ETV6

Summary

ETV6 (ETS variant transcription factor 6, HGNC:3495) is a protein-coding gene on chromosome 12p13.2, encoding Transcription factor ETV6 (P41212). Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3’. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma.

Source: NCBI Gene 2120 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia 5 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 911 total — 29 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_001987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3495
Approved symbol	ETV6
Name	ETS variant transcription factor 6
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TEL
Ensembl gene	ENSG00000139083
Ensembl biotype	protein_coding
OMIM	600618
Entrez	2120

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000266427, ENST00000396373, ENST00000541426, ENST00000544715, ENST00000545027, ENST00000904922, ENST00000904923, ENST00000937343, ENST00000937344, ENST00000948724

RefSeq mRNA: 6 — MANE Select: NM_001987 NM_001413913, NM_001413914, NM_001413915, NM_001413916, NM_001413917, NM_001987

CCDS: CCDS8643

Canonical transcript exons

ENST00000396373 — 8 exons

Exon	Start	End
ENSE00001324260	11649674	11650160
ENSE00001623881	11853427	11853561
ENSE00001634229	11839140	11839304
ENSE00001649298	11884445	11884587
ENSE00001657880	11885926	11886026
ENSE00001788162	11869424	11869969
ENSE00002242232	11890941	11895377
ENSE00003678183	11752450	11752579

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 94.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.6425 / max 1008.3741, expressed in 1821 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124245	15.8728	1806
124247	8.3602	1502
124249	1.1224	590
124243	0.9547	346
124246	0.7758	359
124244	0.6655	332
124248	0.5683	267
206626	0.2813	130
124250	0.2682	134
124267	0.2223	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	94.55	gold quality
parotid gland	UBERON:0001831	93.58	gold quality
mammary duct	UBERON:0001765	93.32	gold quality
epithelium of nasopharynx	UBERON:0001951	92.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.98	gold quality
nasal cavity mucosa	UBERON:0001826	92.56	gold quality
saphenous vein	UBERON:0007318	90.89	gold quality
monocyte	CL:0000576	90.83	gold quality
saliva-secreting gland	UBERON:0001044	90.64	gold quality
tibial artery	UBERON:0007610	90.58	gold quality
popliteal artery	UBERON:0002250	90.56	gold quality
mononuclear cell	CL:0000842	90.08	gold quality
minor salivary gland	UBERON:0001830	89.97	gold quality
epithelium of mammary gland	UBERON:0003244	89.89	gold quality
leukocyte	CL:0000738	89.86	gold quality
tonsil	UBERON:0002372	89.45	gold quality
blood	UBERON:0000178	89.41	gold quality
nasal cavity epithelium	UBERON:0005384	88.86	gold quality
aorta	UBERON:0000947	88.58	gold quality
mouth mucosa	UBERON:0003729	88.40	gold quality
skin of leg	UBERON:0001511	88.15	gold quality
colonic epithelium	UBERON:0000397	87.80	gold quality
right coronary artery	UBERON:0001625	86.96	gold quality
mucosa of stomach	UBERON:0001199	86.91	gold quality
visceral pleura	UBERON:0002401	86.42	gold quality
ascending aorta	UBERON:0001496	86.24	gold quality
gingival epithelium	UBERON:0001949	86.20	silver quality
thoracic aorta	UBERON:0001515	86.06	gold quality
zone of skin	UBERON:0000014	85.67	gold quality
left coronary artery	UBERON:0001626	85.53	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	34.04
E-CURD-122	yes	21.80
E-HCAD-25	yes	17.84
E-ANND-3	yes	13.37
E-MTAB-9067	yes	9.71
E-CURD-119	yes	4.39
E-ANND-2	no	1167.88

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ABCB1	Unknown
BBC3	Activation
BCL2L1	Unknown
CCL2	Activation
CCL7	Activation
CDKN1A	Activation
CEL
CR1	Unknown
EPOR	Repression
FAP	Unknown
FLI1	Activation
FPGS	Repression
GAS2	Repression
GP1BA	Repression
HBA1	Activation
HBB	Activation
IGFBP5	Activation
IL10	Activation
IL12B	Repression
IL19	Activation
IL1A	Activation
IL3	Repression
ITGA2B	Repression
MAD2L1	Repression
MMP3	Unknown
PTPN13	Unknown
STAT3
VEGFA	Unknown

JASPAR motifs

Motif	Name	Family
MA0645.1	ETV6	Ets-related
MA0645.2	ETV6	Ets-related

JASPAR matrix evidence (PMIDs): PMID:20400516

Upstream regulators (CollecTRI, top): CREB1, ETV7, KDM6A, RUNX1, STAT3

miRNA regulators (miRDB)

206 targeting ETV6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• We identified a novel ETV6 partner gene, fibroblast growth factor receptor 3 (FGFR3), in a patient with peripheral T-cell lymphoma (PTCL) with a t(4;12)(p16;p13) translocation. (PMID:11731410)
• activates phosphatidylinositol 3 (PI3) kinase and requires PI3 kinase to regulate the cell cycle [TEL/platelet-derived growth factor receptor beta] (PMID:11861293)
• a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13) (PMID:11861295)
• ETV6 functions with ARG as oncofusion protein and triggers the same signaling pathways associated with ABL oncogenes (PMID:12080468)
• the chromosomal translocation leads o formation of TEL/AML1 fusion oncogene and is most common genetic aberration in childhood B-cell precursor ALL. (PMID:12091359)
• TEL-negative PBC-ALL cells expressing a transfected TEL at high levels showed a decreased expression of endogenous TCL1. (PMID:12127395)
• The product of the ETV6-MDS2 fusion transcript in a patient with myelodysplastic syndrome predicts a short ETV6 protein containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking both the PTN and the DNA-binding domains. (PMID:12203785)
• mutational inactivation of ETV6 may occur in prostate carcinoma (PMID:12210491)
• Different clones of t(1;12)/t(12;12) involving the ETV6 gene in a case of acute myeloid leukemia. (PMID:12393285)
• TEL’s functions are potentially regulated by p38 which is activated by various kinds of stresses (PMID:12435397)
• Expression of the ETV6-NTRK3 gene fusion is a primary event in human secretory breast carcinoma. (PMID:12450792)
• Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature. (PMID:12505259)
• Breakpoints in TEL intron 5 and AML1 intron 1 leading to TEL-AML1 fusion is shown to be the initiating step, preceding differentiation to pre-B cells, in childhood acute lymphoblastic leukemia. (PMID:12526921)
• The ability of TEL to repress TEL-responsive promoters is enhanced by the presence of H-L(3)MBT, an effect dependent on the H-L(3)MBT and the TEL interacting domains, which are mapped to their respective SPM/SAM domains. (PMID:12588862)
• the ability of TEL to repress transcription and suppress growth is regulated by sumoylation and nuclear export (PMID:12626745)
• nucleo-cytoplasmic delocalization of the major isoform of TEL-ETV6 is regulated by V-src (PMID:12893822)
• ETV6-NTRK3.IRS-1 complex formation through the NTRK3 C terminus is essential for ETV6-NTRK3 transformation (PMID:14668342)
• TEL-AML1 dramatically alters differentiation of HPCs in vitro, preferentially promoting B-lymphocyte development, enhancing self-renewal of B-cell precursors, and leading to the establishment of long-term growth factor-dependent pre-B-cell lines (PMID:14726384)
• the WW-like domain in the context of TELPDGFbetaR may have both positive and negative regulatory roles in kinase activation. (PMID:15054045)
• we found an incidence of 8.6% of TEL/AML1 translocation in ALL patients (12% of B-lineage ALL) (PMID:15104290)
• TEL-AML1 ALL has significantly lower de novo purine synthesis and differential expression of genes involved in purine metabolism. (PMID:15142881)
• Data show that the repressor activity of TEL/RUNX1 differs from that of TEL, even though both TEL and TEL/RUNX1 interact with the nuclear hormone co-repressor (N-CoR) and histone deacetylase (mSin3A) in vivo. (PMID:15179033)
• Inhibition of Stat3 activity by TEL represents a novel mechanism regulating the Stat3 signaling pathway (PMID:15229229)
• Independent Tel deletion demonstrates a comprehensive analysis of the relationship between diagnostic and relapse clones in childhood ALL. (PMID:15328172)
• Fusion with RUNX1 may provide circumstantial evidence of an increased risk of relapse in leukemia. (PMID:15704129)
• several critical domains within TEL/ARG necessary for function (PMID:15729383)
• Onr third of acute myeloid leukemiea patients have deficient ETV6 protein expression. (PMID:15806161)
• ETV6 rearrangements in invasive breast cancer using fluorescence in situ hybridization (FISH) (PMID:15887243)
• TEL may decide the fate of human erythrocyte/megakaryocyte common progenitors to differentiate towards the erythroid lineage and against the megakaryocytic lineage (PMID:15958056)
• the mechanisms of drug sensitivity and resistance differs between TELAML1-positive ALL and other precursor B-lineage ALL patients. (PMID:15970674)
• meningioma 1-translocation-ETS-leukemia exerts its nonlineage-specific leukemogenic effects by promoting the growth of primitive progenitors and blocking their differentiation (PMID:16081688)
• leukemogenic effect of meningioma 1-TEL in our knock-in mice is pleiotropic, and the type of secondary mutation determines disease outcome (PMID:16105979)
• TEL-AML1 may have a role in T-cell receptor gene rearrangements in pediatric acute lymphoblastic leukemia (PMID:16278392)
• The expression of TEL was found in in 20.3% of children with B-lineage ALL. (PMID:16307024)
• The TCR gene rearrangements in childhood B-lineage acute lymphoblastic leukemia was associated with expression of TEL chimeric oncogene. (PMID:16386788)
• The t(5;12)(q23-31;p13)translocation with ETV6-ACSL6 genomic alteration rearrangement in polycythemia vera patients was reported. (PMID:16572202)
• novel TEL-AML1 fusion in precursor B acute lymphoblastic leukemia (PMID:16673018)
• A nuclear localization signal exists in the C-terminal region of ETV6 within residues 332-452. (PMID:16737910)
• These results suggest that methylation profile may be a potential new biomarker of risk prediction in ETV6/RUNX1-positive acute lymphoblastic leukemias. (PMID:16914570)
• TEL-AML1 fusion in transgenic zebrafish induces a B cell differentiation arrest and demonstrates leukemia development associated with loss of TEL expression and elevated Bcl2/Bax ratio. (PMID:17015828)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Etv6	ENSMUSG00000030199
rattus_norvegicus	Etv6	ENSRNOG00000064991

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), 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

Transcription factor ETV6 — P41212 (reviewed: P41212)

Alternative names: ETS translocation variant 6, ETS-related protein Tel1

All UniProt accessions (4): P41212, A0A0S2Z3C9, H0YG25, J3KN52

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3’. Plays a role in hematopoiesis and malignant transformation.

Subunit / interactions. Can form homodimers or heterodimers with TEL2 or FLI1. Interacts with L3MBTL1 and HDAC9.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylation of Ser-257 by MAPK14 (p38) inhibits ETV6 transcriptional repression.

Disease relevance. A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML). Chromosomal aberrations involving ETV6 are found in acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1. Translocation t(4;12)(q12;p13) with CHIC2. Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. A chromosomal aberration involving ETV6 is found in a form of pre-B acute lymphoid leukemia. Translocation t(9;12)(p24;p13) with JAK2. A chromosomal aberration involving ETV6 and JAK2 is found in an atypical chronic myelogenous leukemia. Translocation t(9;15;12)(p24;q15;p13). A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5. Myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:131440] A hematologic disorder characterized by malignant eosinophils proliferation. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. Leukemia, acute myelogenous (AML) [MIM:601626] A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The gene represented in this entry is involved in disease pathogenesis. Thrombocytopenia 5 (THC5) [MIM:616216] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC5 is an autosomal dominant disorder, associated with an increased susceptibility to the development of hematologic and solid malignancies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ETS family.

RefSeq proteins (6): NP_001400842, NP_001400843, NP_001400844, NP_001400845, NP_001400846, NP_001978* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR003118	Pointed_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178, PF02198

UniProt features (57 total): helix 17, modified residue 8, cross-link 5, strand 5, site 4, sequence variant 4, mutagenesis site 4, turn 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9DOC	X-RAY DIFFRACTION	1.19
9ZB7	X-RAY DIFFRACTION	1.24
9Q4D	X-RAY DIFFRACTION	1.3
7TW9	X-RAY DIFFRACTION	1.41
1JI7	X-RAY DIFFRACTION	1.45
7TDY	X-RAY DIFFRACTION	1.53
7TW8	X-RAY DIFFRACTION	1.55
8FRJ	X-RAY DIFFRACTION	1.57
9DB5	X-RAY DIFFRACTION	1.57
8FT8	X-RAY DIFFRACTION	1.6
8FRK	X-RAY DIFFRACTION	1.61
7TW7	X-RAY DIFFRACTION	1.62
8THA	X-RAY DIFFRACTION	1.68
9ZNB	X-RAY DIFFRACTION	1.77
7JU2	X-RAY DIFFRACTION	1.85
7T8J	X-RAY DIFFRACTION	1.89
8FZU	X-RAY DIFFRACTION	1.9
9ZVU	X-RAY DIFFRACTION	1.96
9FEH	X-RAY DIFFRACTION	1.99
9NGE	X-RAY DIFFRACTION	2.02
9Z2L	X-RAY DIFFRACTION	2.02
7U4Z	X-RAY DIFFRACTION	2.03
9Q9E	X-RAY DIFFRACTION	2.05
7U4W	X-RAY DIFFRACTION	2.1
8E1F	X-RAY DIFFRACTION	2.16
9O0H	X-RAY DIFFRACTION	2.24
1LKY	X-RAY DIFFRACTION	2.3
5L0P	X-RAY DIFFRACTION	2.3
8BWU	X-RAY DIFFRACTION	2.36
2QAR	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41212-F1	62.61	0.21

Functional residue map

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

Catalytic / active sites (4): 336–337 (breakpoint for translocation to form etv6-aml1 in all); 11–12 (breakpoint for translocation to form chic2-etv6 in aml); 54–55 (breakpoint for translocation to form etv6-mds2 in mds); 55–56 (breakpoint for translocation to form pax5-etv6)

Post-translational modifications (13): 11, 18, 22, 213, 238, 257, 302, 323, 11, 288, 302, 403, 421

Mutagenesis-validated functional residues (4):

Position	Phenotype
22	no effect.
213	no effect.
238	no effect.
257	no phosphorylation by mapk14.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9673768	Signaling by membrane-tethered fusions of PDGFRA or PDGFRB
R-HSA-9703465	Signaling by FLT3 fusion proteins

MSigDB gene sets: 329 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GCACCTT_MIR18A_MIR18B, KEGG_DORSO_VENTRAL_AXIS_FORMATION, TATTATA_MIR374, AACYNNNNTTCCS_UNKNOWN, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_2, TTGCWCAAY_CEBPB_02, GOBP_STEM_CELL_PROLIFERATION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, FOSTER_TOLERANT_MACROPHAGE_UP, KORKOLA_EMBRYONAL_CARCINOMA_UP, GATA6_01, GOBP_HEMATOPOIETIC_STEM_CELL_PROLIFERATION

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), vitellogenesis (GO:0007296), neurogenesis (GO:0022008), cell differentiation (GO:0030154), hematopoietic stem cell proliferation (GO:0071425), mesenchymal cell apoptotic process (GO:0097152), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein domain specific binding (GO:0019904), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by PDGFR in disease	1
FLT3 signaling in disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
cytoplasm organization	1
female gamete generation	1
nervous system development	1
cell differentiation	1
cellular developmental process	1
hemopoiesis	1
stem cell proliferation	1
apoptotic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
protein binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETV6	RUNX1	Q01196	982
ETV6	NTRK3	Q16288	972
ETV6	ABL1	P00519	930
ETV6	ABL2	P42684	858
ETV6	PDGFRB	P09619	855
ETV6	CHIC2	Q9UKJ5	852
ETV6	ASXL1	Q8IXJ9	832
ETV6	IKZF1	Q13422	828
ETV6	JAK2	O60674	800
ETV6	PBX1	P40424	796
ETV6	FLT3	P36888	795
ETV6	TET2	Q6N021	785
ETV6	CREBL2	O60519	765
ETV6	NPM1	P06748	750
ETV6	GPR19	Q15760	736

IntAct

70 interactions, top by confidence:

A	B	Type	Score
ETV6	PIN1	psi-mi:“MI:0915”(physical association)	0.740
ETV6	LRP6	psi-mi:“MI:0914”(association)	0.730
ETV7	ETV6	psi-mi:“MI:0914”(association)	0.670
ETV6	LRP5	psi-mi:“MI:0914”(association)	0.640
PIN1	POLR2D	psi-mi:“MI:0914”(association)	0.640
NFE2L2	ETV6	psi-mi:“MI:0915”(physical association)	0.630
ETV6	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
ETV6	AP1M1	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	ETV6	psi-mi:“MI:0915”(physical association)	0.560
AP1M1	ETV6	psi-mi:“MI:0915”(physical association)	0.560
AXIN1	ETV6	psi-mi:“MI:0915”(physical association)	0.560
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
ETV6	HDAC9	psi-mi:“MI:0915”(physical association)	0.520
HDAC9	ETV6	psi-mi:“MI:0915”(physical association)	0.520
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470

BioGRID (147): AP1M1 (Two-hybrid), WDYHV1 (Two-hybrid), LRP6 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), NID2 (Affinity Capture-MS), ETV6 (Affinity Capture-MS), ETV6 (Affinity Capture-MS), ETV6 (Affinity Capture-MS), ETV6 (Affinity Capture-MS), ETV6 (Two-hybrid), ETV6 (Affinity Capture-MS), NID2 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), GAB2 (Affinity Capture-Western)

ESM2 similar proteins: A0JMR6, A1A4L6, A1YG61, A2T737, O70273, O75747, P01105, P10157, P11308, P13474, P14921, P15036, P15037, P15062, P18755, P19102, P26323, P27577, P41156, P41157, P41212, P57782, P81270, P97360, Q08AW4, Q15052, Q32LN0, Q3SZL0, Q3US16, Q58DT0, Q60641, Q6GPJ8, Q6P3D7, Q7ZYI3, Q8BZ05, Q8C7R7, Q8HWS3, Q8N8B7, Q8NDB2, Q8VDK3

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

13 interactions.

A	Effect	B	Mechanism
ETV6	“up-regulates quantity by expression”	HBB	“transcriptional regulation”
ETV6	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
ETV6	up-regulates	Differentiation
KDM6A	“down-regulates quantity by repression”	ETV6	“transcriptional regulation”
PCSK7	down-regulates	ETV6	phosphorylation
MAPK3	down-regulates	ETV6	phosphorylation
ETV6	“up-regulates quantity by expression”	BBC3	“transcriptional regulation”
ETV6	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
ERK1/2	down-regulates	ETV6	phosphorylation
MAPK1	down-regulates	ETV6	phosphorylation
Gbeta	down-regulates	ETV6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
NOTCH1 Intracellular Domain Regulates Transcription	5	23.8×	5e-04
Constitutive Signaling by NOTCH1 PEST Domain Mutants	5	19.7×	5e-04
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	5	19.7×	5e-04
TCF dependent signaling in response to WNT	6	14.1×	5e-04
Signaling by WNT	6	13.4×	5e-04
Diseases of signal transduction by growth factor receptors and second messengers	7	8.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to hypoxia	7	14.1×	4e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — ALL, BLCA, DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	22
Uncertain significance	418
Likely benign	317
Benign	41

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1333000	Single allele	Pathogenic
1338258	NM_001987.5(ETV6):c.1153-1_1165del	Pathogenic
1338390	NM_001987.5(ETV6):c.1153-2_1165del	Pathogenic
162220	NM_001987.5(ETV6):c.1195C>T (p.Arg399Cys)	Pathogenic
190240	NM_001987.4(ETV6):c.1153-5_1153-1del	Pathogenic
2003959	NM_001987.5(ETV6):c.416_417del (p.Ser139fs)	Pathogenic
2694596	NM_001987.5(ETV6):c.1026G>A (p.Trp342Ter)	Pathogenic
2735806	NM_001987.5(ETV6):c.1075C>T (p.Arg359Ter)	Pathogenic
2856371	NM_001987.5(ETV6):c.196_197del (p.Val66fs)	Pathogenic
2857330	NM_001987.5(ETV6):c.452del (p.Asn151fs)	Pathogenic
3061446	NM_001987.5(ETV6):c.921_922del (p.His308fs)	Pathogenic
3064526	NM_001987.5(ETV6):c.1254G>T (p.Arg418Ser)	Pathogenic
3343928	NM_001987.5(ETV6):c.1015A>T (p.Arg339Ter)	Pathogenic
3644474	NM_001987.5(ETV6):c.466_467dup (p.Asn156fs)	Pathogenic
3652385	NM_001987.5(ETV6):c.844del (p.Arg282fs)	Pathogenic
3729142	NM_001987.5(ETV6):c.306_307dup (p.Arg103fs)	Pathogenic
3773668	NM_001987.5(ETV6):c.775dup (p.Arg259fs)	Pathogenic
3846522	NM_001987.5(ETV6):c.963del (p.Val322fs)	Pathogenic
3846537	NM_001987.5(ETV6):c.352C>T (p.Gln118Ter)	Pathogenic
4020044	NM_001987.5(ETV6):c.919_922del (p.Ser307fs)	Pathogenic
4251428	NM_001987.5(ETV6):c.963dup (p.Val322fs)	Pathogenic
4251455	NM_001987.5(ETV6):c.471del (p.Cys157fs)	Pathogenic
4618845	NM_001987.5(ETV6):c.441dup (p.Leu148fs)	Pathogenic
4618855	NM_001987.5(ETV6):c.380_395delinsACT (p.Arg127fs)	Pathogenic
4618856	NM_001987.5(ETV6):c.472_473del (p.Val158fs)	Pathogenic
4826551	NM_001987.5(ETV6):c.613del (p.Leu205fs)	Pathogenic
4842528	NM_001987.5(ETV6):c.613dup (p.Leu205fs)	Pathogenic
8984	NM_001987.5(ETV6):c.226G>T (p.Glu76Ter)	Pathogenic
8985	NM_001987.5(ETV6):c.1307_1308insGGG (p.His436delinsGlnGly)	Pathogenic
1510429	NM_001987.5(ETV6):c.163+1G>A	Likely pathogenic

SpliceAI

2563 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11650081:A:T	donor_gain	1.0000
12:11839138:A:AG	acceptor_gain	1.0000
12:11839139:G:GA	acceptor_loss	1.0000
12:11839139:G:GG	acceptor_gain	1.0000
12:11839302:CAG:C	donor_loss	1.0000
12:11839305:G:A	donor_loss	1.0000
12:11839306:T:A	donor_loss	1.0000
12:11853421:TTCCA:T	acceptor_loss	1.0000
12:11853422:TCCAG:T	acceptor_loss	1.0000
12:11853423:CCAG:C	acceptor_loss	1.0000
12:11853424:CAG:C	acceptor_loss	1.0000
12:11853425:A:AG	acceptor_gain	1.0000
12:11853425:A:T	acceptor_loss	1.0000
12:11853425:AGGT:A	acceptor_gain	1.0000
12:11853426:G:GG	acceptor_gain	1.0000
12:11853426:GGT:G	acceptor_gain	1.0000
12:11853426:GGTG:G	acceptor_gain	1.0000
12:11869966:GCAG:G	donor_gain	1.0000
12:11869968:AG:A	donor_loss	1.0000
12:11869969:GG:G	donor_loss	1.0000
12:11869970:GT:G	donor_loss	1.0000
12:11869971:T:G	donor_loss	1.0000
12:11884441:GTA:G	acceptor_loss	1.0000
12:11884443:A:AC	acceptor_loss	1.0000
12:11884443:A:AG	acceptor_gain	1.0000
12:11884444:G:GA	acceptor_gain	1.0000
12:11884444:GA:G	acceptor_gain	1.0000
12:11884444:GACT:G	acceptor_gain	1.0000
12:11884583:ATAAG:A	donor_loss	1.0000
12:11884584:TAAGG:T	donor_loss	1.0000

AlphaMissense

2990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:11839157:T:A	W61R	1.000
12:11839157:T:C	W61R	1.000
12:11839158:G:C	W61S	1.000
12:11839159:G:C	W61C	1.000
12:11839159:G:T	W61C	1.000
12:11839173:T:A	V66E	1.000
12:11839181:T:A	W69R	1.000
12:11839181:T:C	W69R	1.000
12:11839182:G:C	W69S	1.000
12:11839183:G:C	W69C	1.000
12:11839183:G:T	W69C	1.000
12:11839185:T:C	L70P	1.000
12:11839190:T:A	W72R	1.000
12:11839190:T:C	W72R	1.000
12:11839193:G:C	A73P	1.000
12:11839194:C:A	A73D	1.000
12:11839236:T:C	F87S	1.000
12:11839247:G:C	G91R	1.000
12:11839247:G:T	G91C	1.000
12:11839248:G:A	G91D	1.000
12:11839248:G:T	G91V	1.000
12:11839257:T:A	L94H	1.000
12:11839257:T:C	L94P	1.000
12:11839257:T:G	L94R	1.000
12:11839266:T:C	L97P	1.000
12:11839273:A:C	K99N	1.000
12:11839273:A:T	K99N	1.000
12:11839281:T:C	F102S	1.000
12:11839290:G:C	R105P	1.000
12:11839304:G:C	G110R	1.000

dbSNP variants (sampled 300 via entrez): RS1000007989 (12:11770671 A>T), RS1000038414 (12:11730135 A>G), RS1000050644 (12:11766599 C>T), RS1000076252 (12:11829349 A>G), RS1000076725 (12:11725542 A>G), RS1000085786 (12:11690744 G>A,C), RS1000085870 (12:11666035 C>A,T), RS1000089732 (12:11721583 G>A), RS1000113293 (12:11735575 G>A,T), RS1000119495 (12:11764351 G>C,T), RS1000128695 (12:11823365 C>G), RS1000134494 (12:11783929 T>C), RS1000141185 (12:11853724 G>A), RS1000154537 (12:11891214 A>G), RS1000182143 (12:11728116 C>G,T)

Disease associations

OMIM: gene MIM:600618 | disease phenotypes: MIM:616216, MIM:601626, MIM:203300

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombocytopenia 5	Definitive	Autosomal dominant
acute myeloid leukemia	Strong	Autosomal dominant
hereditary thrombocytopenia and hematologic cancer predisposition syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
thrombocytopenia 5	Definitive	AD

Mondo (9): thrombocytopenia 5 (MONDO:0014536), thrombocytopenia (MONDO:0002049), hereditary neoplastic syndrome (MONDO:0015356), acute myeloid leukemia (MONDO:0018874), acute lymphoblastic leukemia (MONDO:0004967), diffuse large B-cell lymphoma (MONDO:0018905), Hermansky-Pudlak syndrome 1 (MONDO:0008748), chronic myelomonocytic leukemia (MONDO:0020311), hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Orphanet (7): Inherited cancer-predisposing syndrome (Orphanet:140162), Acute myeloid leukemia (Orphanet:519), Acute lymphoblastic leukemia (Orphanet:513), Diffuse large B-cell lymphoma (Orphanet:544), Hermansky-Pudlak syndrome due to BLOC-3 deficiency (Orphanet:231500), Hermansky-Pudlak syndrome (Orphanet:79430), Chronic myelomonocytic leukemia (Orphanet:98823)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000421	Epistaxis
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0001442	Typified by somatic mosaicism
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0004808	Acute myeloid leukemia
HP:0004812	B Acute Lymphoblastic Leukemia
HP:0005518	Increased mean corpuscular volume
HP:0006721	Acute lymphoblastic leukemia

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000175_40	Height	2.000000e-06
GCST000817_99	Height	5.000000e-15
GCST001956_76	Height	3.000000e-11
GCST002647_45	Height	8.000000e-24
GCST003494_3	Colorectal cancer	3.000000e-11
GCST003494_4	Colorectal cancer	3.000000e-10
GCST003542_165	Night sleep phenotypes	6.000000e-06
GCST003831_14	Asthma	4.000000e-06
GCST005981_4	Phosphorus levels	2.000000e-08
GCST007002_5	Cerebrospinal fluid t-tau levels in normal cognition	6.000000e-07
GCST008163_317	Height	2.000000e-11
GCST008839_131	Height	2.000000e-16
GCST010105_131	Nicotine dependence symptom count	5.000000e-06
GCST010105_181	Nicotine dependence symptom count	5.000000e-06
GCST010244_391	Triglyceride levels	2.000000e-10
GCST010989_35	Body size at age 10	1.000000e-14
GCST90000025_1021	Appendicular lean mass	3.000000e-38
GCST90002383_47	Hematocrit	9.000000e-12
GCST90002384_301	Hemoglobin	1.000000e-10
GCST90002390_51	Mean corpuscular hemoglobin	3.000000e-11
GCST90002392_373	Mean corpuscular volume	1.000000e-10
GCST90002396_519	Mean reticulocyte volume	8.000000e-12
GCST90002397_419	Mean spheric corpuscular volume	1.000000e-09
GCST90002403_218	Red blood cell count	1.000000e-12
GCST90011898_9	Alanine aminotransferase levels	8.000000e-13
GCST90013405_5	Liver enzyme levels (alanine transaminase)	4.000000e-19

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004861	phosphorus measurement
EFO:0004760	t-tau measurement
EFO:0009262	nicotine dependence symptom count
EFO:0004530	triglyceride measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D015477	Leukemia, Myelomonocytic, Chronic	C04.557.337.539.522; C15.378.190.615.510; C15.378.508.539.522; C23.550.291.500.495
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C538539	Albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells (supp.)
C563324	Platelet Disorder, Familial, with Associated Myeloid Malignancy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2401606 (SINGLE PROTEIN), CHEMBL3885645 (CHIMERIC PROTEIN), CHEMBL4523666 (CHIMERIC PROTEIN), CHEMBL4630759 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,844 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3545376	ERDAFITINIB	4	2,794
CHEMBL3828009	LY-2874455	1	104

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2724635	ETV6		0.00	0

ChEMBL bioactivities

27 potent at pChembl≥5 of 27 total, top 27 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL4581972
8.37	IC50	4.3	nM	CHEMBL4576727
8.07	IC50	8.5	nM	GILTERITINIB
8.05	IC50	9	nM	LY-2874455
8.02	IC50	9.6	nM	CHEMBL4516515
6.99	IC50	102.5	nM	CHEMBL4529955
6.79	IC50	162	nM	CHEMBL5593851
6.70	IC50	198	nM	CHEMBL5591286
6.67	IC50	213.9	nM	CHEMBL4519811
6.50	IC50	314	nM	CHEMBL5591378
6.49	IC50	323	nM	CHEMBL5594702
6.25	IC50	560	nM	CHEMBL5595996
6.23	IC50	586	nM	CHEMBL5590027
6.20	IC50	627	nM	ERDAFITINIB
6.20	IC50	637	nM	CHEMBL5590821
6.17	IC50	679	nM	CHEMBL5594925
6.06	IC50	864	nM	CHEMBL5594374
6.05	IC50	890	nM	CHEMBL4643578
6.05	IC50	887	nM	CHEMBL5594969
6.00	IC50	990	nM	CHEMBL4644274
5.96	IC50	1100	nM	CHEMBL4639022
5.89	IC50	1300	nM	CHEMBL4636056
5.85	IC50	1400	nM	CHEMBL4640601
5.52	IC50	3000	nM	CHEMBL4642409
5.51	IC50	3100	nM	CHEMBL4638840
5.49	IC50	3250	nM	CERITINIB
5.44	IC50	3600	nM	CHEMBL4640989

PubChem BioAssay actives

28 with measured affinity, of 82 total; 28 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3-cyclopentyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)amino]-6-ethyl-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0003	uM
3-[(3-cyclopropyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)amino]-6-ethyl-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0030	uM
6-ethyl-5-(oxan-4-ylamino)-3-[(7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl)amino]pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0043	uM
Gilteritinib	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0085	uM
2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.0090	uM
6-ethyl-3-[[3-(3-ethylcyclopentyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]amino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0096	uM
3-[[3-(1-aminocyclopropanecarbonyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]amino]-6-ethyl-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.1025	uM
[4-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]piperazin-1-yl]-(4-methylpiperazin-1-yl)methanone	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.1620	uM
5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-3-[6-(4-methylsulfonylpiperazin-1-yl)-3-pyridinyl]-1H-indazole	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.1980	uM
6-ethyl-3-[[3-(1-methylpiperidin-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]amino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.2139	uM
1-[4-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]piperazin-1-yl]propan-1-one	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.3140	uM
4-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]-N,N-dimethylpiperazine-1-carboxamide	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.3230	uM
5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-3-[6-(4-methylsulfonyl-4,7-diazaspiro[2.5]octan-7-yl)-3-pyridinyl]-1H-indazole	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.5600	uM
5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-3-[6-(1-methylsulfonylpiperidin-4-yl)-3-pyridinyl]-1H-indazole	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.5860	uM
Erdafitinib	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.6270	uM
methyl 4-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]piperazine-1-carboxylate	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.6370	uM
1-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]-4-methylsulfonylpiperazin-2-one	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.6790	uM
3-(6-chloro-3-pyridinyl)-5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazole	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.8640	uM
4-[5-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-2-pyridinyl]morpholine	2118393: Inhibition of recombinant TEL/VEGFR2 (unknown origin) transduced in mouse BaF3 cells incubated for 48 hrs by Cell Titer Glo assay	ic50	0.8870	uM
methyl 4-[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]benzoyl]piperazine-1-carboxylate	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	0.8900	uM
3-(3,4-dimethoxyphenyl)-5-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-phenylpyrazolo[1,5-a]pyrimidine-5,7-diamine	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	0.9900	uM
[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]phenyl]-(4-methylsulfonylpiperazin-1-yl)methanone	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	1.1000	uM
[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]phenyl]-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]methanone	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	1.3000	uM
3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxy-6-phenylpyrazolo[1,5-a]pyrimidin-7-amine	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	1.4000	uM
3-(3,4-dimethoxyphenyl)-5-[3-(dimethylamino)propoxy]-6-phenylpyrazolo[1,5-a]pyrimidin-7-amine	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	3.0000	uM
3-(3,4-dimethoxyphenyl)-5-N-(1-methylpiperidin-4-yl)-6-phenylpyrazolo[1,5-a]pyrimidine-5,7-diamine	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	3.1000	uM
Ceritinib	757981: Inhibition of wild-type TEL (unknown origin) by cell-based assay	ic50	3.2500	uM
3-(3,4-dimethoxyphenyl)-6-phenyl-5-piperidin-4-yloxypyrazolo[1,5-a]pyrimidin-7-amine	1648975: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	3.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Cisplatin	decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
Benzo(a)pyrene	increases expression, increases mutagenesis	2
Doxorubicin	decreases expression, increases response to substance	2
Etoposide	increases mutagenesis, increases response to substance	2
Nickel	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
epacadostat	decreases reaction, increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
glycidyl methacrylate	decreases expression	1
methylselenic acid	increases expression	1
trichostatin A	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
indeno(1,2,3-cd)pyrene	decreases reaction, increases expression, increases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2405534	Binding	Inhibition of wild-type TEL (unknown origin) by cell-based assay	Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. — J Med Chem

Cellosaurus cell lines

47 cell lines: 37 cancer cell line, 6 factor-dependent cell line, 3 embryonic stem cell, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0011	KM-3	Cancer cell line	Female
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_1650	Reh	Cancer cell line	Female
CVCL_1807	AP-1060	Cancer cell line	Male
CVCL_2041	FKH-1	Cancer cell line	Male
CVCL_3039	NALL-1	Cancer cell line	Male
CVCL_3943	KOPN-41	Cancer cell line	Male
CVCL_8390	OCUM-9	Cancer cell line	Sex unspecified
CVCL_8462	NOI-90	Cancer cell line	Female
CVCL_8857	EU-1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients