ETV2 (ETS Variant Transcription Factor 2): A Master Regulator of Hematopoietic and Endothelial Development
Explore the genomic architecture, expression patterns, disease associations, and functional classification of ETV2, a pioneer transcription factor essential for vascular and blood cell formation.
Gene Information Card
| Symbol | ETV2 |
|---|---|
| Full Name | ETS variant transcription factor 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 19q13.12 (GRCh38) |
| NCBI Gene ID | 2116 ncbi.nlm.nih.gov/gene/2116 |
| Ensembl ID | ENSG00000105664 |
| UniProt ID | Q8N9G5 |
| OMIM ID | 612314 |
| HGNC ID | 3487 |
| Aliases | ER71, ETS-related protein 71 |
Description
ETV2 (ETS variant transcription factor 2) is a member of the ETS family of transcription factors, characterized by a conserved ETS DNA-binding domain. It is a pioneer transcription factor that plays a critical role in the specification of hematopoietic and endothelial lineages during embryonic development. ETV2 is transiently expressed in early mesoderm and is essential for the formation of blood and vascular endothelial cells. It regulates the expression of key genes involved in angiogenesis, vasculogenesis, and hematopoiesis. In adults, ETV2 is largely silenced, but its reactivation has been implicated in certain cancers and vascular repair mechanisms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coronary artery disease (CAD) | ETV2 variants may affect endothelial function and vascular repair, contributing to CAD susceptibility. | ClinVar: rs147641903 (missense variant) with uncertain significance for CAD. |
| Peripheral arterial disease (PAD) | ETV2 expression is associated with endothelial regeneration; reduced function may impair collateral vessel formation. | PubMed studies (PMID: 27378309) show ETV2 promotes endothelial reprogramming in ischemic tissues. |
| Hereditary hemorrhagic telangiectasia (HHT)-like phenotype | ETV2 mutations may disrupt endothelial cell differentiation, leading to vascular malformations. | Case reports in ClinVar (e.g., c.4A>G, p.Ser2Gly) with uncertain significance. |
| Cancer (various) | ETV2 is aberrantly expressed in some tumors, potentially driving angiogenesis and tumor progression. | COSMIC: ETV2 mutations found in melanoma, lung, and colorectal cancers (frequency <1%). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
| Thyroid | 0.0 | Not detected |
| Adipose | 0.0 | Not detected |
| Skin | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (Human Umbilical Vein Endothelial Cells) | 0.0 | ETV2 is not expressed in mature endothelial cells; it is only transiently active during development. |
| K562 (Chronic Myelogenous Leukemia) | 0.0 | No expression; ETV2 is silenced in adult hematopoietic cells. |
| MCF7 (Breast Cancer) | 0.0 | Low/absent expression; not a typical cancer line for ETV2. |
| A549 (Lung Cancer) | 0.0 | No expression; ETV2 is not commonly expressed in adult tissues. |
| HEK293 (Embryonic Kidney) | 0.0 | No expression; ETV2 is not active in this cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4A>G (p.Ser2Gly) | Missense | Rare (MAF <0.01%) | Uncertain significance; may affect protein stability or function. |
| c.113C>T (p.Pro38Leu) | Missense | Rare | Uncertain significance; located in the ETS domain, potentially affecting DNA binding. |
| c.244G>A (p.Glu82Lys) | Missense | Rare | Uncertain significance; may alter transcriptional activity. |
| c.331C>T (p.Arg111Trp) | Missense | Rare | Uncertain significance; possible loss-of-function effect. |
| c.412A>G (p.Ile138Val) | Missense | Rare | Uncertain significance; no known disease association. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ETV2 are expected to impair endothelial and hematopoietic differentiation. In model organisms, ETV2 knockout leads to embryonic lethality due to lack of blood vessels. In humans, such mutations are rare and may contribute to vascular defects, but no definitive pathogenic variants have been established.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized. Overexpression of ETV2 in adult cells can reprogram them toward endothelial fate, suggesting that activating mutations could promote angiogenesis, but no such mutations have been reported in human disease.
Dominant Negative (DN)
Dominant-negative effects are possible if a mutant ETV2 protein retains DNA-binding ability but lacks transactivation domain, interfering with wild-type function. However, no dominant-negative mutations have been documented in ClinVar or literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ETS transcription factor pathway
• VEGF signaling pathway (regulation of endothelial development)
• Notch signaling pathway (cross-talk in vascular development)
• Hematopoietic stem cell differentiation pathway
Protein Summary
ETV2 is a 371-amino acid protein with a molecular weight of approximately 41 kDa. It contains a highly conserved ETS DNA-binding domain (residues 1-90) that recognizes the consensus sequence 5'-GGAA-3'. The protein also has a transactivation domain in the C-terminal region. ETV2 functions as a pioneer factor, opening chromatin at target gene loci to initiate transcriptional programs for endothelial and hematopoietic specification. It interacts with other transcription factors such as GATA2 and FLI1 to regulate downstream genes. In adult tissues, ETV2 is epigenetically silenced, but its ectopic expression can induce endothelial reprogramming, making it a potential therapeutic target for vascular regeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ETV2 Knockout HEK293 Cell Line | EDJ-KQ2697 | Human | 2116 | Details Get a Quote |
| ETV2 Knockout HeLa Cell Line | EDJ-KQ22155 | Human | 2116 | Details Get a Quote |
| ETV2 Knockout A-549 Cell Line | EDJ-KQ23528 | Human | 2116 | Details Get a Quote |
| ETV2 Knockout HCT 116 Cell Line | EDJ-KQ23529 | Human | 2116 | Details Get a Quote |
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