IER3
protein-codingimmediate early response 3
Gene summary
This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.3 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 IER3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003897.4. 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 | 0 | |||||
| missense | 19 | 3 | 22 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 20 | 3 | 0 | 23 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003888.2 | 2 | MANE Select | |
| Ensembl | ENSP00000259874.5 | 2 | MANE Select | |
| Ensembl | ENSP00000365557.2 | 1 | Standard | |
| Ensembl | ENSP00000587936.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apoptosis-related network due to altered Notch3 in ovarian cancer
- Signal Transduction
- PIP3 activates AKT signaling
- PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
- Negative regulation of the PI3K/AKT network
Biological Process
- apoptotic process
- anatomical structure morphogenesis
- regulation of phosphatidylinositol 3-kinase signaling
- negative regulation of apoptotic process
- regulation of response to DNA damage stimulus
Molecular Function
- protein binding
Cellular Component
- nucleus
- cytosol
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000259874
- Coding exons
- 2
- Length
- 1356
- Individuals with no LoFs
- 125194
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125195
- p
- 0.00000399
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.23 | 55 | 87.5 | 0.629 | 0.00000388 | 970 |
| Missense (PolyPhen) | 9 | 26.644 | 0.33779 | 310 | ||
| Synonymous | 1.00 | 31 | 39.0 | 0.795 | 0.00000181 | 359 |
| Loss of Function | 1.66 | 0 | 3.19 | 0.00 | 1.43e-7 | 32 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A- PPP2R5C holoenzyme. Acts also as an ERK downstream effector mediating survival. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:16456541, ECO:0000269|PubMed:22565310}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.983
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |