthesis and beta-cell survival under ER stress conditions. | PMID: 23395179 |
| Rheumatoid arthritis | PDIA4 is elevated in synovial tissue and may contribute to inflammatory cytokine production. | PMID: 27343003 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 48.2 | High |
| Liver | 35.1 | High |
| Kidney | 28.7 | High |
| Salivary gland | 24.5 | Medium |
| Thyroid | 22.0 | Medium |
| Brain | 12.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 62.5 | Embryonic kidney cells; high expression |
| HepG2 | 55.3 | Hepatocellular carcinoma; high expression |
| MCF7 | 48.1 | Breast cancer; moderate expression |
| A549 | 40.2 | Lung adenocarcinoma; moderate expression |
| K562 | 18.7 | Chronic myeloid leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123G>A (p.Gly375Arg) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.1670C>T (p.Pro557Leu) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.1966_1968del (p.Lys656del) | In-frame deletion | <0.01% | Unknown; rare variant in population databases |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in PDIA4.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PDIA4.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in PDIA4.
View complete mutation data：
Gene Ontology (GO)
| • protein disulfide isomerase activity (GO:0003756) | • endoplasmic reticulum (GO:0005783) |
| • protein folding (GO:0006457) | • response to endoplasmic reticulum stress (GO:0034976) |
| • cell redox homeostasis (GO:0045454) | • unfolded protein binding (GO:0051082) |
Pathways
• Endoplasmic reticulum protein processing (KEGG: hsa04141)
• Unfolded protein response (Reactome: R-HSA-381119)
• Protein folding (Reactome: R-HSA-391251)
Protein Summary
PDIA4 (ERP72) is a 72 kDa endoplasmic reticulum-resident protein containing four thioredoxin-like domains (a, b, b', a') with two active site CGHC motifs. It catalyzes disulfide bond formation and isomerization, and acts as a chaperone to prevent protein aggregation. PDIA4 is induced by ER stress and plays a protective role in cells. Its overexpression is observed in various cancers and is associated with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDIA4 Knockout HEK293 Cell Line | EDJ-KQ933 | Human | 9601 | Details Get a Quote |
| PDIA4 Knockout A-549 Cell Line | EDJ-KQ18272 | Human | 9601 | Details Get a Quote |
| PDIA4 Knockout HCT 116 Cell Line | EDJ-KQ19911 | Human | 9601 | Details Get a Quote |
| PDIA4 Knockout HeLa Cell Line | EDJ-KQ19912 | Human | 9601 | Details Get a Quote |
