IER2

Chr 19

immediate early response 2

Also known as: CHX1, ETR101

NCBI Gene: 9592ENSG00000160888UniProt: Q9BTL4

Predicted to enable DNA binding activity. Involved in cell motility and positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. Implicated in colorectal cancer and hepatocellular carcinoma. Biomarker of childhood acute myeloid leukemia; colorectal adenocarcinoma; hepatocellular carcinoma; and melanoma. [provided by Alliance of Genome Resources, Jul 2025]

68
ClinVar variants
23
Pathogenic / LP
0.77
pLI score
0
Active trials
Clinical Summary— IER2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 44 VUS of 68 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.
0.62LOEUF
pLI 0.768
Z-score 2.04
OE 0.00 (0.00–0.62)
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.
-0.53Z-score
OE missense 1.14 (0.99–1.31)
134 obs / 117.8 exp
Tolerant

Tolerant to missense variation

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 (0.00–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.14 (0.99–1.31)
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.1.45
0≤1.21.6
LoF obs/exp: 0 / 4.8Missense obs/exp: 134 / 117.8Syn Z: -2.63

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS44
Benign1
20
Pathogenic
3
Likely Pathogenic
44
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
3
0
3
VUS
0
36
8
0
44
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total03731068

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

View in ClinVar →

Protein Context — Lollipop Plot

IER2 · 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
Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1.
Zhang TL et al.·Adv Sci (Weinh)
2024
Immediate early response protein 2 regulates hepatocellular carcinoma cell adhesion and motility via integrin β1-mediated signaling pathway.
Xu Z et al.·Oncol Rep
2017
Immediate early response protein 2 promotes the migration and invasion of hepatocellular carcinoma cells via regulating the activity of Rho GTPases.
Xu X et al.·Neoplasma
2020
Neutrophil Transcriptional Deregulation by the Periodontal Pathogen Fusobacterium nucleatum in Gastric Cancer: A Bioinformatic Study.
Zhou T et al.·Dis Markers
2022
Influence of surgical manipulation on prostate gene expression: implications for molecular correlates of treatment effects and disease prognosis.
Lin DW et al.·J Clin Oncol
2006
Bayesian Network Inference Modeling Identifies TRIB1 as a Novel Regulator of Cell-Cycle Progression and Survival in Cancer Cells.
Gendelman R et al.·Cancer Res
2017Functional
Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.
Ferguson JF et al.·J Nutr Biochem
2016
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