ETV5

Summary

ETV5 (ETS variant transcription factor 5, HGNC:3494) is a protein-coding gene on chromosome 3q27.2, encoding ETS translocation variant 5 (P41161). Binds to DNA sequences containing the consensus nucleotide core sequence 5’-GGAA.-3'.

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm.

Source: NCBI Gene 2119 — RefSeq curated summary.

At a glance

• GWAS associations: 75
• Clinical variants (ClinVar): 83 total — 1 pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Transcription factor: yes — 23 downstream targets (CollecTRI)
• MANE Select transcript: NM_004454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3494
Approved symbol	ETV5
Name	ETS variant transcription factor 5
Location	3q27.2
Locus type	gene with protein product
Status	Approved
Aliases	ERM
Ensembl gene	ENSG00000244405
Ensembl biotype	protein_coding
OMIM	601600
Entrez	2119

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000306376, ENST00000413301, ENST00000421809, ENST00000422039, ENST00000433149, ENST00000434744, ENST00000440773, ENST00000472868, ENST00000475484, ENST00000476890, ENST00000480706, ENST00000484223, ENST00000489830, ENST00000495808, ENST00000875747, ENST00000875748, ENST00000875749, ENST00000927545, ENST00000927546, ENST00000927547, ENST00000941996

RefSeq mRNA: 1 — MANE Select: NM_004454 NM_004454

CCDS: CCDS33906

Canonical transcript exons

ENST00000306376 — 13 exons

Exon	Start	End
ENSE00001140818	186046314	186048860
ENSE00001151710	186064417	186064476
ENSE00001221695	186079817	186080104
ENSE00001221700	186081046	186081175
ENSE00001333414	186108940	186109089
ENSE00003461842	186105625	186105712
ENSE00003528422	186105449	186105496
ENSE00003541906	186105824	186105942
ENSE00003551638	186057423	186057491
ENSE00003554517	186105305	186105355
ENSE00003586230	186065813	186066072
ENSE00003611845	186057075	186057244
ENSE00003678962	186052030	186052131

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.5272 / max 421.7360, expressed in 1726 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45960	26.4657	1707
45958	2.2371	1073
45959	0.9003	578
45952	0.3299	74
45957	0.3179	163
45955	0.1442	35
45953	0.0596	11
45956	0.0357	9
45951	0.0335	16
45954	0.0033	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.08	gold quality
ventricular zone	UBERON:0003053	96.10	gold quality
secondary oocyte	CL:0000655	94.32	gold quality
adrenal tissue	UBERON:0018303	94.12	gold quality
oocyte	CL:0000023	93.89	gold quality
ganglionic eminence	UBERON:0004023	93.00	gold quality
caput epididymis	UBERON:0004358	91.90	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.29	gold quality
prefrontal cortex	UBERON:0000451	90.33	gold quality
placenta	UBERON:0001987	89.62	gold quality
pituitary gland	UBERON:0000007	89.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.50	gold quality
CA1 field of hippocampus	UBERON:0003881	89.28	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.27	gold quality
adenohypophysis	UBERON:0002196	89.03	gold quality
parietal lobe	UBERON:0001872	88.98	gold quality
postcentral gyrus	UBERON:0002581	88.84	gold quality
superior frontal gyrus	UBERON:0002661	88.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.60	gold quality
adrenal gland	UBERON:0002369	88.45	gold quality
frontal cortex	UBERON:0001870	88.44	gold quality
orbitofrontal cortex	UBERON:0004167	88.23	gold quality
neocortex	UBERON:0001950	88.21	gold quality
right adrenal gland cortex	UBERON:0035827	87.91	gold quality
adrenal cortex	UBERON:0001235	87.74	gold quality
hair follicle	UBERON:0002073	87.72	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	87.59	gold quality
cerebral cortex	UBERON:0000956	87.51	gold quality
cartilage tissue	UBERON:0002418	87.51	gold quality
cingulate cortex	UBERON:0003027	87.47	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

23 targets.

Target	Regulation
CAV1	Unknown
CCL7	Activation
CLDN5	Unknown
CXCL12	Activation
CXCL2	Activation
CXCL5	Activation
CXCR4	Activation
DHRS2	Unknown
ICAM1	Activation
IFNG	Repression
IL10	Activation
IL17A	Activation
IL17F	Repression
IL21	Activation
LTF	Activation
MMP2	Unknown
MUC4	Activation
PARG
PSEN1	Unknown
PTGS2	Unknown
SFTPC	Unknown
SHH
WT1	Activation

JASPAR motifs

Motif	Name	Family
MA0765.1	ETV5	Ets-related
MA0765.2	ETV5	Ets-related
MA0765.3	ETV5	Ets-related
MA0765.4	ETV5	Ets-related
MA1944.1	ETV5::DRGX	Ets-related::Paired-related HD factors
MA1944.2	ETV5::DRGX	Ets-related::Paired-related HD factors
MA1945.1	ETV5::FIGLA	Ets-related::Tal-related
MA1945.2	ETV5::FIGLA	Ets-related::Tal-related
MA1946.1	ETV5::FOXI1	Ets-related::FOX
MA1946.2	ETV5::FOXI1	Ets-related::FOX
MA1947.1	ETV5::FOXO1	Ets-related::FOX
MA1947.2	ETV5::FOXO1	Ets-related::FOX
MA1948.1	ETV5::HOXA2	Ets-related::HOX-related factors
MA1948.2	ETV5::HOXA2	Ets-related::HOX-related factors

JASPAR matrix evidence (PMIDs): PMID:20517297, PMID:25866208, PMID:24218641, PMID:31913281

Upstream regulators (CollecTRI, top): CIC, CTNNB1, DUX4, NFIA, NFIB, NFIX

miRNA regulators (miRDB)

156 targeting ETV5, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754

Literature-anchored findings (GeneRIF, showing 40)

• functional role for the ERMs (ezrin/radixin/moesin) as adaptor molecules in the interactions of adhesion receptors and intracellular tyrosine kinases (PMID:12387735)
• ERM has a role in progression of breast cancer (PMID:15534105)
• The erm gene expression is regulated by the conventional PKC (cPKC) pathway. (PMID:15620692)
• CD44-mediated hyaluronan binding in myeloid cells is regulated by phosphorylated ERM and the actin cytoskeleton. (PMID:15652352)
• ERM is subject to SUMO modification and this post-translational modification causes inhibition of transcription-enhancing activity (PMID:15857832)
• Erm is involved in SP-C regulation, which results from an interaction with TTF-1 (PMID:16613858)
• analysis of NHERF recognition by ERM proteins (PMID:16615918)
• Testing various shorter fragments of ERM as bait indicated that the region essential for binding CHD3/ZFH is within the amino acid region 96-349, which contains the central inhibitory DNA-binding domain (CIDD) of ERM (PMID:17489097)
• ERM/ETV5 up-regulation activates MMP-2 and thus has a role during myometrial infiltration in endometrial cancer (PMID:17638886)
• A TMPRSS2:ETV5 gene fusion was identified in prostate cancer. (PMID:18172298)
• The flexible nature of transactivation domain may be instrumental for ERM recognition and binding to diverse molecular partners. (PMID:20647002)
• results indicate concurrent mechanisms in expression of MMP-2 and -9, RUNX1/AML1 and ETV5/ERM, and several basement membrane components, which likely associate with the invasive stage of endometrioid endometrial and ovarian endometrioid carcinoma. (PMID:20970160)
• Upregulation of ETV5 induced the expression of cell adhesion molecules and enhanced cell survival in a spheroid model. (PMID:21520040)
• Pea3 and Erm, but not Er81, play an important role in the progression of esophageal squamous cell carcinoma (PMID:21689625)
• we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion. (PMID:22266854)
• Review evidence for a role of ETV1, 4 and 5 as oncoproteins and describe modes of their action. (PMID:22425584)
• we found that the downregulation of ETV5 reduced the expression of the oncogenic transcription factor FOXM1. (PMID:22589409)
• The homozygous +48845 G>T (TT allele) variant confers a higher risk for male infertility associated with nonobstructive azoospermia and Sertoli cell only syndrome in Australian men. (PMID:22771031)
• This data suggests that ETV5 has a significant role in regulating MMP2 expression and therefore matrix resorption in human chondrosarcoma, and thus may be a targetable upstream effector of the metastatic cascade in this cancer. (PMID:22968857)
• there is a higher expression of ERM/ETV5 in early stages of endometrioid endometrial carcinomas (PMID:24756106)
• Snail regulates the motility and invasiveness of oral cancer cells via RhoA/Cdc42/p-ERM pathway. (PMID:25172658)
• 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)
• Our results reveal a novel ERM-based spatial mechanism that is coopted by DLBCL cells to sustain tumor cell growth and survival. (PMID:25801911)
• Increase of ETV5 protein expression is associated with endometrial cancer invasion. (PMID:25924802)
• ERM proteins contribute toward accelerated CD44 shedding by MT1-MMP through ERM protein-mediated interactions between their cytoplasmic tails. (PMID:26289026)
• Resistin, a fat-derived secretory factor, promotes metastasis of MDA-MB-231 human breast cancer cells through ERM activation (PMID:26729407)
• MiR-200b inhibition by transfection in MCF-7 markedly decreased miR-200b level, elevated ERM expression, and enhanced cell migration and invasion. MiR-200b overexpression in MDA-MB-231 obviously increased miR-200b level, reduced ERM expression, and weakened cell migration and invasion. (PMID:27276064)
• four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing’s sarcoma breakpoint protein, EWS. (PMID:27783944)
• Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETV1, ETV4 and ETV5. (PMID:28161714)
• the prostate cancer-related oncogenic E26 transformation-specific (ETS) transcription factors, ETV1, ETV4, and ETV5, were required for TAZ gene transcription in PC3 prostate cancer cells (PMID:28408625)
• Novel ETV5 SNP rs7647305 is associated with childhood hypertension adjusted by obesity. (PMID:28645872)
• exploration of the underlying mechanism demonstrated that ICAM3 not only binds to LFA-1 with its extracellular domain and structure protein ERM but also to lamellipodia with its intracellular domain which causes a tension that pulls cells apart (metastasis). (PMID:29729315)
• High Etv5 expression is associated with glioma. (PMID:29787563)
• Study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF-BB. (PMID:30650178)
• ETV5 links the FGFR3 and Hippo signalling pathways in bladder cancer. (PMID:30952872)
• ETS Factor ETV5 Activates the Mutant Telomerase Reverse Transcriptase Promoter in Thyroid Cancer. (PMID:31452441)
• The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness. (PMID:31937834)
• ETV5 enhanced follicular thyroid cancer cell proliferation, migration, and epithelial-mesenchymal transition through the PIK3CA signaling pathway (PMID:32325133)
• ETS variant transcription factor 5 and c-Myc cooperate in derepressing the human telomerase gene promoter via composite ETS/E-box motifs. (PMID:32518154)
• The role of E26 transformation-specific variant transcription factor 5 in colorectal cancer cell proliferation and cell cycle progression. (PMID:33931578)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Etv5	ENSMUSG00000013089
rattus_norvegicus	Etv5	ENSRNOG00000001785

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), ETV4 (ENSG00000175832), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS translocation variant 5 — P41161 (reviewed: P41161)

Alternative names: Ets-related protein ERM

All UniProt accessions (6): C9J0Z2, C9J5A5, C9JMF0, C9JR66, P41161, H7C1D2

UniProt curated annotations — full annotation on UniProt →

Function. Binds to DNA sequences containing the consensus nucleotide core sequence 5’-GGAA.-3'.

Subunit / interactions. Interacts (via C-terminal) with ZMYM5 (via N-terminal 120 amino acid region).

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the ETS family.

Isoforms (2)

UniProt ID	Names	Canonical?
P41161-1	1	yes
P41161-2	2

RefSeq proteins (1): NP_004445* (*=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 (19 total): helix 5, strand 4, compositionally biased region 2, chain 1, DNA-binding region 1, turn 1, region of interest 1, modified residue 1, cross-link 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5ILV	X-RAY DIFFRACTION	1.8
4UNO	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41161-F1	57.46	0.19

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 (2): 248, 350

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 436 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MYAATNNNNNNNGGC_UNKNOWN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_MAMMARY_GLAND_MORPHOGENESIS, FREAC2_01, WWTAAGGC_UNKNOWN, GOBP_GLAND_MORPHOGENESIS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, PAX4_01

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), neuromuscular synaptic transmission (GO:0007274), locomotory behavior (GO:0007626), cell differentiation (GO:0030154), cellular response to oxidative stress (GO:0034599), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), male germ-line stem cell asymmetric division (GO:0048133), regulation of synapse organization (GO:0050807), positive regulation of glial cell proliferation (GO:0060252), regulation of branching involved in mammary gland duct morphogenesis (GO:0060762), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
DNA-templated transcription	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
chemical synaptic transmission	1
behavior	1
cellular developmental process	1
response to oxidative stress	1
cellular response to chemical stress	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of DNA-templated transcription	1
spermatogenesis	1
germline stem cell asymmetric division	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
positive regulation of cell population proliferation	1
glial cell proliferation	1
positive regulation of gliogenesis	1
regulation of glial cell proliferation	1
branching involved in mammary gland duct morphogenesis	1
regulation of morphogenesis of a branching structure	1
regulation of morphogenesis of an epithelium	1
regulation of animal organ morphogenesis	1
postsynaptic membrane organization	1
neuromuscular junction development	1
receptor clustering	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

1656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETV5	DUX4L2	P0CJ85	857
ETV5	SLC45A3	Q96JT2	809
ETV5	GDNF	P39905	784
ETV5	TMPRSS2	O15393	727
ETV5	BCL6B	Q8N143	712
ETV5	GNPDA2	Q8TDQ7	663
ETV5	KCTD15	Q96SI1	657
ETV5	SEC16B	Q96JE7	652
ETV5	ZBTB16	Q05516	649
ETV5	MMP14	P50281	647
ETV5	GFRA1	P56159	627
ETV5	ATXN1L	P0C7T5	625
ETV5	TMEM18	Q96B42	624
ETV5	NEGR1	Q7Z3B1	601
ETV5	MTCH2	Q9Y6C9	584

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ETV5	COP1	psi-mi:“MI:0915”(physical association)	0.600
ETV5	DET1	psi-mi:“MI:0914”(association)	0.530
COP1	ETS2	psi-mi:“MI:0914”(association)	0.460
ETV5	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
LRRK2	ETV5	psi-mi:“MI:0407”(direct interaction)	0.440
AMH	ETV5	psi-mi:“MI:0915”(physical association)	0.370
ETV5	CISH	psi-mi:“MI:0915”(physical association)	0.370
ETV5	CCR5	psi-mi:“MI:0915”(physical association)	0.370
ETV5	CYP3A5	psi-mi:“MI:0915”(physical association)	0.370
HOXD9	ETV5	psi-mi:“MI:0915”(physical association)	0.370
SLC22A2	ETV5	psi-mi:“MI:0915”(physical association)	0.370
ETV5	SEZ6L2	psi-mi:“MI:0915”(physical association)	0.370
ETV5	DHRS7	psi-mi:“MI:0915”(physical association)	0.370
COP1	ACACB	psi-mi:“MI:0914”(association)	0.350
HDAC11	AGPS	psi-mi:“MI:0914”(association)	0.350
COP1	JUN	psi-mi:“MI:0914”(association)	0.350
ETV5	KMT2D	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (51): ETV5 (Affinity Capture-RNA), ETV5 (Affinity Capture-RNA), STK40 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), UBE2E3 (Affinity Capture-MS), DET1 (Affinity Capture-MS), DET1 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), STK40 (Affinity Capture-MS), UBE2E3 (Affinity Capture-MS), ETV5 (Affinity Capture-RNA), ETV5 (Two-hybrid), ETV5 (Reconstituted Complex), ETV5 (Synthetic Lethality)

ESM2 similar proteins: A3RK74, A3RK75, A4L7N3, B3LYS5, B3P0K6, B4HF64, B4MB78, E1BPQ1, F1R8Z9, G3V7R4, O09113, O43524, O93385, P23512, P32183, P35582, P35584, P41161, P55317, P56673, P70314, P78337, P97474, Q00939, Q05826, Q12778, Q28EM1, Q32NP8, Q3BJS1, Q5XKR4, Q60987, Q66JJ0, Q68EZ2, Q68F77, Q6EUW1, Q6EUW2, Q810W5, Q8K3Q3, Q8R5I7, Q969V6

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

6 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	ETV5	phosphorylation
UBE2I	down-regulates	ETV5	sumoylation
SLK	“up-regulates activity”	ETV5	phosphorylation
NFIA	“down-regulates quantity”	ETV5	“transcriptional regulation”
NFIB	“down-regulates quantity”	ETV5	“transcriptional regulation”
NFIX	“down-regulates quantity”	ETV5	“transcriptional regulation”

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	4
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1801782	NM_004454.3(ETV5):c.536A>C (p.His179Pro)	Pathogenic

SpliceAI

2417 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186048641:A:AC	donor_gain	1.0000
3:186048859:ACCTG:A	acceptor_loss	1.0000
3:186048860:CCT:C	acceptor_loss	1.0000
3:186048861:C:CA	acceptor_loss	1.0000
3:186048862:T:G	acceptor_loss	1.0000
3:186052025:CTCA:C	donor_loss	1.0000
3:186052026:TCA:T	donor_loss	1.0000
3:186052027:CA:C	donor_loss	1.0000
3:186052028:ACCT:A	donor_loss	1.0000
3:186052029:C:CG	donor_loss	1.0000
3:186052029:CCTT:C	donor_gain	1.0000
3:186052129:AACC:A	acceptor_loss	1.0000
3:186052130:ACCT:A	acceptor_loss	1.0000
3:186052132:C:CA	acceptor_loss	1.0000
3:186052132:C:CC	acceptor_gain	1.0000
3:186052133:T:C	acceptor_loss	1.0000
3:186057418:CTTA:C	donor_loss	1.0000
3:186057419:TTA:T	donor_loss	1.0000
3:186057420:TA:T	donor_loss	1.0000
3:186057421:A:AC	donor_gain	1.0000
3:186057421:ACC:A	donor_loss	1.0000
3:186057422:C:CC	donor_gain	1.0000
3:186057492:C:CA	acceptor_loss	1.0000
3:186057492:C:CC	acceptor_gain	1.0000
3:186064411:CCTTA:C	donor_loss	1.0000
3:186064412:CTTAC:C	donor_loss	1.0000
3:186064413:TTAC:T	donor_loss	1.0000
3:186064414:TACCT:T	donor_loss	1.0000
3:186064415:A:C	donor_loss	1.0000
3:186064416:C:A	donor_loss	1.0000

AlphaMissense

3336 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186048811:A:G	L454P	1.000
3:186048811:A:T	L454H	1.000
3:186048831:A:C	F447L	1.000
3:186048831:A:T	F447L	1.000
3:186048832:A:C	F447C	1.000
3:186048832:A:G	F447S	1.000
3:186048833:A:C	F447V	1.000
3:186048833:A:G	F447L	1.000
3:186048833:A:T	F447I	1.000
3:186048834:T:A	K446N	1.000
3:186048834:T:G	K446N	1.000
3:186048835:T:A	K446I	1.000
3:186048836:T:C	K446E	1.000
3:186048838:T:C	Y445C	1.000
3:186048838:T:G	Y445S	1.000
3:186048839:A:C	Y445D	1.000
3:186048839:A:G	Y445H	1.000
3:186048839:A:T	Y445N	1.000
3:186048841:A:T	V444D	1.000
3:186048842:C:A	V444F	1.000
3:186048844:T:C	Y443C	1.000
3:186048844:T:G	Y443S	1.000
3:186048845:A:C	Y443D	1.000
3:186048845:A:G	Y443H	1.000
3:186048845:A:T	Y443N	1.000
3:186048847:C:A	R442L	1.000
3:186048847:C:G	R442P	1.000
3:186048847:C:T	R442Q	1.000
3:186048848:G:C	R442G	1.000
3:186048850:T:A	E441V	1.000

dbSNP variants (sampled 300 via entrez): RS1000004413 (3:186104234 G>A), RS1000041095 (3:186059331 G>A), RS1000067721 (3:186066367 T>A), RS1000086505 (3:186071624 C>T), RS1000230910 (3:186080969 G>A,C,T), RS1000338399 (3:186072343 G>A), RS1000369256 (3:186074238 C>T), RS1000403599 (3:186072060 A>G), RS1000415299 (3:186059055 A>C), RS1000455271 (3:186078844 C>T), RS1000463013 (3:186087949 A>G), RS1000504728 (3:186098840 T>C,G), RS1000515186 (3:186110213 AG>A), RS1000605740 (3:186106286 A>G), RS1000648372 (3:186106820 C>T)

Disease associations

OMIM: gene MIM:601600 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

75 associations (top):

Study	Trait	p-value
GCST000296_14	Body mass index	7.000000e-11
GCST000299_16	Weight	4.000000e-09
GCST000830_14	Body mass index	2.000000e-18
GCST000880_42	Menarche (age at onset)	1.000000e-09
GCST001953_32	Obesity	3.000000e-09
GCST001953_47	Obesity	2.000000e-13
GCST001953_53	Obesity	2.000000e-14
GCST001955_9	Body mass index	4.000000e-08
GCST002783_285	Body mass index	1.000000e-24
GCST002783_49	Body mass index	2.000000e-15
GCST002783_542	Body mass index	2.000000e-22
GCST002783_56	Body mass index	1.000000e-12
GCST003401_8	Glomerular filtration rate in non diabetics (creatinine)	1.000000e-09
GCST003993_16	Menarche (age at onset)	6.000000e-07
GCST004065_43	Waist circumference	8.000000e-07
GCST004065_47	Waist circumference	2.000000e-09
GCST004066_1	Hip circumference	3.000000e-07
GCST004066_79	Hip circumference	1.000000e-08
GCST004292_38	Glomerular filtration rate (creatinine)	2.000000e-08
GCST004495_32	BMI (adjusted for smoking behaviour)	2.000000e-11
GCST004495_33	BMI (adjusted for smoking behaviour)	6.000000e-15
GCST004497_127	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-16
GCST004497_128	Body mass index (joint analysis main effects and smoking interaction)	6.000000e-06
GCST004497_132	Body mass index (joint analysis main effects and smoking interaction)	8.000000e-12
GCST004498_7	BMI in smokers	7.000000e-09
GCST004499_28	BMI in non-smokers	1.000000e-08
GCST004499_29	BMI in non-smokers	7.000000e-10
GCST004519_31	Body mass index (adult)	7.000000e-07
GCST004557_129	Body mass index	2.000000e-06
GCST004557_163	Body mass index	3.000000e-17

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0004703	age at menarche
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009104	hyperuricemia
EFO:0004761	uric acid measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004530	triglyceride measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	9
trichostatin A	increases expression, affects cotreatment, decreases expression, affects expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
Estradiol	affects cotreatment, increases expression, decreases expression	4
Doxorubicin	affects expression, increases expression	3
bisphenol A	affects expression, increases methylation	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	2
bisphenol S	affects cotreatment, increases expression, decreases methylation	2
Air Pollutants	increases abundance, increases expression	2
Cadmium	decreases expression, increases abundance	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tunicamycin	decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
Nanotubes, Carbon	increases expression	2
Particulate Matter	increases abundance, increases expression	2
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1

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_A1P0	SEES3-1V human ETV5, clone1	Embryonic stem cell	Male
CVCL_A1P1	SEES3-1V human ETV5, clone2	Embryonic stem cell	Male
CVCL_A1P2	SEES3-1V human ETV5, clone3	Embryonic stem cell	Male
CVCL_B1RM	Abcam HeLa ETV5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis