ERN2
protein-codingendoplasmic reticulum to nucleus signaling 2
Gene summary
Enables several functions, including ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apoptotic chromosome condensation; negative regulation of DNA-templated transcription; and rRNA catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ERN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033266.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 8 | 1 | 13 | ||
| missense | 53 | 1 | 1 | 55 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 59 | 9 | 2 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_150296.4 | 22 | MANE Select | |
| Ensembl | ENSP00000256797.5 | 22 | MANE Select | |
| RefSeq | NP_001295149.2 | 21 | Standard | |
| Ensembl | ENSP00000413812.2 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mRNA processing
- protein phosphorylation
- cell cycle arrest
- activation of JUN kinase activity
- rRNA catabolic process
Molecular Function
- magnesium ion binding
- endonuclease activity
- endoribonuclease activity
- ribonuclease activity
- protein kinase activity
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- IRE1-TRAF2-ASK1 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256797
- Coding exons
- 22
- Length
- 23175
- Individuals with no LoFs
- 125457
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 290
- Defined
- 125748
- p
- 0.00116
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.295 | 587 | 567 | 1.03 | 0.0000332 | 6177 |
| Missense (PolyPhen) | 218 | 229.23 | 0.95103 | 2461 | ||
| Synonymous | 0.0807 | 242 | 244 | 0.993 | 0.0000144 | 2098 |
| Loss of Function | 1.38 | 42 | 52.8 | 0.795 | 0.00000305 | 526 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.00093 | 0.00093 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0014 | 0.0014 | notable |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.0026 | 0.0026 | notable |
| Other | 0.0021 | 0.0021 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. Pro-apoptotic. Appears to play no role in the unfolded-protein response, unlike closely related proteins. {ECO:0000269|PubMed:11175748}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.989
- RVIS EVS
- -1.7
- RVIS percentile EVS
- 2.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.140
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |