IER3

Chr 6

immediate early response 3

Also known as: DIF-2, DIF2, GLY96, IEX-1, IEX-1L, IEX1, PRG1

NCBI Gene: 8870ENSG00000137331UniProt: P46695

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]

32
ClinVar variants
5
Pathogenic / LP
0.63
pLI score
0
Active trials
Clinical Summary— IER3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 24 VUS of 32 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.631
Z-score 1.66
OE 0.00 (0.00–0.93)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.23Z-score
OE missense 0.63 (0.51–0.79)
55 obs / 87.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.51–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 0 / 3.2Missense obs/exp: 55 / 87.5Syn Z: 1.00

ClinVar Variant Classifications

32 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS24
Likely Benign3
4
Pathogenic
1
Likely Pathogenic
24
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
19
5
0
24
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total02210032

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IER3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury.
Tang R et al.·Chin Med J (Engl)
2023Cohort
ANGPTL4 mediated mesothelial-mesenchymal transition in pulmonary fibrosis: a potential therapeutic target.
Xia Y et al.·J Transl Med
2024
Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor.
Carrillo-García J et al.·Eur J Cancer
2024
Expression of IER3 in primary hepatocarcinoma: correlation with clinicopathological parameters.
Liu Z et al.·Asian Pac J Cancer Prev
2015
Identification and validation of apoptosis-related genes in acute myocardial infarction based on integrated bioinformatics methods.
Zhu H et al.·PeerJ
2024
IER3 (IEX-1) dysregulation serves as a potential prognostic factor in acute myeloid leukemia patients.
Ke S et al.·Int J Lab Hematol
2022Cohort
Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites.
Luo Y et al.·Sci Rep
2025
Correlation study of NF-κB, IER3, and Recurrence of Ovarian Endometrioid Cysts.
Fan X et al.·Reprod Sci
2025
IER3 promotes non-small cell lung cancer malignancy by suppressing ferroptosis via the AKT/GSK3β/NRF2 pathway.
Chen Y et al.·Free Radic Biol Med
2026
The molecular pathogenesis of myelodysplastic syndromes.
Davids MS et al.·Cancer Biol Ther
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools