ETV1

Chr 7

ETS variant transcription factor 1

Also known as: ER81

NCBI Gene: 2115ENSG00000006468UniProt: P50549

This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

UniProtEwing sarcoma
1
Active trials
31
Pathogenic / LP
110
ClinVar variants
34
Pubs (1 yr)
0.9
Missense Z
0.35
LOEUF· LoF intolerant
Clinical Summary— ETV1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 77 VUS of 110 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.937
Z-score 4.04
OE 0.15 (0.07–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.87Z-score
OE missense 0.85 (0.76–0.95)
229 obs / 269.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.07–0.35)
0≤0.351.4
Missense OE0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 4 / 26.4Missense obs/exp: 229 / 269.4Syn Z: -2.28
LOF
DN
0.5378th %ile
GOF
0.2298th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic2
VUS77
Likely Benign2
29
Pathogenic
2
Likely Pathogenic
77
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
2
0
2
VUS
0
66
11
0
77
Likely Benign
0
0
2
0
2
Benign
0
0
0
0
0
Total066440110

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

ETV1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Development and characterization of an ETV1 rabbit monoclonal antibody for the immunohistochemical detection of ETV1 expression in cancer tissue specimens
Schafer C et al.·J Immunol Methods
2023
Novel ETV1 mutation in small cell lung cancer transformation resistant to EGFR tyrosine kinase inhibitors
Zhou Y et al.·Ann Transl Med
2021
HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET
Zhang T et al.·J Exp Clin Cancer Res
2022
EGFR-STAT3 activation provides a therapeutic rationale for targeting aggressive ETV1-positive prostate cancer
Paiva EG et al.·Mol Oncol
2025
SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
Proaño-Pérez E et al.·Cancers (Basel)
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients