ETV1

Summary

ETV1 (ETS variant transcription factor 1, HGNC:3490) is a protein-coding gene on chromosome 7p21.2, encoding ETS translocation variant 1 (P50549). Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5’-CGGA[AT]-3'.

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.

Source: NCBI Gene 2115 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 87 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Transcription factor: yes — 22 downstream targets (CollecTRI)
• MANE Select transcript: NM_004956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3490
Approved symbol	ETV1
Name	ETS variant transcription factor 1
Location	7p21.2
Locus type	gene with protein product
Status	Approved
Aliases	ER81
Ensembl gene	ENSG00000006468
Ensembl biotype	protein_coding
OMIM	600541
Entrez	2115

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 18 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000242066, ENST00000403527, ENST00000403685, ENST00000405192, ENST00000405218, ENST00000405358, ENST00000421381, ENST00000430479, ENST00000431887, ENST00000433547, ENST00000438956, ENST00000443137, ENST00000443608, ENST00000460438, ENST00000472931, ENST00000476355, ENST00000476720, ENST00000483075, ENST00000485475, ENST00000493831, ENST00000497115, ENST00000897798, ENST00000970556, ENST00000970557, ENST00000970558, ENST00000970559, ENST00000970560

RefSeq mRNA: 9 — MANE Select: NM_004956 NM_001163147, NM_001163148, NM_001163149, NM_001163150, NM_001163151, NM_001163152, NM_001370555, NM_001370556, NM_004956

CCDS: CCDS55083, CCDS55084, CCDS55085, CCDS55086, CCDS55087, CCDS55088

Canonical transcript exons

ENST00000430479 — 14 exons

Exon	Start	End
ENSE00001537799	13989268	13989464
ENSE00001554755	13891229	13896087
ENSE00001625577	13989563	13989666
ENSE00003465794	13900738	13900839
ENSE00003499933	13989008	13989139
ENSE00003515391	13977427	13977480
ENSE00003595382	13935708	13935896
ENSE00003600886	13931502	13931749
ENSE00003606614	13986638	13986685
ENSE00003613528	13939117	13939246
ENSE00003662173	13911239	13911307
ENSE00003671672	13906430	13906599
ENSE00003687305	13909632	13909700
ENSE00003694454	13988086	13988173

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2116 / max 783.7972, expressed in 1201 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82826	9.0093	1153
82819	1.3781	417
82822	1.0753	406
82827	0.9400	447
82814	0.2993	84
82825	0.2911	131
82812	0.2841	75
82815	0.1977	49
82810	0.1958	44
82824	0.1785	55

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.77	gold quality
parotid gland	UBERON:0001831	98.00	gold quality
cerebellum	UBERON:0002037	97.67	gold quality
cerebellar cortex	UBERON:0002129	97.67	gold quality
cerebellar hemisphere	UBERON:0002245	97.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.95	gold quality
visceral pleura	UBERON:0002401	96.71	gold quality
lower lobe of lung	UBERON:0008949	95.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.35	gold quality
adrenal tissue	UBERON:0018303	92.99	gold quality
paraflocculus	UBERON:0005351	92.82	gold quality
heart right ventricle	UBERON:0002080	91.25	gold quality
ventricular zone	UBERON:0003053	91.23	gold quality
right lung	UBERON:0002167	90.87	gold quality
cortical plate	UBERON:0005343	90.32	gold quality
islet of Langerhans	UBERON:0000006	90.30	gold quality
gall bladder	UBERON:0002110	90.29	gold quality
adult organism	UBERON:0007023	89.67	gold quality
lung	UBERON:0002048	89.60	gold quality
pleura	UBERON:0000977	88.72	gold quality
CA1 field of hippocampus	UBERON:0003881	88.19	gold quality
myocardium	UBERON:0002349	87.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.83	gold quality
pons	UBERON:0000988	87.79	gold quality
ganglionic eminence	UBERON:0004023	87.42	gold quality
upper lobe of lung	UBERON:0008948	87.13	gold quality
heart left ventricle	UBERON:0002084	87.10	gold quality
cardiac ventricle	UBERON:0002082	87.01	gold quality
entorhinal cortex	UBERON:0002728	87.01	gold quality
upper lobe of left lung	UBERON:0008952	86.54	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	810.96
E-GEOD-83139	yes	598.36
E-GEOD-81608	yes	487.02
E-MTAB-5061	yes	486.99
E-ENAD-27	yes	424.63
E-ANND-3	yes	21.28
E-HCAD-31	yes	9.46
E-GEOD-125970	yes	6.59
E-GEOD-93593	yes	5.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

22 targets.

Target	Regulation
AR	Unknown
CAT	Unknown
CDKN2A
DNPH1	Unknown
DYM	Activation
ERBB2	Unknown
FGF10	Unknown
GRIN2C	Activation
HES5	Repression
MMP1	Unknown
MMP3	Unknown
MMP7	Activation
MUC4	Activation
NAB2	Activation
PLAU	Activation
POMC	Unknown
PSEN1	Activation
SMAD7	Unknown
TERT	Unknown
TGFBR2	Activation
TH
TIAM1	Activation

JASPAR motifs

Motif	Name	Family
MA0761.1	ETV1	Ets-related
MA0761.2	ETV1	Ets-related
MA0761.3	ETV1	Ets-related
MA1966.1	TFAP4::ETV1	bHLH-ZIP::Ets-related
MA1966.2	TFAP4::ETV1	bHLH-ZIP::Ets-related

JASPAR matrix evidence (PMIDs): PMID:20517297, PMID:25866208, PMID:24218641

Upstream regulators (CollecTRI, top): AR, JUN, NEUROG2, PAX6

miRNA regulators (miRDB)

268 targeting ETV1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 40)

• ER81 is acetylated by two coactivators/acetyltransferases, p300 and p300- and CBP-associated factor (P/CAF) . Whereas p300 acetylates two lysine residues (K33 and K116) within the ER81 N-terminal transactivation domain, P/CAF targets only K116. (PMID:12917345)
• attenuation of transforming growth factor-beta signaling by activating Smad7 transcription may proceed not only through TGF-beta receptor-regulated Smad proteins but also an independent pathway involving transcription factor ER81 and TAK1 protein kinase (PMID:12947087)
• transcription factor ER81 is regulated by oncogenic HER2/Neu and ACTR in mammary tumorigenesis (PMID:14747462)
• demonstrate for the first time that the TMPRSS2-ERG fusion gene can be detected in a proportion of HGPIN lesions and that this molecular rearrangement is an early event that may precede chromosome-level alterations in prostate carcinogenesis (PMID:17032499)
• findings show that the TMPRSS2-ERG fusion is common in prostate cancer and that the related TMPRSS2-ETV1 fusion is very rare (PMID:17390040)
• Expression transitions from androgen-induced to androgen-independent as prostate cancer cells switch from hormone-dependent to hormone-refractory. (PMID:17505060)
• TMPRSS2-ERV1 fusion protein was found in 1/82 prostate neoplasms. (PMID:17632455)
• These results imply that c-Jun plays a pivotal role in the pathway that connects ligand-activated AR to elevated ETV1 expression, leading to enhanced expression of matrix metalloproteinases and prostate cancer cell invasion. (PMID:17634427)
• Detection of ETS fusion gene by RT-PCR is feasible on formalin-fixed and paraffin-embedded samples. (PMID:18474293)
• Studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer. (PMID:18594527)
• Sox-9, ER81 and VE-cadherin have roles in retinoic acid-mediated trans-differentiation of breast cancer cells (PMID:18628953)
• ETV1 and HER2/Neu synergized to upregulate the endogenous Rcl gene. ETV1 also bound to the Rcl promoter. (PMID:18726892)
• 1% histologic variant of prostate carcinoma or variation morphologies demonstrated ETV! aberrations (PMID:19465903)
• Transcriptional activation of hTERT in breast carcinomas by the Her2-ER81-related pathway. (PMID:19718948)
• Overexpression of ETV1 is associated with tha induction of prostatic intraepithelial neoplasia. (PMID:19789348)
• ERG/ETV1 gene rearrangements and PTEN gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved. (PMID:20104229)
• Melanoma cell lines, including those with ETV1 amplification, exhibited dependency on ETV1 expression for proliferation and anchorage-independent growth. (PMID:20160028)
• the ETS family member ETV1 is highly expressed in the subtypes of interstitial cells of Cajal sensitive to oncogenic KIT mediated transformation, and is required for their development (PMID:20927104)
• in clinical prostate cancer overexpression of full-length ETV1 is due to genomic rearrangements involving different chromosomes (PMID:21298110)
• ERG and ETV1 mediated prostate cancer cell invasion is inhibited by YK-4-279 (PMID:21559405)
• The coordinate expression of Etv1 with POMC cell differentiation and its interaction with the highly cell-restricted Tpit factor indicate that Etv1 participates in a combinatorial code for pituitary cell-specific gene expression. (PMID:21622576)
