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ETV1 (ets variant 1)

Written2013-02Yu Chen, Ping Chi
Human Oncology, Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York, Avenue, New York, NY 10065, USA

(Note : for Links provided by Atlas : click)


Alias_namesets variant gene 1
Alias_symbol (synonym)ER81
Other alias
HGNC (Hugo) ETV1
LocusID (NCBI) 2115
Atlas_Id 73
Location 7p21.2  [Link to chromosome band 7p21]
Location_base_pair Starts at 13891231 and ends at 13990017 bp from pter ( according to hg19-Feb_2009)  [Mapping ETV1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACSL3 (2q36.1) / ETV1 (7p21.2)BMPR1B (4q22.3) / ETV1 (7p21.2)CANT1 (17q25.3) / ETV1 (7p21.2)
ERO1A (14q22.1) / ETV1 (7p21.2)ETV1 (7p21.2) / CPED1 (7q31.31)ETV1 (7p21.2) / ERG (21q22.2)
ETV1 (7p21.2) / EWSR1 (22q12.2)ETV1 (7p21.2) / HMGN2P46 (15q21.1)ETV1 (7p21.2) / HNRNPA2B1 (7p15.2)
ETV1 (7p21.2) / SLC45A3 (1q32.1)ETV1 (7p21.2) / SMG6 (17p13.3)ETV1 (7p21.2) / TMPRSS2 (21q22.3)
ETV1 (7p21.2) / TP53 (17p13.1)EWSR1 (22q12.2) / ETV1 (7p21.2)FOXP1 (3p13) / ETV1 (7p21.2)
FUBP1 (1p31.1) / ETV1 (7p21.2)HMGN2P46 (15q21.1) / ETV1 (7p21.2)HNRNPA2B1 (7p15.2) / ETV1 (7p21.2)
KLK2 (19q13.33) / ETV1 (7p21.2)MIPOL1 (14q13.3) / ETV1 (7p21.2)OR51E2 (11p15.4) / ETV1 (7p21.2)
SLC30A4 (15q21.1) / ETV1 (7p21.2)SLC45A3 (1q32.1) / ETV1 (7p21.2)TMPRSS2 (21q22.3) / ETV1 (7p21.2)


  The ETV1 gene locus is on the p arm of chromosome 7 (7p21.3), spanning from 13930854 to 14031050 (Feb. 2009 GRCh37/hg19).
Description The ETV1 (ETS-translocation variant 1) gene belongs to the PEA3-subfamily of erythroblast transformation-specific (ETS)-family of transcription factors. It is located on chromosome 7p21.3, consisting of 13 exons and spanning approximately 100 kb DNA in length (Coutte et al., 1999).
Transcription ETV1 has 7 Refseq transcripts that are generated by alternative splicing and alternative transcriptional initiation.
Pseudogene No pseudogene reported.


  Schematics of ETV1 and PEA3-subfamily homolog, ETV4 and ETV5. Transcriptional activation acidic domains are in grey and ETS DNA binding domains are in black (adapted from Oh et al., 2012).
Description ETV1 belongs to the PEA3-subfamily of erythroblast transformation-specific (ETS)-family of transcription factors. There are 7 protein isoforms of ETV1, ranging from 374 amino acids to 477 amino acids (~55 kD).
Expression The ETV1 protein is physiologically expressed in the central nervous system including the developing propioceptive neurons, the motor neurons and the dopaminergic neurons (Arber et al., 2000; Flames and Hobert, 2009). ETV1 is also expressed in the inner core cells of the Pacinian corpuscle (Sedy et al., 2006) and in the interstitial cells of Cajal (Chen et al., 2007; Chi et al., 2010). Pathologically, the ETV1 protein is aberrantly expressed in a subset of melanoma and prostate cancer through genomic rearrangements (Jané-Valbuena et al., 2010; Tomlins et al., 2005), or abnormally highly expressed in gastrointestinal stromal tumor (GIST) through high endogenous expression and protein stabilization by active MAP kinase signaling (Chi et al., 2010), or partially highly expressed as part of an oncogenic fusion protein-EWSR1-ETV1-in Ewing sarcoma (Jeon et al., 1995).
Localisation Nucleus.
Function ETV1 belongs to the ETS (E-twenty-six) family of transcription factors and the PEA3 subfamily transcription factors (ETV1, ETV4 and ETV5). It specifically recognizes the GGAA core consensus DNA motif in the genome and mediates transcriptional activation and repression of target genes in cell type and cell lineage-specific contexts. ETV1 is critical in the normal development of a functional sensory-motor circuitry in the spinal cord (Arber et al., 2000), the specification of a group of specialized dopaminergic neurons in the central nervous system (Flames and Hobert, 2009), the normal development of the Pacinian corpuscle (Sedy et al., 2006), and the normal development and specification of the subclasses of interstitial cells of Cajal localized in the circular muscle and in the myenteric plexus (Chi et al., 2010). ETV1 contributes to the pathogenesis of a number of cancer types through 1) aberrantly overexpression in melanoma and prostate cancer via genomic rearrangement (Jané-Valbuena et al., 2010; Tomlins et al., 2007; Tomlins et al., 2005), 2) abnormal protein stabilization in GIST (Chi et al., 2010), 3) formation of the oncogenic fusion protein EWSR1-ETV1 in Ewing sarcoma (Jeon et al., 1995).
Homology A member of the ETS-family transcription factor and the PEA3 subfamily transcription factors , with most sequence homology to ETV5 and ETV4.


Note No validated known mutations.

Implicated in

Entity Ewing sarcoma
Prognosis The prognostic relevance remains to be determined.
Cytogenetics Ewing sarcoma translocation, t(7;22)(p22;q12) that fused EWSR1 to the ETV1 gene (Jeon et al., 1995).
Hybrid/Mutated Gene EWSR1-ETV1 fusion gene accounts for ~1% of all Ewing sarcomas. The majority of Ewing sarcoma fusion genes are EWSR1-FLI1 (~85%) and EWSR1-ERG (~10%).
Abnormal Protein EWSR1-ETV1 fusion protein that fuses the first 7 exons of EWSR1 to the last 3-4 exons of ETV1 (exons 10 or 11-exon 13).
Common breakpoints of the EWS-ETV1 fusion. DNA-BD: DNA binding domain; Pro: proline-rich activation domain; PTD: pointed domain; RGG: arginine-glycine-glycine-rich region; RRM: RNA recognition motif; SYQG: serine-tyrosine-glutamine-glycine-rich region that has a high transactivation potential; ZN: zinc finger. Adapted from Janknecht, 2005.
Oncogenesis The EWSR1-ETS (EWSR1-FLI1, EWSR1-ETV1, EWSR1-ERG, etc) fusion proteins are thought to be the "oncogenic drivers" in Ewing sarcoma. EWSR1-FLI1 and EWSR1-ERG have been modeled in cell lines demonstrating the requirement of the oncogenic fusion proteins for Ewing sarcoma cell line growth and survival. The EWSR1-ETV1 fusion protein has not been modeled.
Entity Prostate cancer
Prognosis ETV1 fusion seems to confer a poorer prognosis in several studies.
Typical breakpoint in prostate cancer fusions.
Oncogenesis ETV1 is aberrantly overexpressed in prostate cancer through genomic rearrangements that result in overexpression of a truncated ETV1 or full-length ETV1. ETV1 is required for the growth of ETV1-positive prostate cancer cells and ETV1 overexpression confers invasiveness prostate cancer cells (Tomlins et al., 2007; Tomlins et al., 2005).
Entity Melanoma
Prognosis The prognostic relevance remains to be determined.
Oncogenesis ETV1 is amplified in 13% of primary and 18% of metastatic melanomas, which results in aberrant overexpression. ETV1 is required for growth and proliferation of melanoma cells with ETV1 amplification and it cooperates with oncogenic NRAS (G12D) for tumorigenesis in mice (Jané-Valbuena et al., 2010).
Entity Gastrointestinal stromal tumor (GIST)
Prognosis The prognostic relevance remains to be determined.
Oncogenesis ETV1 is naturally highly expressed and is required for the development of the interstitial cells of Cajal (ICCs) in the gastrointestinal tract that are the precursor cells of GIST. It is also highly expressed and required for the growth, survival and tumorigenesis of GISTs. It drives a core transcriptional program that is conserved in ICC and GIST. ETV1 protein level is stabilized by active KIT and downstream MAP kinase signaling pathways and cooperates with mutant KIT in GIST pathogenesis (Chi et al., 2010).



To be noted



ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons.
Arber S, Ladle DR, Lin JH, Frank E, Jessell TM.
Cell. 2000 May 26;101(5):485-98.
PMID 10850491
Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine.
Chen H, Ordog T, Chen J, Young DL, Bardsley MR, Redelman D, Ward SM, Sanders KM.
Physiol Genomics. 2007 Nov 14;31(3):492-509. Epub 2007 Sep 25.
PMID 17895395
ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours.
Chi P, Chen Y, Zhang L, Guo X, Wongvipat J, Shamu T, Fletcher JA, Dewell S, Maki RG, Zheng D, Antonescu CR, Allis CD, Sawyers CL.
Nature. 2010 Oct 14;467(7317):849-53. doi: 10.1038/nature09409. Epub 2010 Oct 3.
PMID 20927104
Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human.
Coutte L, Monte D, Imai K, Pouilly L, Dewitte F, Vidaud M, Adamski J, Baert JL, de Launoit Y.
Oncogene. 1999 Nov 4;18(46):6278-86.
PMID 10597226
Gene regulatory logic of dopamine neuron differentiation.
Flames N, Hobert O.
Nature. 2009 Apr 16;458(7240):885-9. doi: 10.1038/nature07929. Epub 2009 Mar 15.
PMID 19287374
An oncogenic role for ETV1 in melanoma.
Jane-Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, Baker AC, Nazarian RM, Vijayendran KG, Sellers WR, Hahn WC, Duncan LM, Rubin MA, Fisher DE, Garraway LA.
Cancer Res. 2010 Mar 1;70(5):2075-84. doi: 10.1158/0008-5472.CAN-09-3092. Epub 2010 Feb 16.
PMID 20160028
EWS-ETS oncoproteins: the linchpins of Ewing tumors.
Janknecht R.
Gene. 2005 Dec 19;363:1-14. Epub 2005 Oct 3.
PMID 16202544
A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.
Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN.
Oncogene. 1995 Mar 16;10(6):1229-34.
PMID 7700648
ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors.
Oh S, Shin S, Janknecht R.
Biochim Biophys Acta. 2012 Aug;1826(1):1-12. doi: 10.1016/j.bbcan.2012.02.002. Epub 2012 Mar 8.
PMID 22425584
ETS transcription factor ER81 is required for the Pacinian corpuscle development.
Sedy J, Tseng S, Walro JM, Grim M, Kucera J.
Dev Dyn. 2006 Apr;235(4):1081-9.
PMID 16493690
Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer.
Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, Menon A, Jing X, Cao Q, Han B, Yu J, Wang L, Montie JE, Rubin MA, Pienta KJ, Roulston D, Shah RB, Varambally S, Mehra R, Chinnaiyan AM.
Nature. 2007 Aug 2;448(7153):595-9.
PMID 17671502


This paper should be referenced as such :
Chen, Y ; Chi, P
ETV1 (ets variant 1)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(7):483-486.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  12p abnormalities in myeloid malignancies
t(8;20)(p11;q13) KAT6A/NCOA3

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 14 ]
  Soft Tissues: Angiomatoid fibrous histiocytoma
Bone tumors: an overview
Soft Tissues: Ewing's tumors/Primitive neurectodermal tumors (PNET)
Prostate tumors: an overview
Soft tissue tumors: an overview
t(1;7)(p31;p21) FUBP1/ETV1
t(4;7)(q22;p21) BMPR1B/ETV1
t(7;7)(p15;p21) HNRNPA2B1/ETV1
t(7;11)(p21;p15) OR51E2/ETV1
t(7;15)(p21;q21) HMGN2P46/ETV1
t(7;17)(p21;p13) HERVK17/ETV1
t(7;17)(p21;p13) AX747630/ETV1
t(7;19)(p21;q13) KLK2/ETV1
t(7;22)(p21;q11) HERVK22Q11/ETV1

External links

HGNC (Hugo)ETV1   3490
Entrez_Gene (NCBI)ETV1  2115  ETS variant 1
GeneCards (Weizmann)ETV1
Ensembl hg19 (Hinxton)ENSG00000006468 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000006468 [Gene_View]  ENSG00000006468 [Sequence]  chr7:13891231-13990017 [Contig_View]  ETV1 [Vega]
ICGC DataPortalENSG00000006468
TCGA cBioPortalETV1
AceView (NCBI)ETV1
Genatlas (Paris)ETV1
SOURCE (Princeton)ETV1
Genetics Home Reference (NIH)ETV1
Genomic and cartography
GoldenPath hg38 (UCSC)ETV1  -     chr7:13891231-13990017 -  7p21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ETV1  -     7p21.2   [Description]    (hg19-Feb_2009)
EnsemblETV1 - 7p21.2 [CytoView hg19]  ETV1 - 7p21.2 [CytoView hg38]
Mapping of homologs : NCBIETV1 [Mapview hg19]  ETV1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB209202 AF070641 AK055368 AK293802 AK294572
RefSeq transcript (Entrez)NM_001163147 NM_001163148 NM_001163149 NM_001163150 NM_001163151 NM_001163152 NM_004956
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ETV1
Cluster EST : UnigeneHs.574240 [ NCBI ]
CGAP (NCI)Hs.574240
Alternative Splicing GalleryENSG00000006468
Gene ExpressionETV1 [ NCBI-GEO ]   ETV1 [ EBI - ARRAY_EXPRESS ]   ETV1 [ SEEK ]   ETV1 [ MEM ]
Gene Expression Viewer (FireBrowse)ETV1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2115
GTEX Portal (Tissue expression)ETV1
Human Protein AtlasENSG00000006468-ETV1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP50549   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP50549  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP50549
Splice isoforms : SwissVarP50549
Domaine pattern : Prosite (Expaxy)ETS_DOMAIN_1 (PS00345)    ETS_DOMAIN_2 (PS00346)    ETS_DOMAIN_3 (PS50061)   
Domains : Interpro (EBI)Ets_dom    ETS_PEA3_N    ETS_V1    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)Ets (PF00178)    ETS_PEA3_N (PF04621)   
Domain families : Pfam (NCBI)pfam00178    pfam04621   
Domain families : Smart (EMBL)ETS (SM00413)  
Conserved Domain (NCBI)ETV1
DMDM Disease mutations2115
Blocks (Seattle)ETV1
PDB (SRS)4AVP    4BNC   
PDB (PDBSum)4AVP    4BNC   
PDB (IMB)4AVP    4BNC   
Structural Biology KnowledgeBase4AVP    4BNC   
SCOP (Structural Classification of Proteins)4AVP    4BNC   
CATH (Classification of proteins structures)4AVP    4BNC   
Human Protein Atlas [tissue]ENSG00000006468-ETV1 [tissue]
Peptide AtlasP50549
IPIIPI00306430   IPI00221065   IPI00892613   IPI00893973   IPI00893217   IPI00744316   IPI00892747   IPI00892607   IPI00894345   IPI00894180   IPI00894082   
Protein Interaction databases
IntAct (EBI)P50549
Ontologies - Pathways
Ontology : AmiGORNA polymerase II proximal promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding  DNA binding transcription factor activity  protein binding  nucleus  transcription by RNA polymerase II  axon guidance  muscle organ development  mechanosensory behavior  positive regulation of transcription by RNA polymerase II  peripheral nervous system neuron development  
Ontology : EGO-EBIRNA polymerase II proximal promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding  DNA binding transcription factor activity  protein binding  nucleus  transcription by RNA polymerase II  axon guidance  muscle organ development  mechanosensory behavior  positive regulation of transcription by RNA polymerase II  peripheral nervous system neuron development  
NDEx NetworkETV1
Atlas of Cancer Signalling NetworkETV1
Wikipedia pathwaysETV1
Orthology - Evolution
GeneTree (enSembl)ENSG00000006468
Phylogenetic Trees/Animal Genes : TreeFamETV1
Homologs : HomoloGeneETV1
Homology/Alignments : Family Browser (UCSC)ETV1
Gene fusions - Rearrangements
Fusion : Mitelman-/7p21.2 [ETV1/t(7;14)(p21;q21)|t(7;17)(p21;p13)|t(7;22)(p21;q11)]  
Fusion : MitelmanACSL3/ETV1 [2q36.1/7p21.2]  [t(2;7)(q36;p21)]  
Fusion : MitelmanBMPR1B/ETV1 [4q22.3/7p21.2]  [t(4;7)(q22;p21)]  
Fusion : MitelmanEWSR1/ETV1 [22q12.2/7p21.2]  [t(7;22)(p21;q12)]  
Fusion : MitelmanFOXP1/ETV1 [3p13/7p21.2]  [t(3;7)(p13;p21)]  
Fusion : MitelmanFUBP1/ETV1 [1p31.1/7p21.2]  [t(1;7)(p31;p21)]  
Fusion : MitelmanHMGN2P46/ETV1 [15q21.1/7p21.2]  [t(7;15)(p21;q21)]  
Fusion : MitelmanHNRNPA2B1/ETV1 [7p15.2/7p21.2]  [t(7;7)(p15;p21)]  
Fusion : MitelmanKLK2/ETV1 [19q13.33/7p21.2]  [t(7;19)(p21;q13)]  
Fusion : MitelmanOR51E2/ETV1 [11p15.4/7p21.2]  [t(7;11)(p21;p15)]  
Fusion : MitelmanSLC45A3/ETV1 [1q32.1/7p21.2]  [t(1;7)(q32;p21)]  
Fusion : MitelmanTMPRSS2/ETV1 [21q22.3/7p21.2]  [del(21)(q22q22)]  [t(17;21)(q21;q22)]  
[t(21;21)(q22;q22)]  [t(7;21)(p21;q22)]  
Fusion : COSMICACSL3 [2q36.1]  -  ETV1 [7p21.2]  [fusion_1125]  [fusion_1126]  
Fusion : COSMICEWSR1 [22q12.2]  -  ETV1 [7p21.2]  [fusion_163]  [fusion_164]  [fusion_197]  
Fusion : COSMICHNRNPA2B1 [7p15.2]  -  ETV1 [7p21.2]  [fusion_1121]  [fusion_1122]  [fusion_1129]  
Fusion : COSMICKLK2 [19q13.33]  -  ETV1 [7p21.2]  [fusion_1116]  [fusion_1117]  [fusion_1118]  
Fusion : COSMICSLC45A3 [1q32.1]  -  ETV1 [7p21.2]  [fusion_1119]  [fusion_1120]  [fusion_1130]  
Fusion : COSMICTMPRSS2 [21q22.3]  -  ETV1 [7p21.2]  [fusion_115]  [fusion_122]  [fusion_134]  [fusion_14]  [fusion_15]  [fusion_22]  [fusion_33]  
Fusion PortalBMPR1B 4q22.3 ETV1 7p21.2 PRAD
Fusion : TICdbACSL3 [2q36.1]  -  ETV1 [7p21.2]
Fusion : TICdbERVK-17 [-]  -  ETV1 [7p21.2]
Fusion : TICdbEWSR1 [22q12.2]  -  ETV1 [7p21.2]
Fusion : TICdbHMGN2P46 [15q21.1]  -  ETV1 [7p21.2]
Fusion : TICdbTMPRSS2 [21q22.3]  -  ETV1 [7p21.2]
Fusion : QuiverETV1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerETV1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ETV1
Exome Variant ServerETV1
ExAC (Exome Aggregation Consortium)ENSG00000006468
GNOMAD BrowserENSG00000006468
Genetic variants : HAPMAP2115
Genomic Variants (DGV)ETV1 [DGVbeta]
DECIPHERETV1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisETV1 
ICGC Data PortalETV1 
TCGA Data PortalETV1 
Broad Tumor PortalETV1
OASIS PortalETV1 [ Somatic mutations - Copy number]
Cancer Gene: CensusETV1 
Somatic Mutations in Cancer : COSMICETV1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDETV1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ETV1
DgiDB (Drug Gene Interaction Database)ETV1
DoCM (Curated mutations)ETV1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ETV1 (select a term)
NCG5 (London)ETV1
Cancer3DETV1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry ETV1
NextProtP50549 [Medical]
Target ValidationETV1
Huge Navigator ETV1 [HugePedia]
snp3D : Map Gene to Disease2115
BioCentury BCIQETV1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2115
Chemical/Pharm GKB GenePA27904
Clinical trialETV1
canSAR (ICR)ETV1 (select the gene name)
PubMed86 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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