ERG

Summary

ERG (ETS transcription factor ERG, HGNC:3446) is a protein-coding gene on chromosome 21q22.2, encoding Transcriptional regulator ERG (P11308). Transcriptional regulator.

This gene encodes a member of the erythroblast transformation-specific (ETS) family of transcriptions factors. All members of this family are key regulators of embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis. The protein encoded by this gene is mainly expressed in the nucleus. It contains an ETS DNA-binding domain and a PNT (pointed) domain which is implicated in the self-association of chimeric oncoproteins. This protein is required for platelet adhesion to the subendothelium, inducing vascular cell remodeling. It also regulates hematopoesis, and the differentiation and maturation of megakaryocytic cells. This gene is involved in chromosomal translocations, resulting in different fusion gene products, such as TMPSSR2-ERG and NDRG1-ERG in prostate cancer, EWS-ERG in Ewing’s sarcoma and FUS-ERG in acute myeloid leukemia. More than two dozens of transcript variants generated from combinatorial usage of three alternative promoters and multiple alternative splicing events have been reported, but the full-length nature of many of these variants has not been determined.

Source: NCBI Gene 2078 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myelodysplastic syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 55
• Clinical variants (ClinVar): 71 total — 5 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Transcription factor: yes — 63 downstream targets (CollecTRI)
• MANE Select transcript: NM_182918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3446
Approved symbol	ERG
Name	ETS transcription factor ERG
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	erg-3, p55
Ensembl gene	ENSG00000157554
Ensembl biotype	protein_coding
OMIM	165080
Entrez	2078

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000288319, ENST00000398897, ENST00000398905, ENST00000398907, ENST00000398910, ENST00000398911, ENST00000398919, ENST00000417133, ENST00000442448, ENST00000453032, ENST00000468474, ENST00000473107, ENST00000481609, ENST00000485493, ENST00000492833, ENST00000908854, ENST00000908855, ENST00000908856, ENST00000961235

RefSeq mRNA: 9 — MANE Select: NM_182918 NM_001136154, NM_001136155, NM_001243428, NM_001243429, NM_001243432, NM_001291391, NM_001331025, NM_004449, NM_182918

CCDS: CCDS13657, CCDS13658, CCDS46648, CCDS46649, CCDS58789, CCDS82674

Canonical transcript exons

ENST00000288319 — 10 exons

Exon	Start	End
ENSE00001033342	38390995	38391042
ENSE00001931764	38498363	38498477
ENSE00003462848	38402557	38402637
ENSE00003486142	38400574	38400645
ENSE00003491473	38392376	38392444
ENSE00003508916	38423410	38423561
ENSE00003536380	38403506	38403709
ENSE00003585332	38391659	38391715
ENSE00003712731	38445404	38445621
ENSE00003850376	38380036	38383923

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.91.

FANTOM5 (CAGE): breadth broad, TPM avg 8.4902 / max 370.0355, expressed in 541 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190460	7.4950	393
190459	0.2938	143
190464	0.2709	135
190463	0.1011	37
190462	0.0969	31
190465	0.0763	25
190461	0.0618	15
190458	0.0436	18
190457	0.0384	11
190466	0.0124	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.91	gold quality
descending thoracic aorta	UBERON:0002345	94.69	gold quality
thoracic aorta	UBERON:0001515	93.48	gold quality
ascending aorta	UBERON:0001496	93.40	gold quality
aorta	UBERON:0000947	91.10	gold quality
visceral pleura	UBERON:0002401	89.68	gold quality
tibial artery	UBERON:0007610	89.50	gold quality
popliteal artery	UBERON:0002250	89.48	gold quality
tendon	UBERON:0000043	89.12	gold quality
omental fat pad	UBERON:0010414	89.11	gold quality
peritoneum	UBERON:0002358	89.04	gold quality
sural nerve	UBERON:0015488	89.02	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.58	gold quality
right lung	UBERON:0002167	88.26	gold quality
upper lobe of left lung	UBERON:0008952	87.73	gold quality
upper lobe of lung	UBERON:0008948	87.40	gold quality
adipose tissue	UBERON:0001013	86.90	gold quality
connective tissue	UBERON:0002384	86.74	gold quality
pleura	UBERON:0000977	86.73	gold quality
spleen	UBERON:0002106	86.73	gold quality
calcaneal tendon	UBERON:0003701	86.16	gold quality
right coronary artery	UBERON:0001625	85.88	gold quality
left coronary artery	UBERON:0001626	85.79	gold quality
lung	UBERON:0002048	85.67	gold quality
parietal pleura	UBERON:0002400	85.42	gold quality
gall bladder	UBERON:0002110	85.13	gold quality
metanephros cortex	UBERON:0010533	84.52	gold quality
coronary artery	UBERON:0001621	84.49	gold quality
body of uterus	UBERON:0009853	84.42	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	1196.16
E-CURD-119	yes	34.02
E-HCAD-35	yes	21.87
E-ANND-3	yes	21.72
E-MTAB-8271	yes	14.84
E-MTAB-6678	yes	13.25
E-MTAB-5061	yes	6.44
E-GEOD-130148	yes	4.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

63 targets.

Target	Regulation
ADAMTS1	Activation
AR	Repression
CAT
CCN3
CCNB1	Repression
CDH5	Unknown
CDKN2A
CLDN5	Activation
COL11A2	Unknown
CRISP3	Unknown
CXCL8	Repression
CXCR4	Activation
EGFL7
ENG	Activation
EPB41L3	Repression
EPB41L4B	Activation
ERG	Activation
EZH2	Activation
FGF2	Repression
FZD4	Unknown
GATA2
GATA4
GFI1
H4C13	Unknown
HMOX1	Unknown
HPGD	Unknown
ICAM1	Repression
ICAM2	Unknown
IGF1	Activation
ILK	Repression

JASPAR motifs

Motif	Name	Family
MA0474.2	ERG	Ets-related

JASPAR matrix evidence (PMIDs): PMID:20517297

Upstream regulators (CollecTRI, top): ERG, ESR1, ESR2, ETS1, ETS2, FLI1, GATA3, KDM6A, LMO2, LYL1, MNT, SNAI1, SPI1, TAL1

miRNA regulators (miRDB)

129 targeting ERG, 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-5193	100.00	67.26	1744
HSA-MIR-4673	100.00	66.64	1490
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Literature-anchored findings (GeneRIF, showing 40)

• chemical shift and secondary structure of the PNT/SAM domains (PMID:12449421)
• role in regulating COL11A2 gene transcription (PMID:12554743)
• ERG plays a role in the development of Alzheimer’s disease (AD)-like neuropathology in Down syndrome and in pathogenesis of AD per se; the manifold increase of ERG in both disorders may form a pivotal pathogenetic link. (PMID:15068237)
• Erg and Jun proteins interact in living cells (PMID:15922298)
• The oncogenic TLS-ERG fusion protein activates two different sets of genes sharing little similarity when transforms hematopoietic cells and fibroblasts. (PMID:15988032)
• It is proposed that trisomy 21 facilitates the occurrence of megakaryoblastic leukemias through a shift toward the megakaryoblastic lineage caused by the excess expression of ERG. (PMID:16140924)
• Patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: TLS/ERG. (PMID:16215946)
• High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis in acute myeloid leukemia (PMID:16275934)
• RT-PCR analysis of RNA isolated from bone marrow samples from the patient demonstrates that the translocation occurs within intron 1 of ERG isoform 1 and intron 2 of ELF4 resulting in an in-frame fusion joining exon 2 from ELF4 with exon 2 of ERG. (PMID:16303180)
• Data show the presence of the TMPRSS2/ERG gene fusion is common in prostate adenocarcinoma. (PMID:16575875)
• genomic microdeletion of chromosome 21 is associated with rearrangement, as shown by FISH analysis of TMPRSS2/ERG fusions in prostate cancer (PMID:16820092)
• High expression of ERG is an adverse risk factor in adult T-ALL (PMID:16954520)
• demonstrate for the first time that the TMPRSS2-ERG fusion gene can be detected in a proportion of HGPIN lesions and that this molecular rearrangement is an early event that may precede chromosome-level alterations in prostate carcinogenesis (PMID:17032499)
• ERG overexpression and related ETS transcription factors are important for early prostate carcinogenesis. (PMID:17143509)
• findings show that the TMPRSS2-ERG fusion is common in prostate cancer and that the related TMPRSS2-ETV1 fusion is very rare; frequency of ERG-fusions in the present study is somewhat lower than previously observed (PMID:17390040)
• TMPRSS2:ERG prostate cancer gene fusion may lead to haploinsufficiency or additional fusion events. (PMID:17584912)
• TMPRSS2-ERG fusion protein was found in 35/82 prostate neoplasms. (PMID:17632455)
• Low expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome. (PMID:17646667)
• presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts and indicates consensus sequence may be involved in prostate cancer (PMID:17654723)
• Clonal ERG rearrangements were found both in high grade prostatic intraepithelial neoplasia (PIN) and in atypical in situ epithelial lesions consistent with the diagnosis of low grade PIN. (PMID:17922029)
• Frequent presence of the TMPRSS2-ERG in index tumors suggests critical roles of ERG alterations in the onset and progression of a large subset of prostate cancer. (PMID:18065961)
• a new pathway regulating angiogenesis and endothelial survival, via the transcription factor Erg and the adhesion molecule VE-cadherin. (PMID:18195090)
• Detection of ETS fusion gene by RT-PCR is feasible on formalin-fixed and paraffin-embedded samples. (PMID:18474293)
• TMPRSS2-ERG with interstitial deletion is an aggressive and, in this study, uniformly lethal molecular subtype of prostate cancer associated with androgen-independent disease (PMID:18483239)
• TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel estrogen receptor-dependent mechanism. (PMID:18505969)
• the detection of isolated TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia would improve the positive predictive value of finding TMPRSS2-ERG fusion prostate cancer in subsequent biopsies. (PMID:18519767)
• The TMPRSS2:ERG rearrangement can be found in about one third of prostate cancers. A subgroup of prostate cancer patients with a good prognosis may be identified by the rearrangement. (PMID:18519769)
• IGF1 is a common target gene of Ewing’s sarcoma fusion proteins EWS-FLI-1, EWS-ERG and FUS-ERG in mesenchymal progenitor cells (PMID:18648544)
• analysis of the TMPRSS2-ERG splice variants in prostate cancer (PMID:18676740)
• TMPRSS2-ERG gene fusion has a role in prostate cancer characteristics and outcomes (PMID:18694509)
• TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression. (PMID:18922926)
• TMPRSS2-ERG fusion is frequently observed in Gleason 3 pattern prostate cancer in a Canadian cohort. (PMID:19029822)
• EMA profiling studies on cancer of known ERG status identified a category of cancers associated with markers of poor prognosis (group II) and suggest that factors other than ERG status might be of key importance in determining a poor clinical outcome (PMID:19040532)
• study detected the TMPRSS2-ERG fusion in 44 (59%) familial prostate cancer patients; findings revealed several loci located on chromosomes #9, #18, and X that were suggestive of linkage to the TMPRSS2-ERG fusion-positive prostate cancer phenotype (PMID:19147579)
• The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically (PMID:19151660)
• study discovered three genomic events associated with ERG rearranged prostate cancer, affecting 6q, 7q, and 16q (PMID:19156837)
• Translocation of TMPRSS2-ERG is not associated with outcome and the aggressive clinical features associated with copy number increas in prostate cancer. (PMID:19190343)
• Genetic variation upstream of ERG may alter prostate cancer stage and ultimately prostate cancer-specific death but it is unlikely that it plays a role in prostate cancer development. (PMID:19205910)
• Multicolor fluorescence in situ hybridization shows that CRPC CTCs, metastases, and prostate tissue invariably had the same ERG gene status as therapy-naive tumors. (PMID:19339269)
• Antiinflammatory effects of the ETS factor ERG in endothelial cells are mediated through transcriptional repression of the interleukin-8 gene. (PMID:19359602)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	erg	ENSDARG00000077304
mus_musculus	Erg	ENSMUSG00000040732
rattus_norvegicus	Erg	ENSRNOG00000001652

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), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

Transcriptional regulator ERG — P11308 (reviewed: P11308)

Alternative names: Transforming protein ERG

All UniProt accessions (5): P11308, A0A0C4DG41, A8MX39, A8MZ24, B5MDW0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure.

Subunit / interactions. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with SETDB1.

Subcellular location. Nucleus. Cytoplasm.

Disease relevance. Ewing sarcoma (ES) [MIM:612219] A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ERG has been found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4. Lymphatic malformation 14 (LMPHM14) [MIM:620602] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM14 is an autosomal dominant form. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ETS family.

Isoforms (6)

UniProt ID	Names	Canonical?
P11308-4	1	yes
P11308-3	2, ERG-3
P11308-1	3, ERG-2
P11308-2	4, ERG-1
P11308-5	5
P11308-6	6

RefSeq proteins (9): NP_001129626, NP_001129627, NP_001230357, NP_001230358, NP_001230361, NP_001278320, NP_001317954, NP_004440, NP_891548* (*=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 (40 total): helix 11, splice variant 7, strand 5, turn 4, modified residue 3, region of interest 3, compositionally biased region 2, chain 1, domain 1, cross-link 1, DNA-binding region 1, site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4IRG	X-RAY DIFFRACTION	1.7
4IRH	X-RAY DIFFRACTION	2.1
5YBC	X-RAY DIFFRACTION	2.5
5YBD	X-RAY DIFFRACTION	2.77
4IRI	X-RAY DIFFRACTION	2.77
6VGE	X-RAY DIFFRACTION	4.25
6VGG	X-RAY DIFFRACTION	4.31
1SXE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11308-F1	60.25	0.20

Functional residue map

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

Catalytic / active sites (1): 462–463 (breakpoint for translocation to form elf4-erg oncogene)

Post-translational modifications (4): 81, 96, 282, 48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 285 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, AGGAAGC_MIR5163P, E2F_Q4_01, YAATNRNNNYNATT_UNKNOWN, ACTACCT_MIR196A_MIR196B, FREAC2_01, TAATAAT_MIR126, WWTAAGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, RACCACAR_AML_Q6, HNF1_Q6, FOXO4_01, SP1_Q2_01, NKX61_01

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), sequence-specific double-stranded DNA binding (GO:1990837), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), ribonucleoprotein complex (GO:1990904), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
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
binding	2
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental 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
nucleic acid binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERG	TMPRSS2	O15393	921
ERG	SETDB1	Q15047	782
ERG	SRSF10	O75494	760
ERG	EWSR1	Q01844	751
ERG	AR	P10275	727
ERG	KCNH6	Q9H252	727
ERG	FUS	P35637	675
ERG	KLK3	P07288	570
ERG	SRSF2	Q01130	546
ERG	KCNH2	Q12809	496
ERG	SLC45A3	Q96JT2	453
ERG	PTEN	P60484	430
ERG	SPOP	O43791	420
ERG	NKX3-1	Q99801	404
ERG	CDH5	P33151	384

IntAct

123 interactions, top by confidence:

A	B	Type	Score
XRCC5	PARP1	psi-mi:“MI:0914”(association)	0.880
ERG	AR	psi-mi:“MI:0915”(physical association)	0.690
AR	ERG	psi-mi:“MI:0915”(physical association)	0.690
PRKDC	PARP1	psi-mi:“MI:0914”(association)	0.640
AR	KMT2D	psi-mi:“MI:0914”(association)	0.600
	ERG	psi-mi:“MI:0915”(physical association)	0.560
ERG		psi-mi:“MI:0915”(physical association)	0.560
ERG		psi-mi:“MI:0914”(association)	0.560
	ERG	psi-mi:“MI:0914”(association)	0.560
PARP1	ERG	psi-mi:“MI:0915”(physical association)	0.560
ERG	PARP1	psi-mi:“MI:0914”(association)	0.560
ERG	KDM4A	psi-mi:“MI:0915”(physical association)	0.540
ERG	KDM4A	psi-mi:“MI:0407”(direct interaction)	0.540
PRKDC		psi-mi:“MI:0914”(association)	0.530
NFIA	ERG	psi-mi:“MI:0915”(physical association)	0.470
NFIB	ERG	psi-mi:“MI:0915”(physical association)	0.470
ERG	ERG	psi-mi:“MI:0914”(association)	0.460
ERG	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (322): CUL3 (Affinity Capture-Western), SPOP (Affinity Capture-Western), ERG (Reconstituted Complex), ERG (Affinity Capture-RNA), ERG (Biochemical Activity), ERG (Affinity Capture-Western), SPOP (Affinity Capture-Western), ERG (Biochemical Activity), SPOP (Reconstituted Complex), TRIM25 (Reconstituted Complex), UBR5 (Reconstituted Complex), TRIM33 (Reconstituted Complex), RING1 (Reconstituted Complex), UBR4 (Reconstituted Complex), RNF2 (Reconstituted Complex)

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

38 interactions.

A	Effect	B	Mechanism
ERG	“up-regulates quantity by expression”	MYC	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	EZH2	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	NKX3-1	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	ADAMTS1	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	CXCL8	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	ICAM2	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	VWF	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	ENG	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	ICAM1	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	EPB41L3	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	EPB41L4B	“transcriptional regulation”
GATA3	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
FLI1	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
LMO2	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
LYL1	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
TAL1	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	PIM1	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	SPP1	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	TDRD1	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	VIM	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	WNT11	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	PIM	“transcriptional regulation”
KDM6A	“down-regulates quantity by repression”	ERG	“transcriptional regulation”
RAD21	“down-regulates activity”	ERG	relocalization
ERG	“up-regulates quantity by expression”	CDH5	“transcriptional regulation”
ERG	“up-regulates quantity by expression”	CLDN5	“transcriptional regulation”
GSK3B	“down-regulates quantity by destabilization”	ERG	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Formation of Incision Complex in GG-NER	5	35.2×	1e-04
MITF-M-regulated melanocyte development	5	15.9×	1e-03
DNA Repair	5	13.7×	2e-03
Chromatin organization	5	11.3×	3e-03
Chromatin modifying enzymes	5	10.0×	4e-03
Epigenetic regulation of gene expression	5	9.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	7	6.1×	7e-03

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
204002	GRCh37/hg19 21q22.13-22.2(chr21:38741104..40274106)	Pathogenic
2637893	NM_182918.4(ERG):c.1388del (p.Asn463fs)	Pathogenic
2637894	NM_182918.4(ERG):c.671_672del (p.Thr224fs)	Pathogenic
2637921	NM_182918.4(ERG):c.543del (p.Ser182fs)	Pathogenic
690369	t(21;22)(q21;q12)	Pathogenic

SpliceAI

1890 predictions. Top by Δscore:

Variant	Effect	Δscore
21:38390989:TCTCA:T	donor_loss	1.0000
21:38390990:CTCA:C	donor_loss	1.0000
21:38390991:TCAC:T	donor_loss	1.0000
21:38390992:CA:C	donor_loss	1.0000
21:38390994:C:CA	donor_loss	1.0000
21:38391662:A:C	donor_gain	1.0000
21:38403504:A:AC	donor_gain	1.0000
21:38403505:C:CC	donor_gain	1.0000
21:38403505:CT:C	donor_gain	1.0000
21:38403505:CTCT:C	donor_gain	1.0000
21:38391041:ATCT:A	acceptor_loss	0.9900
21:38391042:TCTA:T	acceptor_loss	0.9900
21:38391043:C:A	acceptor_loss	0.9900
21:38391043:C:CC	acceptor_gain	0.9900
21:38391044:T:G	acceptor_loss	0.9900
21:38391658:CCTAA:C	donor_gain	0.9900
21:38391725:C:CT	acceptor_gain	0.9900
21:38391726:A:T	acceptor_gain	0.9900
21:38392370:CTGTA:C	donor_loss	0.9900
21:38392371:TGTA:T	donor_loss	0.9900
21:38392372:GTA:G	donor_loss	0.9900
21:38392373:TA:T	donor_loss	0.9900
21:38392374:A:G	donor_loss	0.9900
21:38392375:C:G	donor_loss	0.9900
21:38400642:CCCC:C	acceptor_gain	0.9900
21:38400643:CCCC:C	acceptor_gain	0.9900
21:38402638:C:CC	acceptor_gain	0.9900
21:38403508:T:A	donor_gain	0.9900
21:38403552:G:C	donor_gain	0.9900
21:38403709:TCT:T	acceptor_loss	0.9900

AlphaMissense

3164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:38383659:A:C	I395S	1.000
21:38383659:A:T	I395N	1.000
21:38383663:C:A	G394W	1.000
21:38383667:G:C	F392L	1.000
21:38383667:G:T	F392L	1.000
21:38383668:A:C	F392C	1.000
21:38383668:A:G	F392S	1.000
21:38383669:A:G	F392L	1.000
21:38383673:G:C	F390L	1.000
21:38383673:G:T	F390L	1.000
21:38383674:A:C	F390C	1.000
21:38383674:A:G	F390S	1.000
21:38383675:A:C	F390V	1.000
21:38383675:A:G	F390L	1.000
21:38383675:A:T	F390I	1.000
21:38383676:C:A	K389N	1.000
21:38383676:C:G	K389N	1.000
21:38383678:T:C	K389E	1.000
21:38383680:T:C	Y388C	1.000
21:38383681:A:C	Y388D	1.000
21:38383681:A:G	Y388H	1.000
21:38383681:A:T	Y388N	1.000
21:38383683:G:T	A387D	1.000
21:38383684:C:G	A387P	1.000
21:38383686:T:C	Y386C	1.000
21:38383686:T:G	Y386S	1.000
21:38383687:A:C	Y386D	1.000
21:38383687:A:G	Y386H	1.000
21:38383687:A:T	Y386N	1.000
21:38383689:C:A	R385L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007022 (21:38374324 G>A), RS1000008138 (21:38591095 A>G), RS1000012701 (21:38622074 C>G,T), RS1000012972 (21:38644128 A>G), RS1000018318 (21:38549071 C>A,T), RS1000022187 (21:38505279 C>A,T), RS1000050479 (21:38549127 A>C), RS1000059342 (21:38554006 A>AG), RS1000059693 (21:38505487 T>C), RS1000076812 (21:38631630 A>G), RS1000079764 (21:38456099 TTAA>T), RS1000090598 (21:38457167 T>C,G), RS1000121142 (21:38399524 A>G), RS1000128627 (21:38498922 G>A), RS1000134547 (21:38619195 T>C)

Disease associations

OMIM: gene MIM:165080 | disease phenotypes: MIM:614104, MIM:620602, MIM:612219, MIM:162200

GenCC curated gene-disease

Disease	Classification	Inheritance
myelodysplastic syndrome	Strong	Autosomal dominant
lymphatic malformation 14	Limited	Autosomal dominant

Mondo (6): DYRK1A-related intellectual disability syndrome (MONDO:0013578), acute lymphoblastic leukemia (MONDO:0004967), lymphatic malformation 14 (MONDO:0957954), Ewing sarcoma (MONDO:0012817), neurofibromatosis type 1 (MONDO:0018975), myelodysplastic syndrome (MONDO:0018881)

Orphanet (5): DYRK1A-related intellectual disability syndrome (Orphanet:464306), Acute lymphoblastic leukemia (Orphanet:513), OBSOLETE: Neuroepithelioma (Orphanet:2677), Skeletal Ewing sarcoma (Orphanet:319), Neurofibromatosis type 1 (Orphanet:636)

HPO phenotypes

2 total (3 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001004	Lymphedema
HP:0006721	Acute lymphoblastic leukemia

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST000738_1	Neonatal lupus	5.000000e-06
GCST001134_3	White blood cell types	2.000000e-18
GCST001824_13	Metabolite levels (HVA)	3.000000e-06
GCST002337_2	Amyotrophic lateral sclerosis (sporadic)	5.000000e-06
GCST002694_3	General cognitive ability	1.000000e-06
GCST003469_2	Response to cognitive-behavioural therapy in anxiety disorder	6.000000e-06
GCST003566_5	Multiple sclerosis	2.000000e-07
GCST003812_1	Non-response to antidepressants and depression	3.000000e-07
GCST003877_10	Abdominal aortic aneurysm	6.000000e-09
GCST004570_13	Iron status biomarkers (iron levels)	5.000000e-07
GCST004602_239	Mean corpuscular volume	5.000000e-12
GCST004603_145	Platelet count	3.000000e-17
GCST004607_188	Plateletcrit	2.000000e-28
GCST004608_116	Granulocyte percentage of myeloid white cells	3.000000e-09
GCST004609_164	Monocyte percentage of white cells	5.000000e-09
GCST004624_27	Sum eosinophil basophil counts	2.000000e-09
GCST004630_32	Mean corpuscular hemoglobin	1.000000e-09
GCST005976_26	White blood cell count (basophil)	1.000000e-43
GCST006288_412	Heel bone mineral density	8.000000e-08
GCST006288_689	Heel bone mineral density	4.000000e-17
GCST006288_88	Heel bone mineral density	3.000000e-11
GCST006979_182	Heel bone mineral density	1.000000e-42
GCST007094_151	Diastolic blood pressure	1.000000e-06
GCST007096_213	Pulse pressure	2.000000e-09
GCST007268_69	Diastolic blood pressure	2.000000e-08
GCST007269_145	Pulse pressure	2.000000e-10
GCST008870_75	Keratinocyte cancer (MTAG)	4.000000e-11
GCST009597_333	Multiple sclerosis	3.000000e-09
GCST009597_67	Multiple sclerosis	3.000000e-10
GCST009637_1	B-cell acute lymphoblastic leukaemia (high-hyperdiploidy)	5.000000e-09

EFO canonical traits (24, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0005131	HVA measurement
EFO:0004337	intelligence
EFO:0007820	cognitive behavioural therapy
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0004527	mean corpuscular hemoglobin
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0010176	keratinocyte carcinoma
EFO:0004980	appendicular lean mass
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650
D012512	Sarcoma, Ewing	C04.557.450.565.575.650.800; C04.557.450.795.620.800

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293191 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(8R)-8-methyl-3-(4-methyl-1,3-thiazol-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	8 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-8-methyl-3-(2-methyl-1,3-thiazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	16 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-8-methyl-3-(6-methyl-2-pyridinyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-phenylphenyl)methanone	IC50	18 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
6-[(8R)-8-methyl-7-(4-thiophen-2-ylbenzoyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-3-yl]-1H-pyridin-2-one	IC50	18 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-3-(4,5-dimethyl-1,3-thiazol-2-yl)-8-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	21 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-8-methyl-3-(2-methyl-1,3-thiazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-phenylphenyl)methanone	IC50	28 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-8-methyl-3-(2-methyl-1,3-oxazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	34 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
(4-thiophen-2-ylphenyl)-[3-[2-(trifluoromethyl)-1,3-thiazol-4-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	50 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[3-(2-methyl-1,3-thiazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	83 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof

ChEMBL bioactivities

8 potent at pChembl≥5 of 21 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.68	IC50	2100	nM	CHEMBL3234565
5.64	IC50	2300	nM	CHEMBL3234574
5.51	IC50	3100	nM	CHEMBL3234564
5.50	IC50	3200	nM	CHEMBL3234568
5.46	IC50	3500	nM	CHEMBL3234569
5.26	IC50	5500	nM	CHEMBL3234576
5.22	IC50	6000	nM	CHEMBL3234578
5.01	IC50	9800	nM	CHEMBL3234577

PubChem BioAssay actives

8 with measured affinity, of 31 total; 8 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
(3R)-N-[2-(4-cyanophenyl)ethyl]-1-[4-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl]piperidine-3-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	2.1000	uM
(2S)-N-[2-(4-cyanophenyl)ethyl]-1-[6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl]piperidine-2-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	2.3000	uM
(3R)-N-[2-(4-cyanophenyl)ethyl]-1-[4-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]piperidine-3-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	3.1000	uM
(3R)-N-[2-(4-cyanophenyl)ethyl]-1-[6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl]piperidine-3-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	3.2000	uM
(3R)-N-[2-(4-cyanophenyl)ethyl]-1-[6-piperazin-1-yl-2-(trifluoromethyl)pyrimidin-4-yl]piperidine-3-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	3.5000	uM
(2R)-N-[2-(4-cyanophenyl)ethyl]-1-[6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl]pyrrolidine-2-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	5.5000	uM
(2R)-N-[2-(4-cyanophenyl)ethyl]-1-[6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl]azetidine-2-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	6.0000	uM
(2S)-N-[2-(4-cyanophenyl)ethyl]-1-[6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl]azetidine-2-carboxamide	1125920: Inhibition of human ERG by patch clamp method	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
bisphenol A	decreases methylation, increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases reaction, increases expression, affects binding, decreases expression	2
Decitabine	decreases methylation, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bufotalin	decreases expression	1
salinomycin	decreases expression	1
trichostatin A	decreases expression	1
sulforaphane	affects binding, decreases reaction, decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
aflatoxin B2	affects methylation	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Fluvastatin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Androgens	increases mutagenesis, increases reaction	1
Cyclophosphamide	increases expression	1
Endosulfan	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1

ChEMBL screening assays

14 unique, capped per target: 10 binding, 3 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1827530	Binding	Inhibition of human ERG at 10 uM	Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors. — Bioorg Med Chem Lett
CHEMBL1827700	ADMET	Inhibition of human ERG	Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors. — Bioorg Med Chem Lett
CHEMBL2114723	Functional	PubChem BioAssay. qHTS for Small Molecule Inhibitors of the ERG Ets/DNA interaction: HTRF assay against cherry picks. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

39 cell lines: 32 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1103	CADO-ES1	Cancer cell line	Female
CVCL_1216	EW-3	Cancer cell line	Male
CVCL_1576	NCI-H660	Cancer cell line	Male
CVCL_1927	YNH-1	Cancer cell line	Male
CVCL_2235	VCaP	Cancer cell line	Male
CVCL_4Z37	TC-4C	Cancer cell line	Male
CVCL_7123	SCMC-ES1	Cancer cell line	Female
CVCL_7124	SCMC-ES2	Cancer cell line	Male
CVCL_9683	STA-ET-11	Cancer cell line
CVCL_9714	RM-82	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00117507	PHASE4	COMPLETED	Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients
NCT00202371	PHASE4	WITHDRAWN	Transfusion Effects in Myelodysplastic Patients: Limiting Exposure
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00452660	PHASE4	COMPLETED	Evaluation the Effect of Exjade on Oxidative Stress in Low Risk Myelodysplastic Syndrome Patients With Iron Over Load
NCT00481143	PHASE4	COMPLETED	Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndrome and Transfusion-dependent Iron Overload
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488436	PHASE4	COMPLETED	Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
NCT00564941	PHASE4	COMPLETED	Evaluating the Efficacy of Deferasirox in Transfusion Dependent Chronic Anaemias (Myelodysplastic Syndrome, Beta-thalassaemia Patients) With Chronic Iron Overload
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT01011283	PHASE4	TERMINATED	To Demonstrate Superiority of Decitabine Over Azacitidine in Subjects With Intermediate- or High-risk MDS.
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
NCT01201811	PHASE4	COMPLETED	Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
NCT01250951	PHASE4	COMPLETED	This Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT01326845	PHASE4	TERMINATED	Myelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study
NCT01339988	PHASE4	UNKNOWN	Busulfan and Cyclophosphamide Instead of Total Boby Irradiation (TBI) and Cyclophosphamide for Hematological Malignancies Hematocrit (HCT)
NCT02013102	PHASE4	UNKNOWN	A Phase Ⅳ Study of Decitabine in Myelodysplastic Syndrome
NCT02145026	PHASE4	COMPLETED	A Study of Epoetin Beta Treatment in Anemic Participants With Myelodysplastic Syndrome (MDS)
NCT02875743	PHASE4	COMPLETED	King’s Invasive Aspergillosis Study II
NCT03176849	PHASE4	COMPLETED	A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
NCT03335943	PHASE4	UNKNOWN	Myelodysplastic Syndrome–CDA-2 Hematological Improvement National Affirmation Study
NCT03598582	PHASE4	COMPLETED	Biological Predictive Factors of Response to ESA in Low Risk MDS Patients
NCT06004765	PHASE4	UNKNOWN	Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
NCT06006949	PHASE4	UNKNOWN	Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00192673	PHASE4	UNKNOWN	Poly(Ethylene Glycol)(PEG)-Asparaginase During Two Treatment Courses
NCT00222612	PHASE4	UNKNOWN	Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
NCT00411541	PHASE4	COMPLETED	Pulses of Vincristine and Dexamethasone in BFM Protocols for Children With Acute Lymphoblastic Leukemia
NCT00494897	PHASE4	COMPLETED	PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia
NCT00526175	PHASE4	COMPLETED	LAL-BR/2001: Study Treatment to Low Risk ALL
NCT00526305	PHASE4	COMPLETED	LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive
NCT00526409	PHASE4	COMPLETED	LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia
NCT00576472	PHASE4	COMPLETED	Learning Impairments Among Survivors of Childhood Cancer
NCT00797810	PHASE4	UNKNOWN	Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin’s Lymphoma in Adults
NCT00846703	PHASE4	UNKNOWN	The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia
NCT00853008	PHASE4	COMPLETED	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
NCT01358201	PHASE4	UNKNOWN	PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph’ Negative Over 55 Years
NCT01358253	PHASE4	COMPLETED	Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia
NCT01366898	PHASE4	UNKNOWN	Protocol For the Treatment Acute Lymphoblastic Leukemia With Ph ‘Negative in Elderly Patients (> 55 Years)
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study