• High ER81 expression is associated with gastric adenocarcinoma. (PMID:21673681)
• Pea3 and Erm, but not Er81, play an important role in the progression of esophageal squamous cell carcinoma (PMID:21689625)
• Data show that MAPKAP kinase 2 overexpression is associated with expression of p38 MAP kinase and ETV1 in gastrointestinal stromal tumors (GIST). (PMID:22351694)
• Reviews evidence for a role of ETV1, 4 and 5 as oncoproteins and describe modes of their action. (PMID:22425584)
• High ER81 expression is associated with breast cancer. (PMID:22901226)
• High ETV1 expression is associated with prostate cancer. (PMID:23076342)
• Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells (PMID:23284306)
• confirmed the association of an ETV1 expression signature with aggressive disease and poorer outcome in patient data (PMID:23512661)
• Proprioceptive sensory neurons innervating hypaxial and axial muscles depend critically on Etv1 for survival. (PMID:23522042)
• Non-sigma 14-3-3 proteins synergized with ETV1 to activate transcription. (PMID:23774214)
• Expression of ERG and ETV1 correlated with higher AR transcriptional output in PTEN-deficient prostate cancer specimens. (PMID:23817021)
• The gastrointestinal stromal tumor-specific transcription factor ETV1 may have no prognostic potential, whereas its downstream gene KCTD10 is associated with a favorable prognosis. (PMID:23977394)
• ETV1 expression is significantly correlated with Snail expression in human gastric tumor samples. In summary, we present data that ETV1 promotes Snail expression to induce EMT-like metastatic progression in gastric cancer. (PMID:24100634)
• Elevated levels of either wild-type ETV1 or its truncated derivative, dETV1, which mimics the product of an oncogenic rearrangement in certain tumors, results in increased expression of mRNA for p14ARF, a known activator of p53. (PMID:24157551)
• These results point to a new avenue for pharmacologic ETV1 inhibition and may inform a general means to discover small molecule perturbagens of transcription factor oncoproteins. (PMID:24737027)
• Results show that ETV1 was upregulated at a higher rate in Gastrointestinal stromal tumor and was correlated with KIT expression. (PMID:24970355)
• ETV1 expression is a rare event in human melanoma and seems to be rather based on hyperactivation of MAPK signals, by BRAF (V600E) mutation, than on ETV1 gene amplification. (PMID:25073704)
• developed a novel RNA in situ hybridization-based assay for the in situ detection of ETV1, ETV4, and ETV5 in formalin-fixed paraffin-embedded tissues from prostate needle biopsies, prostatectomy, and metastatic PCa specimens using RNA probes (PMID:25203299)
• YK-4-279 is a potent inhibitor of ETV1 and inhibits both the primary tumor growth and metastasis of fusion positive prostate cancer xenografts. (PMID:25479232)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	etv1	ENSDARG00000101959
mus_musculus	Etv1	ENSMUSG00000004151
rattus_norvegicus	Etv1	ENSRNOG00000006867

Paralogs (28): ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS translocation variant 1 — P50549 (reviewed: P50549)

Alternative names: Ets-related protein 81

All UniProt accessions (8): P50549, B5MCT2, C9J0B7, C9J4P4, C9J9L1, C9JQH6, C9JX69, F8WEH6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5’-CGGA[AT]-3’. Required for olfactory dopaminergic neuron differentiation; may directly activate expression of tyrosine hydroxylase (TH).

Subcellular location. Nucleus.

Tissue specificity. Very highly expressed in brain, highly expressed in testis, lung and heart, moderately in spleen, small intestine, pancreas and colon, weakly in liver, prostate and thymus, very weakly in skeletal muscle, kidney and ovary and not in placenta and peripheral blood leukocytes.

Post-translational modifications. Sumoylated. Phosphorylated at Ser-191 and Ser-216 by RPS6KA1 and RPS6KA5; phosphorylation activates transcriptional activity.

Disease relevance. Ewing sarcoma (ES) [MIM:612219] A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV1 is found in patients with Ewing sarcoma. Translocation t(7;22)(p22;q12) with EWSR1.

Similarity. Belongs to the ETS family.

Isoforms (6)

UniProt ID	Names	Canonical?
P50549-1	1	yes
P50549-2	2
P50549-3	3
P50549-4	4
P50549-5	5
P50549-6	6

RefSeq proteins (9): NP_001156619, NP_001156620, NP_001156621, NP_001156622, NP_001156623, NP_001156624, NP_001357484, NP_001357485, NP_004947* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR006715	ETS_PEA3_N	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178, PF04621

UniProt features (31 total): sequence conflict 7, helix 5, splice variant 4, strand 4, modified residue 3, mutagenesis site 2, chain 1, DNA-binding region 1, sequence variant 1, region of interest 1, turn 1, cross-link 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5ILS	X-RAY DIFFRACTION	1.4
4AVP	X-RAY DIFFRACTION	1.82
4BNC	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50549-F1	58.90	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 94, 191, 216, 317

Mutagenesis-validated functional residues (2):

Position	Phenotype
191	loss of phosphorylation by rps6ka5.
216	loss of phosphorylation by rps6ka5.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 357 (showing top): CHOI_ATL_ACUTE_STAGE, CREL_01, RRAGTTGT_UNKNOWN, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_BEHAVIOR, LFA1_Q6, GCANCTGNY_MYOD_Q6, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_NEUROGENESIS, FOXO4_01, FOXO1_01, CHX10_01, USF_C, CAGCTG_AP4_Q5, YY1_Q6

GO Biological Process (10): regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), axon guidance (GO:0007411), muscle organ development (GO:0007517), mechanosensory behavior (GO:0007638), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), peripheral nervous system neuron development (GO:0048935), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
axonogenesis	1
neuron projection guidance	1
animal organ development	1
muscle structure development	1
behavior	1
response to mechanical stimulus	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
neuron development	1
peripheral nervous system neuron differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETV1	TMPRSS2	O15393	942
ETV1	SLC45A3	Q96JT2	891
ETV1	AR	P10275	884
ETV1	EWSR1	Q01844	883
ETV1	DUX4L2	P0CJ85	787
ETV1	KIT	P10721	772
ETV1	FUS	P35637	749
ETV1	TP53	P04637	627
ETV1	PATZ1	Q9HBE1	622
ETV1	CD99	P14209	617
ETV1	GOT1	P17174	610
ETV1	SPOP	O43791	604
ETV1	HNRNPA2B1	P22626	586
ETV1	FOXA1	P55317	576
ETV1	KLK2	P20151	567

IntAct

49 interactions, top by confidence:

A	B	Type	Score
ETV1		psi-mi:“MI:0407”(direct interaction)	0.590
	ETV1	psi-mi:“MI:0407”(direct interaction)	0.590
	ETV1	psi-mi:“MI:0914”(association)	0.590
NFE2L2	ETV1	psi-mi:“MI:0915”(physical association)	0.580
COP1	ETV1	psi-mi:“MI:0915”(physical association)	0.560
ETV1	PRKDC	psi-mi:“MI:0407”(direct interaction)	0.520
SPOP	ETV1	psi-mi:“MI:2364”(proximity)	0.470
ETV1	SPOP	psi-mi:“MI:2364”(proximity)	0.470
SPOP	ETV1	psi-mi:“MI:0915”(physical association)	0.470
COP1	ETS2	psi-mi:“MI:0914”(association)	0.460
	ETV1	psi-mi:“MI:0915”(physical association)	0.400
	ETV1	psi-mi:“MI:0915”(physical association)	0.370
CCL2	ETV1	psi-mi:“MI:0915”(physical association)	0.370
CCL26	ETV1	psi-mi:“MI:0915”(physical association)	0.370
IL23A	ETV1	psi-mi:“MI:0915”(physical association)	0.370
IL36A	ETV1	psi-mi:“MI:0915”(physical association)	0.370
TNFSF4	ETV1	psi-mi:“MI:0915”(physical association)	0.370
ETV1	CCND3	psi-mi:“MI:0915”(physical association)	0.370
ETV1	rep	psi-mi:“MI:0915”(physical association)	0.370
ETV1	PARP1	psi-mi:“MI:0914”(association)	0.350
ETV1	DET1	psi-mi:“MI:0914”(association)	0.350
COP1	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): NCOA3 (Affinity Capture-Western), ETV1 (Biochemical Activity), ETV1 (Biochemical Activity), ETV1 (Biochemical Activity), ETV1 (Reconstituted Complex), ETV1 (Biochemical Activity), STK40 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), DET1 (Affinity Capture-MS), ETV1 (Synthetic Growth Defect), TERT (Dosage Rescue), ETV1 (Affinity Capture-Western), ETV1 (Biochemical Activity), ETV1 (Dosage Rescue), ETV1 (Dosage Rescue)

ESM2 similar proteins: A0PJS5, A3KNX5, A8K830, F8VPY8, O54968, P01102, P01105, P12979, P15173, P28322, P41161, P41164, P43268, P49812, P50549, P53450, Q14140, Q16633, Q29RM2, Q2KIC2, Q2KJA4, Q4G112, Q56TN0, Q56TT7, Q5M7N6, Q5M9G5, Q5R815, Q5ZKN5, Q60795, Q64693, Q66IT9, Q6NYT3, Q6PB51, Q6PBC9, Q7YR76, Q7YS81, Q80V38, Q80VF6, Q8BGR5, Q8BXQ8

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
MAPKAPK2	up-regulates	ETV1	phosphorylation
RPS6KA1	“up-regulates activity”	ETV1	phosphorylation
RPS6K	“up-regulates activity”	ETV1	phosphorylation
RPS6KA5	“up-regulates activity”	ETV1	phosphorylation
ATR	“up-regulates quantity by stabilization”	ETV1	phosphorylation
PRKACA	“up-regulates activity”	ETV1	phosphorylation
PRKACA	up-regulates	ETV1	phosphorylation
MAPKAPK2	“down-regulates activity”	ETV1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
inflammatory response	7	11.5×	3e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	5	11.3×	2e-03
protein ubiquitination	6	10.8×	9e-04
positive regulation of gene expression	6	10.1×	1e-03
negative regulation of apoptotic process	5	7.5×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — BRCA, COAD.

Clinical variants and AI predictions

ClinVar

87 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1320278	GRCh37/hg19 7p21.3-21.2(chr7:8980970-14085991)x3	Likely pathogenic

SpliceAI

2368 predictions. Top by Δscore:

Variant	Effect	Δscore
7:13895877:AG:A	donor_gain	1.0000
7:13895878:G:C	donor_gain	1.0000
7:13900732:GCTCA:G	donor_loss	1.0000
7:13900733:CTCAC:C	donor_loss	1.0000
7:13900734:TCA:T	donor_loss	1.0000
7:13900735:CACC:C	donor_loss	1.0000
7:13900736:ACC:A	donor_loss	1.0000
7:13900737:C:CG	donor_loss	1.0000
7:13909697:CAGC:C	acceptor_gain	1.0000
7:13909701:C:CC	acceptor_gain	1.0000
7:13935902:C:T	acceptor_gain	1.0000
7:13935903:A:T	acceptor_gain	1.0000
7:13939243:GCCA:G	acceptor_gain	1.0000
7:13939244:CCA:C	acceptor_gain	1.0000
7:13939244:CCAC:C	acceptor_gain	1.0000
7:13939245:CA:C	acceptor_gain	1.0000
7:13939245:CAC:C	acceptor_gain	1.0000
7:13939247:C:CC	acceptor_gain	1.0000
7:13952894:T:TA	donor_gain	1.0000
7:13977417:CTATA:C	donor_gain	1.0000
7:13977425:A:AC	donor_gain	1.0000
7:13977426:C:CC	donor_gain	1.0000
7:13977426:CA:C	donor_gain	1.0000
7:13977426:CAA:C	donor_gain	1.0000
7:13977426:CAACT:C	donor_gain	1.0000
7:13977476:CTGAG:C	acceptor_gain	1.0000
7:13977481:C:CC	acceptor_gain	1.0000
7:13986683:GTT:G	acceptor_gain	1.0000
7:13986684:TT:T	acceptor_gain	1.0000
7:13986685:TC:T	acceptor_loss	1.0000

AlphaMissense

3196 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:13896038:A:G	L421P	1.000
7:13896038:A:T	L421H	1.000
7:13896052:A:C	C416W	1.000
7:13896053:C:T	C416Y	1.000
7:13896054:A:G	C416R	1.000
7:13896058:A:C	F414L	1.000
7:13896058:A:T	F414L	1.000
7:13896059:A:C	F414C	1.000
7:13896059:A:G	F414S	1.000
7:13896060:A:C	F414V	1.000
7:13896060:A:G	F414L	1.000
7:13896060:A:T	F414I	1.000
7:13896061:C:A	K413N	1.000
7:13896061:C:G	K413N	1.000
7:13896063:T:C	K413E	1.000
7:13896065:T:C	Y412C	1.000
7:13896065:T:G	Y412S	1.000
7:13896066:A:C	Y412D	1.000
7:13896066:A:G	Y412H	1.000
7:13896066:A:T	Y412N	1.000
7:13896068:A:T	V411D	1.000
7:13896069:C:A	V411F	1.000
7:13896069:C:G	V411L	1.000
7:13896071:T:C	Y410C	1.000
7:13896071:T:G	Y410S	1.000
7:13896072:A:C	Y410D	1.000
7:13896072:A:G	Y410H	1.000
7:13896072:A:T	Y410N	1.000
7:13896073:T:A	R409S	1.000
7:13896073:T:G	R409S	1.000

dbSNP variants (sampled 300 via entrez): RS1000041552 (7:13928776 G>A,T), RS1000050896 (7:13962364 G>A), RS1000066775 (7:13978112 A>G), RS1000074239 (7:13928560 G>T), RS1000084061 (7:13985050 T>G), RS1000120812 (7:13961067 G>A,C), RS1000136613 (7:13893507 A>G), RS1000150561 (7:13974098 G>C), RS1000188347 (7:13905909 G>A), RS1000239156 (7:13905773 T>C,G), RS1000261682 (7:13932691 G>A), RS1000367876 (7:13990234 A>T), RS1000390252 (7:13913616 T>C), RS1000401148 (7:13989373 G>A,C), RS1000438998 (7:13918408 C>T)

Disease associations

OMIM: gene MIM:600541 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002352_28	Type 2 diabetes	7.000000e-07
GCST002701_12	Verbal declarative memory	3.000000e-06
GCST004627_36	Lymphocyte count	6.000000e-09
GCST005194_62	Coronary artery disease	3.000000e-06
GCST006309_5	Post bronchodilator percent predicted FEV1 in smoking	8.000000e-06
GCST006310_3	Post bronchodilator FEV1/FVC ratio in smoking	3.000000e-06
GCST006988_126	Blond vs. brown/black hair color	2.000000e-11
GCST007576_94	Chronotype	4.000000e-08
GCST007847_97	Type 2 diabetes	3.000000e-09
GCST007998_1	Intraocular pressure	8.000000e-09
GCST008053_80	Height	4.000000e-09
GCST008163_395	Height	2.000000e-06
GCST010118_144	Type 2 diabetes	2.000000e-15
GCST010276_9	Renal underexcretion gout	3.000000e-07
GCST010767_1	Coronary atherosclerosis (time to event)	5.000000e-08
GCST011742_29	Triglyceride levels in HIV infection	9.000000e-06
GCST90002388_19	Lymphocyte count	8.000000e-19
GCST90002400_605	Plateletcrit	2.000000e-12
GCST90002402_13	Platelet count	7.000000e-16
GCST90002407_542	White blood cell count	1.000000e-10
GCST90013662_2	Extrahepatic cholangiocarcinoma	5.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0004587	lymphocyte count
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0003924	hair color
EFO:0008328	chronotype measurement
EFO:0004695	intraocular pressure measurement
EFO:0004918	age at diagnosis
EFO:0007938	coronary atherosclerosis measurement
EFO:0004530	triglyceride measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2010626 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Estradiol	decreases expression, increases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
arsenite	decreases reaction, affects binding	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	increases expression	1
cadmium sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
bicalutamide	decreases reaction, increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	decreases expression	1
entinostat	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dimethylarsinous acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2015224	Binding	Binding affinity to ETV1 by surface plasmon resonance	Unbiased binding assays for discovering small-molecule probes and drugs. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1M8	SEES3-1V human ETV1, clone1	Embryonic stem cell	Male
CVCL_A1M9	SEES3-1V human ETV1, clone2	Embryonic stem cell	Male
CVCL_A1N0	SEES3-1V human ETV1, clone3	Embryonic stem cell	Male
CVCL_AW20	K562 eGFP-ETV1	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.