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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ETV5
ETS variant transcription factor 5
Chromosome 3 · 3q27.2
NCBI Gene: 2119Ensembl: ENSG00000244405.9HGNC: HGNC:3494UniProt: P41161
100PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription cis-regulatory region bindingRNA polymerase II transcription regulatory region sequence-specific DNA bindingDNA-binding transcription factor activityprotein bindingAbnormality of the skeletal systemobesityobstructive sleep apneadiabetes mellitus
✦AI Summary

ETV5 is a transcription factor that binds DNA sequences containing the consensus core 5'-GGAA-3' motif and functions as both a positive and negative regulator of RNA polymerase II-dependent transcription 1. In lung regeneration, ETV5 signaling promotes alveolar type II cell proliferation while inhibiting differentiation into type I cells 1. In disease contexts, ETV5 demonstrates oncogenic functions across multiple cancer types. In ependymoma, ETV5 enhances repressive chr3 states to promote tumorigenesis and suppresses neuropeptide Y expression 2. In glioblastoma, the IGFBP5-ROR1/HER2-CREB axis induces ETV5 expression to enhance invasion and tumorigenesis 3. In hepatocellular carcinoma, ETV5 transactivates PD-L1 and S100A9 to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells, promoting metastasis and immune escape 4. ETV5 also regulates IRGM-mediated autophagy in esophageal squamous cell carcinoma, contributing to cisplatin resistance 5. Additionally, YTHDF2-mediated translation of ETV5 promotes HCC immune evasion and angiogenesis through PD-L1 and VEGFA induction 6. In ischemic stroke, ETV5 functions as an astrocyte-specific transcription factor associated with oxygen concentration regulation 7. Genetically, ETV5 variants contribute to adiponectin level variability and associated metabolic disease risk 8.

Sources cited
1
ETV5 promotes ependymoma tumorigenesis by enhancing repressive chromatin states and repressing NPY expression
PMID: 39085609
2
ETV5 signaling promotes ATII cell proliferation while inhibiting differentiation to ATI cells during lung regeneration
PMID: 32366033
3
CREB-mediated ETV5 expression downstream of IGFBP5-ROR1/HER2 signaling promotes glioblastoma stem cell invasion
PMID: 36949068
4
ETV5 transactivates PD-L1 and S100A9 to promote HCC metastasis through PMN-MDSC recruitment and immunosuppression
PMID: 40015948
5
ETV5 interaction with KMT2C regulates IRGM-mediated autophagy promoting ESCC progression and cisplatin resistance
PMID: 37705061
6
YTHDF2-facilitated ETV5 translation induces PD-L1 and VEGFA expression promoting HCC immune evasion and angiogenesis
PMID: 38247171
7
ETV5 functions as an astrocyte-specific transcription factor associated with oxygen concentration in ischemic stroke
PMID: 34987704
8
ETV5 genetic variants contribute to circulating adiponectin variability and metabolic disease risk
PMID: 22449616
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.53Moderate
obesityOpen Targets
0.51Moderate
obstructive sleep apneaOpen Targets
0.48Moderate
diabetes mellitusOpen Targets
0.45Moderate
sleep apneaOpen Targets
0.43Moderate
overnutritionOpen Targets
0.42Moderate
morbid obesityOpen Targets
0.40Weak
type 2 diabetes mellitusOpen Targets
0.38Weak
smoking behaviorOpen Targets
0.38Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
gastric carcinomaOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
kidney neoplasmOpen Targets
0.37Weak
lymphoid neoplasmOpen Targets
0.37Weak
Merkel cell skin cancerOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
Pathogenic Variants1
NM_004454.3(ETV5):c.536A>C (p.His179Pro)Pathogenic
Myoepithelial tumor
☆☆☆☆2022→ Residue 179
View on ClinVar ↗
Related Genes
COP1Protein interaction91%DET1Protein interaction91%DUX4Protein interaction86%STK40Protein interaction83%SLC45A3Protein interaction81%GDNFProtein interaction78%
Tissue Expression6 tissues
Lung
100%
Brain
90%
Heart
65%
Liver
50%
Bone Marrow
30%
Ovary
19%
Gene Interaction Network
Click a node to explore
ETV5COP1DET1DUX4STK40SLC45A3GDNF
PROTEIN STRUCTURE
Preparing viewer…
PDB5ILV · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.23Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.08–0.23]
RankingsWhere ETV5 stands among ~20K protein-coding genes
  • #4,778of 20,598
    Most Researched100 · top quartile
  • #4,885of 5,498
    Most Pathogenic Variants1
  • #650of 17,882
    Most Constrained (LOEUF)0.23 · top 5%
Genes detectedETV5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Histone serotonylation regulates ependymoma tumorigenesis.
PMID: 39085609
Nature · 2024
1.00
2
Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration.
PMID: 32366033
Int J Mol Sci · 2020
0.90
3
IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis.
PMID: 36949068
Nat Commun · 2023
0.80
4
E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression.
PMID: 40015948
Gut · 2025
0.70
5
TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM.
PMID: 37705061
Adv Sci (Weinh) · 2023
0.60