ERO1A Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the ERO1A gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | ERO1A |
|---|---|
| Full Name | Endoplasmic Reticulum Oxidoreductase 1 Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 14q22.1 |
| NCBI Gene ID | 30001 ncbi.nlm.nih.gov/gene/30001 |
| Ensembl ID | ENSG00000197930 |
| UniProt ID | Q96HE7 |
| OMIM ID | 615435 |
| HGNC ID | 13265 |
| Aliases | ERO1L, ERO1-L, ERO1-L alpha, Endoplasmic oxidoreductin-1-L, Oxidoreductin-1-L |
Description
The ERO1A gene encodes the endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) protein, a key enzyme in the endoplasmic reticulum (ER) that catalyzes the formation of disulfide bonds in nascent proteins. ERO1α transfers electrons from protein disulfide isomerase (PDI) to molecular oxygen, generating hydrogen peroxide as a byproduct. This process is essential for proper protein folding and secretion. ERO1A expression is induced by ER stress and hypoxia, and it plays a role in various physiological and pathological processes, including cancer progression, angiogenesis, and metabolic regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | ERO1A overexpression promotes tumor growth, metastasis, and chemoresistance by enhancing oxidative protein folding, reducing ER stress-induced apoptosis, and modulating the tumor microenvironment. | High expression observed in breast, lung, colorectal, and hepatocellular carcinomas; associated with poor prognosis (multiple studies, e.g., PMID: 25944712, 27630125). |
| Hypoxia-related pathologies | ERO1A is upregulated under hypoxic conditions via HIF-1α, contributing to cellular adaptation and survival in ischemic tissues. | Demonstrated in cell lines and animal models (e.g., PMID: 19491311). |
| Neurodegenerative diseases | Altered ERO1A expression may contribute to ER stress-induced neuronal death in conditions like Alzheimer's and Parkinson's disease. | Preliminary evidence from post-mortem brain studies (e.g., PMID: 23395347). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Esophagus | 17.1 | Medium |
| Liver | 15.2 | Medium |
| Kidney | 12.8 | Medium |
| Pancreas | 11.5 | Medium |
| Lung | 9.8 | Low |
| Breast | 8.4 | Low |
| Brain | 5.2 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 22.3 | High expression; consistent with liver tissue data. |
| A549 (lung cancer) | 15.7 | Moderate expression; may reflect hypoxia-induced upregulation. |
| MCF7 (breast cancer) | 12.1 | Moderate expression; associated with estrogen receptor status. |
| K562 (leukemia) | 6.5 | Low expression; not a major site of ERO1A activity. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Cys) | Missense | Rare (MAF <0.01%) | Potential loss of function; affects redox-active site; not well characterized. |
| c.454G>A (p.Gly152Ser) | Missense | Rare | Unknown functional impact; no clinical association reported. |
| c.1021A>G (p.Ile341Val) | Missense | Rare | Likely benign; no disease association. |
| c.1285C>T (p.Arg429Trp) | Missense | Rare | Potential impact on protein stability; not validated. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ERO1A are rare and not well documented. Complete knockout in mice is embryonic lethal, indicating essentiality. Partial loss may impair oxidative protein folding and lead to ER stress.
Gain of Function (GOF)
Gain-of-function mutations are not reported. Overexpression (not mutation) is the primary mechanism in cancer, leading to enhanced disulfide bond formation and tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been described for ERO1A.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • protein disulfide isomerase activity |
| • endoplasmic reticulum lumen | • response to endoplasmic reticulum stress |
| • protein folding | • cell redox homeostasis |
| • oxidation-reduction process | • chaperone binding |
Pathways
• Endoplasmic reticulum stress response (UPR)
• Protein processing in endoplasmic reticulum
• HIF-1 signaling pathway
• Metabolic pathways
Protein Summary
ERO1α is a 468-amino acid protein localized to the endoplasmic reticulum. It contains a flavin adenine dinucleotide (FAD) binding domain and a thioredoxin-like domain. The enzyme oxidizes PDI, which in turn oxidizes substrate proteins, facilitating disulfide bond formation. ERO1α uses molecular oxygen as the final electron acceptor, producing hydrogen peroxide. Its activity is regulated by redox-dependent conformational changes and by post-translational modifications. ERO1α is overexpressed in many cancers and contributes to tumor aggressiveness.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERO1A Knockout HEK293 Cell Line | EDJ-KQ9130 | Human | 30001 | Details Get a Quote |
| ERO1A Knockout HeLa Cell Line | EDJ-KQ34416 | Human | 30001 | Details Get a Quote |
| ERO1A Knockout A-549 Cell Line | EDJ-KQ35666 | Human | 30001 | Details Get a Quote |
| ERO1A Knockout HCT 116 Cell Line | EDJ-KQ35667 | Human | 30001 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
