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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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IER2
immediate early response 2
Chromosome 19 · 19p13.13
NCBI Gene: 9592Ensembl: ENSG00000160888.9HGNC: HGNC:28871UniProt: Q9BTL4
24PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmcytoplasmpositive regulation of transcription by RNA polymerase IIcell motilityvenous thromboembolismneurodegenerative diseasemelanomaosteoarthritis, knee
✦AI Summary

IER2 (immediate early response 2) is a nuclear transcription factor that functions as a key regulator of cell motility and tumor progression across multiple cancer types. Mechanistically, IER2 translocates from the cytoplasm to the nucleus upon cellular stress, where it transcriptionally activates target genes including integrin β1 (ITGB1), which subsequently activates FAK-Src-paxillin signaling to promote cell adhesion and migration 1. In colorectal cancer, IER2 expression positively correlates with metastatic potential and poor patient survival 2. Beyond its canonical roles, IER2 functions in distinct cellular contexts: in melanoma, sustained IER2 expression induces senescence via p53/MAPK/AKT pathways, causing senescent cells to secrete osteopontin that paradoxically stimulates non-senescent cell invasion 3. In chordoma, hypoxia-mediated upregulation of IER2 in cancer-associated fibroblasts promotes tumor progression through paracrine GMFG-ITGB1 signaling 4. Additionally, IER2 functions in developmental processes as an FGF signaling effector; zebrafish and Xenopus studies demonstrate IER2 requirement for ciliogenesis and left-right asymmetry establishment during embryogenesis 5 6. Clinically, elevated IER2 expression serves as a prognostic indicator of aggressive phenotype and poor survival across colorectal adenocarcinoma, hepatocellular carcinoma, melanoma, and bladder cancer.

Sources cited
1
IER2 promotes tumor cell motility and metastasis; correlates with poor survival in colorectal cancer patients
PMID: 22120713
2
IER2 regulates HCC cell adhesion and motility by transcriptionally promoting ITGB1 and activating FAK-Src-paxillin signaling
PMID: 27840969
3
IER2-induced senescence drives melanoma invasion through osteopontin secretion via p53/MAPK/AKT pathway
PMID: 34611309
4
Hypoxia upregulates IER2 in cancer-associated fibroblasts to promote chordoma progression via GMFG/ITGB1 axis
PMID: 39207055
5
IER2 mediates FGF signaling in ciliogenesis and left-right asymmetry establishment in zebrafish embryos
PMID: 19164561
6
XIer2 is required for convergent extension movements during Xenopus development
PMID: 22252488
Disease Associationsⓘ20
venous thromboembolismOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.13Weak
melanomaOpen Targets
0.08Suggestive
osteoarthritis, kneeOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
exfoliation syndromeOpen Targets
0.04Suggestive
skin neoplasmOpen Targets
0.04Suggestive
brain aneurysmOpen Targets
0.03Suggestive
Abnormality of the cardiovascular systemOpen Targets
0.03Suggestive
chordomaOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
asthmaOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
glaucomaOpen Targets
0.01Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
ovarian cancerOpen Targets
0.01Suggestive
Melnick-Needles syndromeOpen Targets
0.01Suggestive
Miyoshi myopathyOpen Targets
0.01Suggestive
glioblastoma multiformeOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOSProtein interaction96%JUNBProtein interaction91%ATF3Protein interaction75%DUSP1Protein interaction75%EGR1Protein interaction75%FOSBProtein interaction75%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
69%
Liver
47%
Ovary
47%
Brain
12%
Heart
10%
Gene Interaction Network
Click a node to explore
IER2FOSJUNBATF3DUSP1EGR1FOSB
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BTL4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.68Intermediate
Observed/Expected LoF0.00 [0.00–0.95]
RankingsWhere IER2 stands among ~20K protein-coding genes
  • #13,206of 20,598
    Most Researched24
  • #8,974of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedIER2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1.
PMID: 39207055
Adv Sci (Weinh) · 2024
1.00
2
The immediate early gene Ier2 promotes tumor cell motility and metastasis, and predicts poor survival of colorectal cancer patients.
PMID: 22120713
Oncogene · 2012
0.90
3
IER2-induced senescence drives melanoma invasion through osteopontin.
PMID: 34611309
Oncogene · 2021
0.80
4
Immediate early response protein 2 regulates hepatocellular carcinoma cell adhesion and motility via integrin β1-mediated signaling pathway.
PMID: 27840969
Oncol Rep · 2017
0.70
5
FGF-dependent left-right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1.
PMID: 19164561
Proc Natl Acad Sci U S A · 2009
0.60