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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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EMX1
empty spiracles homeobox 1
Chromosome 2 · 2p13.2
NCBI Gene: 2016Ensembl: ENSG00000135638.15HGNC: HGNC:3340UniProt: Q04741
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleolusprotein bindingsequence-specific double-stranded DNA bindingnucleusschizophrenianeurodegenerative diseasemuscular dystrophymirror movements 1
✦AI Summary

EMX1 is a homeobox transcription factor that functions primarily in nervous system development and organogenesis. During neural development, EMX1 cooperates with EMX2 to establish boundaries between brain regions and works with OTX1/2 to specify cell fates in the developing central nervous system 1. In neural differentiation contexts, EMX1 coordinates with proneural factors like NGN2 to redirect their genomic binding and promote specification of glutamatergic neurons while silencing alternative neurotransmitter programs 2. Beyond the brain, EMX1 regulates nephron distal segment development in zebrafish by acting downstream of retinoic acid signaling and controlling expression of irx3b, irx1a, and sim1a 3. In disease contexts, EMX1 exhibits context-dependent roles. In hepatocellular carcinoma, DNA hypermethylation activates EMX1 full-length isoform (EMX1-FL), which promotes tumor metastasis by binding the EGFR promoter and activating EGFR-ERK signaling 4. Conversely, in sarcomas, EMX1 acts as a tumor suppressor by negatively regulating WNT pathway signaling and repressing cancer stem cell gene expression 5. These opposing roles highlight the importance of tissue and context-specific EMX1 function in disease pathogenesis.

Sources cited
1
EMX1 cooperates with proneural factor NGN2 to redirect genomic binding and promote glutamatergic neuron specification
PMID: 38446849
2
EMX1 and EMX2 are vertebrate homeobox genes related to Drosophila ems gene expressed in developing head
PMID: 7896134
3
DNA hypermethylation-activated EMX1-FL promotes hepatocellular carcinoma metastasis via EGFR-ERK signaling axis
PMID: 38007497
4
EMX1 regulates nephron distal segment development in zebrafish by controlling irx3b, irx1a, and sim1a expression downstream of retinoic acid
PMID: 30575756
5
EMX1 acts as tumor suppressor in sarcomas by negatively regulating WNT pathway and cancer stem cell genes
PMID: 34364391
6
Emx1-Cre mouse strains show recombination activity in kidney nephron epithelial cells
PMID: 39479517
7
Emx1-Cre mice used to study CIRBP-mediated neuroprotection in hypoxia-induced ferroptosis
PMID: 38388728
Disease Associationsⓘ20
schizophreniaOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
muscular dystrophyOpen Targets
0.11Weak
mirror movements 1Open Targets
0.10Suggestive
schizencephalyOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
sarcomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
complex cortical dysplasia with other brain malformations 1Open Targets
0.05Suggestive
Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutationOpen Targets
0.05Suggestive
complex cortical dysplasia with other brain malformations 6Open Targets
0.04Suggestive
Genetic central nervous system malformationOpen Targets
0.04Suggestive
Microcephaly - polymicrogyria - corpus callosum agenesisOpen Targets
0.04Suggestive
microcephaly-polymicrogyria-corpus callosum agenesis syndromeOpen Targets
0.04Suggestive
complex cortical dysplasia with other brain malformations 7Open Targets
0.04Suggestive
Polymicrogyria due to TUBB2B mutationOpen Targets
0.04Suggestive
polymicrogyria with optic nerve hypoplasiaOpen Targets
0.04Suggestive
central nervous system cancerOpen Targets
0.04Suggestive
vaginal disorderOpen Targets
0.03Suggestive
primary ovarian insufficiencyOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NOTOShared pathway100%GSX1Shared pathway100%VAX1Shared pathway100%EMX2Shared pathway100%TBR1Protein interaction82%FOXG1Protein interaction80%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
5%
Liver
4%
Ovary
1%
Lung
1%
Heart
0%
Gene Interaction Network
Click a node to explore
EMX1NOTOGSX1VAX1EMX2TBR1FOXG1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q04741
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.32LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.48–1.32]
RankingsWhere EMX1 stands among ~20K protein-coding genes
  • #13,410of 20,598
    Most Researched23
  • #13,902of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedEMX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1.
PMID: 38446849
Proc Natl Acad Sci U S A · 2024
1.00
2
Vertebrate homeobox genes.
PMID: 7896134
Genetica · 1994
0.90
3
DNA methylation-activated full-length EMX1 facilitates metastasis through EMX1-EGFR-ERK axis in hepatocellular carcinoma.
PMID: 38007497
Cell Death Dis · 2023
0.80
4
Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing.
PMID: 38773978
Theranostics · 2024
0.70
5
Homeogene emx1 is required for nephron distal segment development in zebrafish.
PMID: 30575756
Sci Rep · 2018
0.60