ERN2 (Endoplasmic Reticulum to Nucleus Signaling 2)
Gene encoding IRE1β, a key sensor of the unfolded protein response in the endoplasmic reticulum
Gene Information Card
| Symbol | ERN2 |
|---|---|
| Full Name | Endoplasmic Reticulum to Nucleus Signaling 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p12.2 |
| NCBI Gene ID | 10595 ncbi.nlm.nih.gov/gene/10595 |
| Ensembl ID | ENSG00000134398 |
| UniProt ID | Q76MJ5 |
| OMIM ID | 604574 |
| HGNC ID | 3447 |
| Aliases | IRE1β, IRE1-BETA, hIRE1b |
Description
ERN2 encodes inositol-requiring enzyme 1 beta (IRE1β), a transmembrane protein in the endoplasmic reticulum (ER) that acts as a sensor of unfolded proteins. It possesses both serine/threonine kinase and endoribonuclease domains, mediating the unfolded protein response (UPR) by splicing XBP1 mRNA. IRE1β is predominantly expressed in intestinal and lung epithelial cells, playing a specialized role in mucosal homeostasis and ER stress adaptation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease | Dysregulated UPR in intestinal epithelium; ERN2 variants may impair XBP1 splicing, leading to ER stress and inflammation | PMID: 18454146 |
| Colorectal Cancer | Altered ERN2 expression linked to tumor progression; loss of IRE1β function may promote survival of stressed cancer cells | COSMIC: ERN2 mutations in colorectal tumors |
| Respiratory Epithelial Stress | ERN2 deficiency in lung epithelium increases susceptibility to ER stress-induced apoptosis | PMID: 21884936 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 12.5 | Medium |
| Colon | 8.3 | Medium |
| Lung | 6.1 | Low |
| Stomach | 4.2 | Low |
| Esophagus | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colorectal adenocarcinoma) | 15.2 | Intestinal epithelial model |
| HT-29 (colorectal adenocarcinoma) | 10.7 | Colonic epithelial line |
| A549 (lung carcinoma) | 5.4 | Lung epithelial line |
| HCT 116 (colorectal carcinoma) | 7.8 | Colorectal cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1672C>T (p.Arg558Cys) | Missense | <0.01% | Potential loss of kinase activity; reported in COSMIC |
| c.2143G>A (p.Gly715Ser) | Missense | <0.01% | Located in RNase domain; may impair XBP1 splicing |
| c.1234_1235insA (p.Thr412Asnfs*5) | Frameshift | <0.01% | Truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in kinase or RNase domains reduce or abolish IRE1β activity, impairing UPR signaling.
Gain of Function (GOF)
Not documented in ERN2; no known activating mutations.
Dominant Negative (DN)
Not reported; ERN2 functions as a homodimer, but dominant-negative effects have not been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR) - IRE1α/β branch
• XBP1(S) transcription factor pathway
• ER stress-induced apoptosis
Protein Summary
IRE1β (UniProt Q76MJ5) is a 923-amino acid transmembrane protein with an N-terminal luminal domain that senses ER stress, a cytosolic kinase domain, and a C-terminal endoribonuclease domain. Upon ER stress, IRE1β dimerizes and autophosphorylates, activating its RNase to splice XBP1 mRNA, producing a potent transcription factor that upregulates chaperones and ERAD components. Unlike the ubiquitously expressed IRE1α, IRE1β is restricted to epithelial tissues, particularly intestine and lung, where it fine-tunes the UPR to maintain barrier function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERN2 Knockout HEK293 Cell Line | EDJ-KQ7103 | Human | 10595 | Details Get a Quote |
| ERN2 Knockout HeLa Cell Line | EDJ-KQ55441 | Human | 10595 | Details Get a Quote |
| ERN2 Knockout A-549 Cell Line | EDJ-KQ63921 | Human | 10595 | Details Get a Quote |
| ERN2 Knockout HCT 116 Cell Line | EDJ-KQ72379 | Human | 10595 | Details Get a Quote |
