ETV4

Summary

ETV4 (ETS variant transcription factor 4, HGNC:3493) is a protein-coding gene on chromosome 17q21.31, encoding ETS translocation variant 4 (P43268). Transcriptional activator. In precision oncology, ETV4 Overexpression is associated with resistance to Trametinib in Pancreatic Cancer (CIViC Level D); 1 further curated variant–drug associations are listed below.

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in chromosome and nucleolus.

Source: NCBI Gene 2118 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Transcription factor: yes — 69 downstream targets (CollecTRI)
• MANE Select transcript: NM_001079675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3493
Approved symbol	ETV4
Name	ETS variant transcription factor 4
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	E1A-F, E1AF, PEA3
Ensembl gene	ENSG00000175832
Ensembl biotype	protein_coding
OMIM	600711
Entrez	2118

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 3 retained_intron

ENST00000319349, ENST00000393664, ENST00000538265, ENST00000545089, ENST00000545954, ENST00000585508, ENST00000586764, ENST00000586826, ENST00000587151, ENST00000590236, ENST00000591713, ENST00000857843, ENST00000857844, ENST00000922774, ENST00000922775, ENST00000922776, ENST00000922777, ENST00000922778, ENST00000922779, ENST00000922780

RefSeq mRNA: 8 — MANE Select: NM_001079675 NM_001079675, NM_001261437, NM_001261438, NM_001261439, NM_001369366, NM_001369367, NM_001369368, NM_001986

CCDS: CCDS11465, CCDS58553, CCDS59292

Canonical transcript exons

ENST00000319349 — 13 exons

Exon	Start	End
ENSE00001278883	43529504	43529676
ENSE00001278889	43529884	43529952
ENSE00001278900	43530107	43530181
ENSE00001278908	43532674	43532939
ENSE00001279292	43546185	43546340
ENSE00002357228	43529135	43529236
ENSE00002947874	43527846	43528743
ENSE00003471192	43536426	43536479
ENSE00003490351	43533187	43533348
ENSE00003510996	43544975	43545022
ENSE00003594758	43545274	43545367
ENSE00003597089	43545558	43545668
ENSE00003665992	43533859	43533985

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 91.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7964 / max 573.3093, expressed in 1343 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166254	9.8331	1170
166244	2.9157	657
166247	2.4329	667
166249	1.9236	628
166245	0.9662	416
166243	0.8800	372
166250	0.5995	301
166253	0.5951	298
166248	0.4936	254
166251	0.4591	222

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.68	gold quality
type B pancreatic cell	CL:0000169	89.88	gold quality
olfactory bulb	UBERON:0002264	89.69	gold quality
tongue squamous epithelium	UBERON:0006919	89.48	silver quality
lower esophagus mucosa	UBERON:0035834	87.11	gold quality
vena cava	UBERON:0004087	87.06	gold quality
triceps brachii	UBERON:0001509	83.49	gold quality
parotid gland	UBERON:0001831	83.48	gold quality
gluteal muscle	UBERON:0002000	83.18	silver quality
pituitary gland	UBERON:0000007	82.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.71	gold quality
adenohypophysis	UBERON:0002196	82.56	gold quality
cervix squamous epithelium	UBERON:0006922	82.47	gold quality
diaphragm	UBERON:0001103	81.70	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.69	gold quality
nasal cavity epithelium	UBERON:0005384	81.55	gold quality
gingival epithelium	UBERON:0001949	81.53	gold quality
male germ cell	CL:0000015	81.39	gold quality
pharyngeal mucosa	UBERON:0000355	81.22	silver quality
subthalamic nucleus	UBERON:0001906	80.85	gold quality
sperm	CL:0000019	80.40	gold quality
ventral tegmental area	UBERON:0002691	79.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	79.82	gold quality
myocardium	UBERON:0002349	79.69	gold quality
lateral globus pallidus	UBERON:0002476	79.54	gold quality
cardia of stomach	UBERON:0001162	79.50	gold quality
vastus lateralis	UBERON:0001379	79.18	gold quality
left ventricle myocardium	UBERON:0006566	79.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	79.00	gold quality
esophagus mucosa	UBERON:0002469	78.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	95.30
E-ANND-3	yes	3.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

69 targets.

Target	Regulation
ABCB1	Unknown
AGTR1	Activation
BAX	Unknown
BDKRB1	Unknown
CAV1	Unknown
CCL2	Repression
CCND2	Activation
CCND3	Activation
CDKN1A	Activation
CXCL8	Activation
CXCR4	Unknown
DUSP6	Unknown
EGLN1	Unknown
EGR2	Unknown
EP300	Activation
ERBB2	Repression
ETS1	Activation
ETV4	Unknown
FGF10	Unknown
GALT
GBA1	Unknown
GGT1	Unknown
GLI3	Activation
GPX5	Unknown
HPGD	Activation
MEP1B	Unknown
MIR21
MMP1	Unknown
MMP13	Unknown
MMP14	Activation

JASPAR motifs

Motif	Name	Family
MA0764.1	ETV4	Ets-related
MA0764.2	ETV4	Ets-related
MA0764.3	ETV4	Ets-related
MA0764.4	ETV4	Ets-related

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

Upstream regulators (CollecTRI, top): E2F1, ESR1, ETS1, ETV4

miRNA regulators (miRDB)

48 targeting ETV4, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-6880-5P	98.08	65.59	1282

Literature-anchored findings (GeneRIF, showing 40)

• PEA3 has a central role in tumor progression in ovarian carcinoma (PMID:12684413)
• No association of E1AF levels with HER2/neu mRNA levels, hormone receptor status, histological grade, tumor size, lymph node involvement or prognosis was found. (PMID:12779089)
• role in ovarian and breast malignancies and suggests that it may be target for therapeutic intervention (PMID:15387369)
• PEA3, by its capacity to up-regulate the epithelial marker MUC4 and to down-regulate the ErbB-2 oncogene, appears as a key regulator of the differentiation/proliferation balance in pancreatic cancer cells. (PMID:15461591)
• E1AF has an essential role in the activation of the human GalT I gene in highly metastatic lung cancer cells (PMID:15611127)
• E1AF was modified by ubiquitin through the C-terminal region and ubiquitinated E1AF aggregated in nuclear dots, and the inhibition of proteasome-activated transcription from E1AF target promoters (PMID:15629152)
• important role in the early stage of colorectal carcinogenesis (PMID:15695237)
• E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2 into active-MMP-2 (PMID:15756447)
• results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7 (PMID:15800927)
• The ETV4 protein was localised to nuclei of spermatogonia and revealed an intense staining in seminoma cells. (PMID:16158187)
• E1AF is a housekeeping gene, whose expression is controlled in specific tissues. (PMID:16297865)
• Overexpression of ETV4 is identified in 2 of 98 cases of prostate cancer. (PMID:16585160)
• These results provide evidence for the antitumor activity of PEA3 in human breast cancers. (PMID:16652376)
• These data suggest that ETV4 and Myeov may provide novel targets for therapeutic intervention. (PMID:16678123)
• By manipulating LPP levels, we show that it acts to upregulate the transactivation capacity of PEA3. (PMID:16738319)
• PEA3 expression is not correlated with HER-2/neu expression in breast cancer tumor tissues (PMID:16752078)
• PEA3 and c-Jun stimulate synergistically the HER2/neu gene transcription with p300 (PMID:16786139)
• PEA3 stabilization due to LKB1 inactivation could lead to epithelial/mesenchymal transition and greater lung cancer invasion potential. (PMID:16912160)
• Overexpression of PEA3 is associated with breast tumour progression (PMID:17060941)
• E1AF increases cell cycle progression via upregulation of Cyclin D3 transcription, which elicits a new mechanism of breast cancer growth and a new mechanism of Cyclin D3 transcription. (PMID:17467662)
• These results suggest that PEA3 is regulated by EGFR and that the elevated PEA3 expression detected in human ovarian cancer may divert cells to a more invasive phenotype by regulating MMP-9 and MMP-14. (PMID:17475671)
• Our results indicate that PIASy negatively regulates E1AF-mediated transcription by both E1AF sumoylation in a dependent and independent fashion. (PMID:17585876)
• This report describes a new mechanism of glioma invasion involving a cooperative effort between E1AF and Sp1 transcription factors. (PMID:17938207)
• E1AF plays a crucial role in the invasion and metastasis of malignant melanoma through up-regulating the MT1-MMP expression (PMID:18425363)
• The two novel ETV4 fusion partners possess as predominant common characteristics androgen-induction and prostate-specific expression. (PMID:18451133)
• Detection of ETS fusion gene by RT-PCR is feasible on formalin-fixed and paraffin-embedded samples. (PMID:18474293)
• E1AF overexpression markedly enhanced mithramycin A-induced Huh-7 cell apoptosis and the expression of pro-apoptotic protein Bax depending on its DNA-binding domain. (PMID:18510939)
• E1AF is correlated significantly with tumor progression of human rectal cancer and may be an important factor in rectal cancer progression. (PMID:18511876)
• SRC-3/AIB1 directly regulates transcription of matrix metalloproteinase (MMP)-2 and MMP-13 through its coactivation of AP-1 and PEA3. (PMID:18593949)
• In 560 human breast tumors, AIB1 expression was found to be positively associated with PEA3, MMP2, and MMP9. (PMID:18644862)
• activation of E1AF provides a means for E2F1 to induce cell apoptosis in response to DNA damage (PMID:18687701)
• A ubiquitously expressed, androgen-insensitive gene, DDX5, fused in frame with ETV4, leading to the expression of a DDX5-ETV4 fusion protein was identified in prostate cancer. (PMID:18794152)
• Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the VEGF promoter in the cells transfected with PEA3 expression vector (PMID:19129951)
• Sumoylation of PEA3 plays a positive role in PEA3-mediated transcriptional activation and the ERK MAP kinase pathway cooperates with rather than antagonizes this process. (PMID:19307308)
• Increased PEA3 is associated with metastatic lymph node sites in non-small-cell lung cancer. (PMID:19483189)
• Increased expression of E1AF is involved a tumor aggression in prostate neoplasms, a finding that may be influenced by the regulation of MMP-7. (PMID:19845529)
• Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. (PMID:20980337)
• human capicua represses mRNA expression for PEA3 (polyoma enhancer activator 3) Ets transcription factors ETV1, ETV4 and ETV5 (PMID:21087211)
• Study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas. (PMID:21143918)
• study concludes that in breast cancer cells, ERbeta and PEA3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ERbeta and PEA3 - IL-8 pathway (PMID:21266854)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	etv4	ENSDARG00000018303
mus_musculus	Etv4	ENSMUSG00000017724
rattus_norvegicus	Etv4	ENSRNOG00000020792
drosophila_melanogaster	Ets96B	FBGN0039225

Paralogs (28): ETV1 (ENSG00000006468), 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), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS translocation variant 4 — P43268 (reviewed: P43268)

Alternative names: Adenovirus E1A enhancer-binding protein, E1A-F, Polyomavirus enhancer activator 3 homolog

All UniProt accessions (3): P43268, B7Z5F4, K7EMW0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Regulates the positioning of motor neurons within the lateral medial column of the spinal cord and controls the terminal arborization of specific motor neuron axons within their target muscles. Required for the expression of CDH8 and SEMA3E in ETV4-expressing motor neurons and for the exclusion of CDH7 expression from these neurons. May play a role in keratinocyte differentiation. (Microbial infection) Binds to the enhancer of the adenovirus E1A gene and acts as a transcriptional activator; the core-binding sequence is 5’-[AC]GGA[AT]GT-3'.

Subcellular location. Nucleus.

Tissue specificity. Expressed in keratinocytes.

Post-translational modifications. Sumoylated; enhanced upon ERK/MAP kinase pathway activation, it positively regulates the transcriptional activator capacity. Sumoylation at Lys-96 probably requires phosphorylation at Ser-101. Transiently polysumoylated and desumoylated by SENP1. Sumoylation is a prerequisite to polyubiquitination which in turn increases proteasomal-mediated degradation. Probably polyubiquitinated by RNF4 and deubiquitinated by USP2.

Similarity. Belongs to the ETS family.

Isoforms (3)

UniProt ID	Names	Canonical?
P43268-1	1	yes
P43268-2	2
P43268-3	3

RefSeq proteins (8): NP_001073143, NP_001248366, NP_001248367, NP_001248368, NP_001356295, NP_001356296, NP_001356297, NP_001977 (=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 (39 total): mutagenesis site 11, cross-link 6, helix 5, modified residue 4, strand 4, splice variant 2, sequence variant 2, chain 1, DNA-binding region 1, region of interest 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4CO8	X-RAY DIFFRACTION	1.05
5ILU	X-RAY DIFFRACTION	1.1
4UUV	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43268-F1	57.00	0.18

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 (10): 226, 260, 322, 101, 140, 149, 214, 6, 96, 139

Mutagenesis-validated functional residues (11):

Position	Phenotype
96	altered sumoylation pattern. loss of sumoylation, ubiquitination and transcriptional activator function; when associated
98	loss of polysumoylation and ubiquitination; when associated with a-228; a-262; a-324 and a-443.
101	loss of sumoylation at k-96.
101	normal sumoylation at k-96.
102	loss of sumoylation at k-96.
226	altered sumoylation pattern. loss of sumoylation, ubiquitination and transcriptional activator function; when associated
228	loss of polysumoylation and ubiquitination; when associated with a-98; a-262; a-324 and a-443.
260	altered sumoylation pattern. loss of sumoylation, ubiquitination and transcriptional activator function; when associated
262	loss of polysumoylation and ubiquitination; when associated with a-98; a-228; a-324 and a-443.
324	loss of polysumoylation and ubiquitination; when associated with a-98; a-228; a-262 and a-443.
443	loss of polysumoylation and ubiquitination; when associated with a-98; a-228; a-262 and a-324.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5687128	MAPK6/MAPK4 signaling

