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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EGR4
early growth response 4
Chromosome 2 · 2p13.2
NCBI Gene: 1961Ensembl: ENSG00000135625.8HGNC: HGNC:3241UniProt: A0A0C4DG96
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific DNA bindingsequence-specific double-stranded DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificpositive regulation of transcription by RNA polymerase IIneurodegenerative diseaseskull disorderSplenomegalygeneralized dystonia
✦AI Summary

EGR4 (early growth response 4) is a transcriptional regulator that plays critical roles in reproductive biology, cancer progression, and cellular differentiation. As a transcription factor containing Cys2His2 zinc finger domains, EGR4 directly binds to specific DNA sequences to activate target gene expression 1. In male fertility, EGR4 regulates spermatogonial stem cell function and germ cell maturation, with alterations in its expression associated with impaired spermatogenesis 2 3. The protein shows high conservation across species, sharing 80-87% identity between bovine, mouse, rat, and human orthologs 1. In cancer contexts, EGR4 promotes tumor progression through multiple mechanisms. In gastric cancer, it transcriptionally upregulates GDF15, driving metastasis via ErbB3/ErbB1 heterodimerization and activating PI3K/AKT and MAPK/ERK pathways 4. In colorectal cancer, EGR4 promotes cell proliferation by upregulating TNFα and activating NF-κB signaling 5. EGR4 also demonstrates tissue-specific expression patterns, being highly expressed in ovaries and central nervous system tissues 6. Additionally, EGR4 shows protective functions in diabetic retinopathy through the AdipoR1/AMPK pathway 7, highlighting its diverse physiological roles beyond reproduction and cancer.

Sources cited
1
EGR4 is a transcription factor with Cys2His2 zinc finger domains and shares 80-87% identity across species
PMID: 12648095
2
EGR4 regulates spermatogonial stem cell function with alterations associated with impaired spermatogenesis
PMID: 34622232
3
EGR4 variations are associated with male infertility and germ cell maturation
PMID: 28464846
4
EGR4 transcriptionally upregulates GDF15 in gastric cancer, promoting metastasis via ErbB3/ErbB1 and PI3K/AKT pathways
PMID: 41203604
5
EGR4 promotes colorectal cancer cell proliferation by upregulating TNFα and activating NF-κB signaling
PMID: 38459370
6
EGR4 shows tissue-specific expression in ovaries and central nervous system
PMID: 23719176
7
EGR4 demonstrates protective functions in diabetic retinopathy through AdipoR1/AMPK pathway
PMID: 38166990
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.32Weak
skull disorderOpen Targets
0.30Weak
SplenomegalyOpen Targets
0.24Weak
generalized dystoniaOpen Targets
0.15Weak
azoospermiaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
small cell lung carcinomaOpen Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
spinocerebellar ataxia type 32Open Targets
0.06Suggestive
Isolated follicle stimulating hormone deficiencyOpen Targets
0.06Suggestive
isochromosomy YpOpen Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.06Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
spermatogenic failure 71Open Targets
0.06Suggestive
spermatogenic failure 63Open Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TMEM250Shared pathway100%CDCA7LShared pathway100%TSPAN31Shared pathway100%NAB2Protein interaction99%NAB1Protein interaction98%EGR2Protein interaction76%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
61%
Heart
2%
Liver
0%
Ovary
0%
Lung
0%
Gene Interaction Network
Click a node to explore
EGR4TMEM250CDCA7LTSPAN31NAB2NAB1EGR2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q05215
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.56LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.10 [0.78–1.56]
RankingsWhere EGR4 stands among ~20K protein-coding genes
  • #13,894of 20,598
    Most Researched21
  • #15,494of 17,882
    Most Constrained (LOEUF)1.56
Genes detectedEGR4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell RNA-seq unravels alterations of the human spermatogonial stem cell compartment in patients with impaired spermatogenesis.
PMID: 34622232
Cell Rep Med · 2021
1.00
2
EGR4 transcriptionally upregulates GDF15 to promote gastric cancer metastasis.
PMID: 41203604
Cell Death Dis · 2025
0.90
3
Cloning and characterization of the bovine EGR4 gene and evaluation as candidate gene for bovine spinal dysmyelination.
PMID: 12648095
Anim Genet · 2003
0.80
4
The novel porcine gene early growth response 4 (Egr4) is differentially expressed in the ovaries of Erhualian and Pietrain pigs.
PMID: 23719176
Reprod Fertil Dev · 2014
0.70
5
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma.
PMID: 36915208
Genome Med · 2023
0.60