MSigDB gene sets: 214 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, TGGTGCT_MIR29A_MIR29B_MIR29C, E2F_Q4_01, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, LI_WILMS_TUMOR, CMYB_01, AREB6_01, FOXO4_01, AP2_Q3, USF_C, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), positive regulation of keratinocyte differentiation (GO:0045618), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
nuclear lumen	2
intracellular membraneless organelle	2
cellular developmental process	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETV4	EWSR1	Q01844	819
ETV4	TMPRSS2	O15393	782
ETV4	SLC45A3	Q96JT2	753
ETV4	CD99	P14209	731
ETV4	GDNF	P39905	719
ETV4	EPPIN	O95925	714
ETV4	LPP	Q93052	696
ETV4	SCGB2A2	Q13296	691
ETV4	NCOA3	Q9Y6Q9	637
ETV4	CANT1	Q8WVQ1	626
ETV4	PATZ1	Q9HBE1	622
ETV4	MMP14	P50281	602
ETV4	NCOA1	Q15788	600
ETV4	DUSP6	Q16828	589
ETV4	FUS	P35637	586

IntAct

18 interactions, top by confidence:

A	B	Type	Score
NFE2L2	ETV4	psi-mi:“MI:0915”(physical association)	0.630
ETV4	tax	psi-mi:“MI:0915”(physical association)	0.560
tax	ETV4	psi-mi:“MI:0915”(physical association)	0.560
COP1	ETS2	psi-mi:“MI:0914”(association)	0.460
ETV4	CARM1	psi-mi:“MI:0915”(physical association)	0.400
ETV4	ERF	psi-mi:“MI:0915”(physical association)	0.400
ETV4	HOXD4	psi-mi:“MI:0915”(physical association)	0.370
ATXN1	ETV4	psi-mi:“MI:0915”(physical association)	0.370
HTT	ETV4	psi-mi:“MI:0915”(physical association)	0.370
ETV4	FLOT1	psi-mi:“MI:0914”(association)	0.350
ETV4	BCL9	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (81): STK11 (Affinity Capture-Western), ETV4 (Affinity Capture-Western), ETV4 (Two-hybrid), ETV4 (Biochemical Activity), JUN (Two-hybrid), CARM1 (Affinity Capture-MS), ETV4 (Affinity Capture-RNA), RFWD2 (Affinity Capture-Western), ETV4 (Two-hybrid), HIF1A (FRET), EPAS1 (FRET), ETV4 (Two-hybrid), ETV4 (Two-hybrid), ETV4 (Two-hybrid), ETV4 (Affinity Capture-Western)

ESM2 similar proteins: A0PJS5, A1YG01, A2D4R4, A2D649, A2T6H5, A2T6Z0, A3KNJ3, A7Y7W3, A8K830, F6W2R2, F8VPY8, O15353, O42506, O43186, O54751, P14653, P17919, P28322, P31276, P32243, P40646, P43268, P57082, P70056, P80206, P83758, Q00288, Q06710, Q08820, Q16633, Q1KL10, Q28GC4, Q28IU6, Q2KJA4, Q4G112, Q503Z8, Q64693, Q66IK1, Q66IT9, Q7T1C0

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

3 interactions.

A	Effect	B	Mechanism
ETV4	“up-regulates quantity by expression”	POU5F1	“transcriptional regulation”
ETV4	“up-regulates quantity by expression”	VIM	“transcriptional regulation”
STK11	“down-regulates quantity by destabilization”	ETV4	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — NBL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	3
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

1958 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43528739:GCCAC:G	acceptor_gain	1.0000
17:43528740:CCAC:C	acceptor_gain	1.0000
17:43528740:CCACC:C	acceptor_gain	1.0000
17:43528741:CAC:C	acceptor_gain	1.0000
17:43528741:CACC:C	acceptor_gain	1.0000
17:43528742:AC:A	acceptor_gain	1.0000
17:43528742:ACCTA:A	acceptor_loss	1.0000
17:43528743:CC:C	acceptor_gain	1.0000
17:43528744:C:CC	acceptor_gain	1.0000
17:43528746:A:C	acceptor_gain	1.0000
17:43529182:G:C	donor_gain	1.0000
17:43529505:T:TA	donor_gain	1.0000
17:43529674:CTC:C	acceptor_gain	1.0000
17:43529952:CCT:C	acceptor_gain	1.0000
17:43529954:T:C	acceptor_gain	1.0000
17:43530179:CAT:C	acceptor_gain	1.0000
17:43530180:AT:A	acceptor_gain	1.0000
17:43530181:TC:T	acceptor_loss	1.0000
17:43530182:C:CC	acceptor_gain	1.0000
17:43536417:TCTAC:T	donor_loss	1.0000
17:43536418:CTACT:C	donor_loss	1.0000
17:43536419:TAC:T	donor_loss	1.0000
17:43536420:ACTC:A	donor_loss	1.0000
17:43536421:CT:C	donor_loss	1.0000
17:43536422:TCAC:T	donor_loss	1.0000
17:43536423:CACG:C	donor_loss	1.0000
17:43536424:A:AC	donor_gain	1.0000
17:43536425:C:CC	donor_gain	1.0000
17:43536425:CG:C	donor_gain	1.0000
17:43544971:TCA:T	donor_loss	1.0000

AlphaMissense

3163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:43528714:A:C	F420L	1.000
17:43528714:A:T	F420L	1.000
17:43528715:A:C	F420C	1.000
17:43528715:A:G	F420S	1.000
17:43528716:A:C	F420V	1.000
17:43528716:A:G	F420L	1.000
17:43528716:A:T	F420I	1.000
17:43528722:A:C	Y418D	1.000
17:43528722:A:G	Y418H	1.000
17:43528722:A:T	Y418N	1.000
17:43528727:T:C	Y416C	1.000
17:43528728:A:C	Y416D	1.000
17:43528728:A:G	Y416H	1.000
17:43528731:G:A	R415C	1.000
17:43528731:G:T	R415S	1.000
17:43528736:C:A	G413V	1.000
17:43528736:C:T	G413D	1.000
17:43528737:C:G	G413R	1.000
17:43529135:C:A	K410N	1.000
17:43529135:C:G	K410N	1.000
17:43529136:T:A	K410M	1.000
17:43529137:T:C	K410E	1.000
17:43529137:T:G	K410Q	1.000
17:43529139:T:G	Q409P	1.000
17:43529142:A:C	M408R	1.000
17:43529142:A:G	M408T	1.000
17:43529142:A:T	M408K	1.000
17:43529145:A:C	I407S	1.000
17:43529145:A:G	I407T	1.000
17:43529145:A:T	I407N	1.000

dbSNP variants (sampled 300 via entrez): RS1000120669 (17:43542923 C>A), RS1000169011 (17:43540181 G>T), RS1000198090 (17:43539997 C>A), RS1000352705 (17:43546194 G>A), RS1000475188 (17:43534585 T>C), RS1000580136 (17:43527956 G>A), RS1000741888 (17:43540945 T>C), RS1000986415 (17:43539381 C>A,T), RS1001212469 (17:43533628 T>G), RS1001273887 (17:43530771 A>G), RS1001451141 (17:43547733 A>C), RS1001882311 (17:43536274 G>A), RS1001895727 (17:43541348 C>T), RS1002017036 (17:43542013 C>G,T), RS1002034398 (17:43547772 C>T)

Disease associations

OMIM: gene MIM:600711 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
ETV4 Overexpression	Trametinib	Pancreatic Cancer	Resistance	CIViC D	EID5119
ETV4 Overexpression	Trametinib	Lung Cancer	Resistance	CIViC D	EID5121

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression, decreases activity, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	4
bisphenol A	decreases methylation, affects expression, decreases expression	3
(+)-JQ1 compound	decreases expression, affects cotreatment	3
Estradiol	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Copper	affects cotreatment, decreases expression, affects binding	2
Doxorubicin	decreases expression, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tunicamycin	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
quinomethionate	affects expression	1
hydroxyhydroquinone	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	increases expression	1
sodium arsenite	affects splicing, decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	increases expression	1
cupric chloride	increases expression	1
hydroquinone	increases expression	1
avobenzone	increases expression	1
kahweol	increases expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_A1N7	SEES3-1V human ETV4, clone1	Embryonic stem cell	Male
CVCL_A1N8	SEES3-1V human ETV4, clone2	Embryonic stem cell	Male
CVCL_A1N9	SEES3-1V human ETV4, clone3	Embryonic stem cell	Male
CVCL_D1MG	Abcam K-562 ETV4 KO	Cancer cell line	Female
CVCL_D2J1	Abcam Raji ETV4 KO	Cancer cell line	Male
CVCL_F679	NCR-EW3	Cancer cell line	Male
CVCL_UQ48	Abcam Jurkat ETV4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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