SUZ12

Summary

SUZ12 (SUZ12 polycomb repressive complex 2 subunit, HGNC:17101) is a protein-coding gene on chromosome 17q11.2, encoding Polycomb protein SUZ12 (Q15022). Polycomb group (PcG) protein. It is a selective cancer dependency (DepMap: 35.6% of cell lines).

This zinc finger gene has been identified at the breakpoints of a recurrent chromosomal translocation reported in endometrial stromal sarcoma. Recombination of these breakpoints results in the fusion of this gene and JAZF1. The protein encoded by this gene contains a zinc finger domain in the C terminus of the coding region.

Source: NCBI Gene 23512 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Imagawa-Matsumoto syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 215 total — 16 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 35.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_015355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17101
Approved symbol	SUZ12
Name	SUZ12 polycomb repressive complex 2 subunit
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	JJAZ1, KIAA0160, CHET9
Ensembl gene	ENSG00000178691
Ensembl biotype	protein_coding
OMIM	606245
Entrez	23512

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000322652, ENST00000494429, ENST00000578106, ENST00000580398, ENST00000934317, ENST00000934318, ENST00000934319, ENST00000934320

RefSeq mRNA: 2 — MANE Select: NM_015355 NM_001321207, NM_015355

CCDS: CCDS11270, CCDS82101

Canonical transcript exons

ENST00000322652 — 16 exons

Exon	Start	End
ENSE00000947591	31975482	31975713
ENSE00000947592	31976521	31976614
ENSE00000947593	31982999	31983104
ENSE00000947594	31988320	31988497
ENSE00000947595	31993242	31993333
ENSE00000947596	31993865	31994008
ENSE00001224809	31998658	32001038
ENSE00001327300	31994564	31994721
ENSE00001329515	31937007	31937520
ENSE00002336973	31966147	31966196
ENSE00002349194	31940286	31940332
ENSE00002351833	31940422	31940486
ENSE00002352823	31973146	31973231
ENSE00002420615	31947617	31947685
ENSE00003664776	31995564	31995762
ENSE00003685301	31996798	31996877

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0665 / max 32.2298, expressed in 1545 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160214	2.4725	1306
160215	1.5940	967

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	96.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.17	gold quality
buccal mucosa cell	CL:0002336	94.98	gold quality
choroid plexus epithelium	UBERON:0003911	94.64	gold quality
pylorus	UBERON:0001166	94.44	gold quality
renal medulla	UBERON:0000362	94.39	gold quality
seminal vesicle	UBERON:0000998	93.97	gold quality
hair follicle	UBERON:0002073	93.63	gold quality
cartilage tissue	UBERON:0002418	93.62	gold quality
ventricular zone	UBERON:0003053	93.53	gold quality
corpus epididymis	UBERON:0004359	93.39	gold quality
cauda epididymis	UBERON:0004360	93.23	gold quality
caput epididymis	UBERON:0004358	93.22	gold quality
oral cavity	UBERON:0000167	93.03	gold quality
visceral pleura	UBERON:0002401	93.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.94	gold quality
superficial temporal artery	UBERON:0001614	92.89	gold quality
pigmented layer of retina	UBERON:0001782	92.53	gold quality
superior surface of tongue	UBERON:0007371	92.51	gold quality
bone marrow	UBERON:0002371	92.45	gold quality
placenta	UBERON:0001987	92.44	gold quality
nephron tubule	UBERON:0001231	92.32	gold quality
mammalian vulva	UBERON:0000997	92.30	gold quality
skin of hip	UBERON:0001554	92.23	gold quality
jejunal mucosa	UBERON:0000399	92.18	gold quality
tibia	UBERON:0000979	92.18	gold quality
lower lobe of lung	UBERON:0008949	92.13	gold quality
cardia of stomach	UBERON:0001162	92.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.06	gold quality
esophagus squamous epithelium	UBERON:0006920	91.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.17
E-MTAB-6678	yes	8.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
BANF1
BMI1
CDH1
CEBPD
DAB2IP
DKK1
FOXC1
HBB
HOXA9	Unknown
IGF2	Unknown
KDM6B
PC
PEBP1
ROCK1
SNAI2	Repression
TWIST1	Repression
WNT1

Upstream regulators (CollecTRI, top): E2F1, E2F4

miRNA regulators (miRDB)

191 targeting SUZ12, 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-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
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-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 35.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Endometrial stromal tumors(ESTs) are genetically heterogeneous, with prevalence of JAZF1-JJAZ1 fusion highest among ESTs of classic histology. Diagnostic utility of JAZF1-JJAZ1 fusion transcript assay in ESTs may be limited to classic histologic subset. (PMID:15043312)
• JJAZ1 gene recombination may have a role in mosaicism in neurofibromatosis type 1 (PMID:15257518)
• Data show that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. (PMID:16630818)
• SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A (PMID:16712789)
• The JAZF1-JJAZ1 fusion is a frequent, although nonuniform, feature of endometrial stromal neoplasia. (PMID:17197920)
• SUZ12 regulates H3-K9 methylation in an EZH2-independent fashion. Knockdown of SUZ12 in human cells caused a reduction in H3K27me3 and H3K9me3, and altered the distribution of HP1 alpha. (PMID:17406994)
• The JAFZ1-JJAZ1 fusion gene is present in the endometrial stromal and smooth muscle components of endometrial stromal tumors. (PMID:17667554)
• SUZ12, a component of the polycomb repressor complex 2, is recruited to the beta-globin gene. (PMID:17970752)
• Both benign and malignant forms of endometrial stromal tumor have the JAZF1-JJAZ1 fusion, but only the malignant form also exhibits exclusion of the unrearranged JJAZ1 allele. (PMID:18077430)
• the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo (PMID:18628979)
• YY1 physically interacts with SUZ12 and can act as a mediator to recruit the polycomb group proteins and DNA methyltransferases to participate in the CEBPD gene silencing process (PMID:18753137)
• study shows normal endometrial stromal cells contain a specific chimeric RNA joining 5’ exons of JAZF1 gene on chromosome 7p15 to 3’ exons of JJAZ1/SUZ12 gene on chromosome 17q11; this RNA is translated into JAZF1-JJAZ1 with anti-apoptotic activity (PMID:18772439)
• The JAZF1-JJAZ1 gene fusion was not identified in any Uterine tumor resembling ovarian sex cord tumors (PMID:19542872)
• histone modification including PRC2-mediated repressive histone marker H3K27me3 and active histone marker acH4 may involve in CD11b transcription during HL-60 leukemia cells reprogramming to terminal differentiation[polycomb repressive complex 2 ] (PMID:19578722)
• Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophin. (PMID:19749796)
• SUZ12 blocks cell differentiation, as SUZ12 knockdown releases differentiation programs in a chronic myeloid blastic phase transformed cell line. (PMID:19847889)
• Results support the hypothesis that the abnormal expression of SUZ12 accounts for some of the unexplained features of mantle cell lymphoma, such as abnormal DNA repair and increased resistance to apoptosis. (PMID:20558579)
• findings show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes; A 5’ domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3’ domain of HOTAIR binds the LSD1/CoREST/REST complex (PMID:20616235)
• Loss of miR-200 during CSC formation increases Suz12 expression, Suz12 binding, H3-K27 trimethylation, and Polycomb-mediated repression of the E-cadherin gene. (PMID:20832727)
• We propose Plk1 activity down-regulates ZNF198 and SUZ12, thereby enhancing both HBV replication and pX-mediated oncogenic transformation. (PMID:21480320)
• studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function (PMID:22237151)
• Genetic defects in PRC2 components other than EZH2 are not common in myeloid malignancies. (PMID:22308284)
• SUZ12 promotes the proliferation of human EOC cells by inhibiting apoptosis and HRK is a novel SUZ12 target gene whose upregulation contributes to apoptosis induced by SUZ12 knockdown. (PMID:22964433)
• SUZ12 inactivation results in apoptosis in human colon cancer stem cells. (PMID:23588203)
• Polycomb Repressive Complex 2 overexpression is associated with small cell lung cancer. (PMID:23714854)
• SUZ12 depletion mediated by RNA interference (RNAi) led to a reduction of gastric cell numbers and arrested the cell cycle at G1/S point. (PMID:23735840)
• PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. (PMID:23805300)
• postulate that this interparalog structural difference, together with low allelic recombination rates, could have caused a reduction in NAHGC between SUZ12 and SUZ12P during human evolution (PMID:24385046)
• malat1 promotes bladder cancer metastasis by associating with suz12. (PMID:24449823)
• provide evidences suggesting that SUZ12 is an oncogene in non-small cell lung cancer (PMID:24633887)
• reduction in the total SUZ12 level was not a sufficient cause of the resolution of the epigenetic bivalency of beta-cell transcription factors in embryonic stem cells. (PMID:24845830)
• Data shows EZH2 or SUZ12 depletion leads to HP1 loss from chromatin and degradation. (PMID:25047840)
• the polycomb group gene SUZ12 functions as tumour suppressor in peripheral nerve sheath tumors, high-grade gliomas and melanomas by cooperating with mutations in NF1 (PMID:25119042)
• Polycomb repressive complex 2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. (PMID:25240281)
• found that expression of PcG proteins and H3K27me3 showed prognostic value in our study cohort (PMID:25243792)
• Overexpression of Suz12 was associated with lung adenocarcinoma. (PMID:25279705)
• Somatic mutations of SUZ12 have a central role in malignant transformation of peripheral nerve sheath tumors. (PMID:25305755)
• Data show that overall enhancer of zeste 2 (EZH2), embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12) expression in the colorectal cancer (CRC) tissues was significantly increased than in the non-cancerous tissue. (PMID:25326896)
• Upregulation of SUZ12 was found to play a key role in gastric cancer cell proliferation and metastasis through the regulation of EMT and KLF2 expression (PMID:25672609)
• this study described that miR-489 expression level was significantly reduced in lung cancer samples (n = 115) and cell lines. Abnormal expression of miR-489 regulated the cells invasion by binding SUZ12 3’-UTR in vitro. (PMID:25833694)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	suz12a	ENSDARG00000070256
danio_rerio	suz12b	ENSDARG00000098924
mus_musculus	Suz12	ENSMUSG00000017548
rattus_norvegicus	Suz12	ENSRNOG00000058663
drosophila_melanogaster	Su(z)12	FBGN0020887

Protein

Protein identifiers

Polycomb protein SUZ12 — Q15022 (reviewed: Q15022)

Alternative names: Chromatin precipitated E2F target 9 protein, Joined to JAZF1 protein, Suppressor of zeste 12 protein homolog

All UniProt accessions (2): Q15022, J3QQW9

UniProt curated annotations — full annotation on UniProt →

Function. Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.

Subunit / interactions. Component of the PRC2 complex, which consists of the core subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP. Within the complex, interacts (via C2H2 zinc finger domain) with JARID2 and EPOP; JARID2 and EPOP compete for SUZ12 binding. Also interacts with AEBP2 and PHF19. Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2. Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin. The minimum components required for methyltransferase activity of the PRC2/EZH2 complex are EED, EZH2 and SUZ12. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with WDR77. Interacts with histone H1. Interacts with CDYL. Interacts with BMAL1. Interacts with EZHIP (via C-terminal region). Interacts with ARMC12. Interacts with DDX18; this interaction inhibits the PRC2 complex.

Subcellular location. Nucleus.

Tissue specificity. Overexpressed in breast and colon cancer.

Post-translational modifications. Sumoylated, probably by PIAS2.

Disease relevance. A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. Imagawa-Matsumoto syndrome (IMMAS) [MIM:618786] An autosomal dominant syndrome characterized by generalized overgrowth, dysmorphic features, musculoskeletal abnormalities, developmental delay and intellectual disability. Some patients have genitourinary and structural brain abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Induction. Expression is induced by E2F1, E2F2 and E2F3.

Miscellaneous. Under hypoxic conditions, the precursor SUZ12 RNA undergoes regulated trans-splicing with the JAZF1 RNA, resulting in a chimeric isoform which may be protective against apoptosis. The chimeric transcript is characterized by JAZF1 exons 1-3 joined to SUZ12 exon 2-16. The chimeric transcript is expressed primarily in the endometrium from late secretory and early proliferative phases of the menstrual cycle, but not in normal myometrium at any phase of the cycle. Its expression is slightly induced by low levels of progesterone, but suppressed by both estrogen and high levels of progesterone.

Similarity. Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.

RefSeq proteins (2): NP_001308136, NP_056170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019135	Polycomb_protein_VEFS-Box	Domain
IPR057540	Znf_SUZ12	Domain

Pfam: PF09733, PF23320

UniProt features (81 total): helix 21, strand 21, cross-link 6, region of interest 6, sequence variant 6, mutagenesis site 6, turn 6, modified residue 5, chain 1, zinc finger region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
5IJ7	X-RAY DIFFRACTION	2.62
9XZI	X-RAY DIFFRACTION	2.69
4W2R	X-RAY DIFFRACTION	2.81
6NQ3	X-RAY DIFFRACTION	2.89
5WAI	X-RAY DIFFRACTION	2.9
5HYN	X-RAY DIFFRACTION	2.95
5IJ8	X-RAY DIFFRACTION	2.99
7TD5	X-RAY DIFFRACTION	2.99
6B3W	X-RAY DIFFRACTION	3.05
8VMI	ELECTRON MICROSCOPY	3.1
8VNV	ELECTRON MICROSCOPY	3.1
9C8U	ELECTRON MICROSCOPY	3.1
5WAK	X-RAY DIFFRACTION	3.2
8FYH	ELECTRON MICROSCOPY	3.4
9DCH	ELECTRON MICROSCOPY	3.4
5LS6	X-RAY DIFFRACTION	3.47
6C24	ELECTRON MICROSCOPY	3.5
6WKR	ELECTRON MICROSCOPY	3.5
8VML	ELECTRON MICROSCOPY	3.5
8VNZ	ELECTRON MICROSCOPY	3.5
8EQV	ELECTRON MICROSCOPY	3.64
6C23	ELECTRON MICROSCOPY	3.9
7KSO	ELECTRON MICROSCOPY	3.9
5WG6	X-RAY DIFFRACTION	3.9
8TB9	ELECTRON MICROSCOPY	4
7KSR	ELECTRON MICROSCOPY	4.1
8TAS	ELECTRON MICROSCOPY	4.1
7AT8	ELECTRON MICROSCOPY	4.4
7KTP	ELECTRON MICROSCOPY	4.8
8T9G	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15022-F1	72.78	0.40

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): 93–94 (breakpoint for translocation to form jazf1-suz12 oncogene)

Post-translational modifications (11): 20, 541, 546, 583, 726, 72, 73, 75, 75, 223, 390

Mutagenesis-validated functional residues (6):

Position	Phenotype
86	fails to interact with jarid2; when associated with a-90.
90	fails to interact with jarid2; when associated with a-86.
195–197	fails to form a prc2.1 dimer. reduced h3k27me3 enrichment on prc2 target genes.
196	fails to form a prc2.1 dimer.
334	fails to interact with phf19. the prc2.1 dimer forms but is unstable.
518	no effect on interaction with phf19. the prc2.1 dimer forms but is unstable.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9609690	HCMV Early Events
R-HSA-9710421	Defective pyroptosis
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5619507	Activation of HOX genes during differentiation
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 454 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, GNF2_MCM5, chr17q11, PUJANA_CHEK2_PCC_NETWORK, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GNF2_ANP32B, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, MODULE_206, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell differentiation (GO:0045596), oligodendrocyte differentiation (GO:0048709), random inactivation of X chromosome (GO:0060816), facultative heterochromatin formation (GO:0140718), chromatin organization (GO:0006325)

GO Molecular Function (13): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), transcription corepressor binding (GO:0001222), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), chromatin DNA binding (GO:0031490), histone H3K9me2/3 reader activity (GO:0062072), lncRNA binding (GO:0106222), promoter-specific chromatin binding (GO:1990841), chromatin binding (GO:0003682), RNA binding (GO:0003723), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (10): sex chromatin (GO:0001739), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromatin silencing complex (GO:0005677), nucleolus (GO:0005730), RSC-type complex (GO:0016586), nuclear body (GO:0016604), protein-DNA complex (GO:0032993), ESC/E(Z) complex (GO:0035098), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Cellular Senescence	1
Chromatin modifying enzymes	1
SUMO E3 ligases SUMOylate target proteins	1
Activation of HOX genes during differentiation	1
PTEN Regulation	1
Generic Transcription Pathway	1
HCMV Infection	1
Diseases of programmed cell death	1
Regulation of CDH1 Gene Transcription	1
Regulation of PD-L1(CD274) expression	1
Intracellular signaling by second messengers	1
Gene expression (Transcription)	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	2
chromatin binding	2
binding	2
nuclear lumen	2
intracellular membraneless organelle	2
protein-containing complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
central nervous system development	1
glial cell differentiation	1
dosage compensation by inactivation of X chromosome	1
heterochromatin formation	1
cellular component organization	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription coregulator binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
histone H3 reader activity	1
RNA binding	1
nucleic acid binding	1
cation binding	1
heterochromatin	1
sex chromosome	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
nuclear protein-containing complex	1
SWI/SNF superfamily-type complex	1
nucleoplasm	1

Protein interactions and networks

STRING

3177 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUZ12	EED	O75530	999
SUZ12	EZH2	Q15910	999
SUZ12	RBBP4	P31149	997
SUZ12	RBBP7	Q16576	997
SUZ12	AEBP2	Q6ZN18	997
SUZ12	EZH1	Q92800	997
SUZ12	JARID2	Q92833	997
SUZ12	RNF2	Q99496	995
SUZ12	YY1	P25490	983
SUZ12	MTF2	Q9Y483	983
SUZ12	BMI1	P35226	970
SUZ12	R4GMX3	R4GMX3	970
SUZ12	CBX7	O95931	957
SUZ12	ASXL1	Q8IXJ9	936
SUZ12	JAZF1	Q86VZ6	912
SUZ12	CTCF	P49711	912

IntAct

214 interactions, top by confidence:

A	B	Type	Score
EZH2	SUZ12	psi-mi:“MI:0914”(association)	0.960
SUZ12	EZH2	psi-mi:“MI:0914”(association)	0.960
EZH2	SUZ12	psi-mi:“MI:0915”(physical association)	0.960
SUZ12	EZH2	psi-mi:“MI:2364”(proximity)	0.960
EZH2	EED	psi-mi:“MI:0914”(association)	0.930
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
SUZ12	EED	psi-mi:“MI:0915”(physical association)	0.910
EZH2	PHF1	psi-mi:“MI:0914”(association)	0.900
EED	RBBP4	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
PHF1	EED	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
DNMT3B	EED	psi-mi:“MI:0914”(association)	0.660
DNMT3B	EED	psi-mi:“MI:0403”(colocalization)	0.660
AEBP2	EED	psi-mi:“MI:0915”(physical association)	0.650
AEBP2	EED	psi-mi:“MI:0914”(association)	0.650

BioGRID (958): SUZ12 (Affinity Capture-MS), EZH2 (Affinity Capture-MS), JARID2 (Affinity Capture-MS), EZH1 (Affinity Capture-MS), EED (Affinity Capture-MS), AEBP2 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), SUZ12 (Affinity Capture-MS), SUZ12 (Affinity Capture-Western), JARID2 (Affinity Capture-Western), SUZ12 (Affinity Capture-Western), EZH2 (Affinity Capture-Western), EED (Affinity Capture-Western)

ESM2 similar proteins: A4IFQ0, A6QL63, A6QR06, A7MAZ4, O75486, P54198, Q08BT5, Q0VA03, Q13769, Q14161, Q15022, Q1LVW0, Q28J24, Q3B7L5, Q5BJQ7, Q5RDB9, Q5ZJA9, Q5ZMS1, Q61666, Q62784, Q66H91, Q68FF6, Q68FX7, Q6DEW4, Q6GMF2, Q6GQW0, Q6ZPY2, Q76JQ2, Q7Z7C8, Q7ZYA2, Q80U70, Q8BIK4, Q8BKT7, Q8C0Q9, Q8NFG4, Q8QZS3, Q96BN2, Q96MD2, Q96PE3, Q99LM9

Diamond homologs: B0R1D5, Q0VA03, Q15022, Q6DC03, Q80U70, Q9NJG9, Q8L6Y4, Q8W5B1

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
SUZ12	“form complex”	SUZ12/EED	binding
SUZ12	“form complex”	SUZ12/EZH2	binding
SUZ12	“form complex”	“Polycomb repressive complex 2”	binding
SUZ12	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
SUZ12	“down-regulates quantity by repression”	TWIST1	“transcriptional regulation”
CSNK2A2	“up-regulates activity”	SUZ12	phosphorylation
PLK1	“down-regulates activity”	SUZ12	phosphorylation
PLK1	“down-regulates quantity by destabilization”	SUZ12	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Transcriptional Regulation by E2F6	8	25.7×	1e-07
PRC2 methylates histones and DNA	14	23.4×	4e-13
Regulation of PTEN gene transcription	10	19.6×	2e-08
Negative Regulation of CDH1 Gene Transcription	11	14.5×	5e-08
Defective pyroptosis	8	13.8×	1e-05
Regulation of PD-L1(CD274) transcription	10	11.9×	1e-06
PKMTs methylate histone lysines	6	10.6×	1e-03
Deposition of new CENPA-containing nucleosomes at the centromere	6	10.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription by RNA polymerase III	5	40.7×	1e-05
negative regulation of gene expression, epigenetic	10	34.9×	2e-10
DNA methylation-dependent constitutive heterochromatin formation	6	28.4×	9e-06
protein localization to chromatin	5	25.3×	8e-05
heterochromatin formation	11	24.4×	2e-10
stem cell differentiation	7	18.3×	1e-05
regulation of circadian rhythm	7	15.8×	2e-05
rhythmic process	6	13.1×	3e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — AML, PRAD, SARCNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	11
Uncertain significance	113
Likely benign	33
Benign	8

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1072714	NM_015355.4(SUZ12):c.1891C>T (p.Gln631Ter)	Pathogenic
1075758	NM_015355.4(SUZ12):c.348_349del (p.Tyr117fs)	Pathogenic
1686240	NM_015355.4(SUZ12):c.386+1G>A	Pathogenic
1706550	NM_015355.4(SUZ12):c.156C>G (p.Tyr52Ter)	Pathogenic
3256587	NM_015355.4(SUZ12):c.1828G>C (p.Glu610Gln)	Pathogenic
3363351	NM_015355.4(SUZ12):c.1023+1G>C	Pathogenic
3451510	NM_015355.4(SUZ12):c.588_591del (p.Lys197fs)	Pathogenic
430647	NM_015355.4(SUZ12):c.1829A>T (p.Glu610Val)	Pathogenic
631549	NM_015355.4(SUZ12):c.1794+1G>A	Pathogenic
631551	NM_015355.4(SUZ12):c.1826dup (p.Glu610fs)	Pathogenic
631552	NM_015355.4(SUZ12):c.348_351del (p.Tyr117fs)	Pathogenic
812716	NM_015355.4(SUZ12):c.844_845del (p.Ala282fs)	Pathogenic
812717	NM_015355.4(SUZ12):c.1807T>C (p.Phe603Leu)	Pathogenic
812718	NM_015355.4(SUZ12):c.1960C>T (p.Arg654Ter)	Pathogenic
916088	NM_015355.4(SUZ12):c.1561_1562del (p.Lys521fs)	Pathogenic
976749	NM_015355.4(SUZ12):c.1657C>T (p.Gln553Ter)	Pathogenic
1065437	NM_015355.4(SUZ12):c.1451del (p.Gly484fs)	Likely pathogenic
1308523	NM_015355.4(SUZ12):c.1159C>T (p.Gln387Ter)	Likely pathogenic
1333578	NM_015355.4(SUZ12):c.1437+1G>T	Likely pathogenic
1685459	NM_015355.4(SUZ12):c.1979T>C (p.Leu660Pro)	Likely pathogenic
1705694	NM_015355.4(SUZ12):c.1132dup (p.Ala378fs)	Likely pathogenic
2443323	NM_015355.4(SUZ12):c.1267C>T (p.Arg423Ter)	Likely pathogenic
2506363	NM_015355.4(SUZ12):c.1049C>T (p.Ser350Phe)	Likely pathogenic
3236268	NM_015355.4(SUZ12):c.1603C>T (p.Arg535Ter)	Likely pathogenic
3337642	NM_015355.4(SUZ12):c.586dup (p.Arg196fs)	Likely pathogenic
4685001	NM_015355.4(SUZ12):c.1075_1076del (p.Leu359fs)	Likely pathogenic
4759333	NM_015355.4(SUZ12):c.988A>T (p.Lys330Ter)	Likely pathogenic

SpliceAI

2749 predictions. Top by Δscore:

Variant	Effect	Δscore
17:31937519:GA:G	donor_gain	1.0000
17:31940333:G:GG	donor_gain	1.0000
17:31966142:TTTA:T	acceptor_loss	1.0000
17:31966145:A:AG	acceptor_gain	1.0000
17:31966145:AGCT:A	acceptor_loss	1.0000
17:31966146:G:A	acceptor_loss	1.0000
17:31966146:G:GA	acceptor_gain	1.0000
17:31966146:GCTT:G	acceptor_gain	1.0000
17:31973227:GAAAG:G	donor_gain	1.0000
17:31973228:AAAGG:A	donor_loss	1.0000
17:31973229:AAGG:A	donor_loss	1.0000
17:31973230:AG:A	donor_loss	1.0000
17:31973231:GG:G	donor_loss	1.0000
17:31973233:T:C	donor_loss	1.0000
17:31976519:A:AG	acceptor_gain	1.0000
17:31976520:G:GG	acceptor_gain	1.0000
17:31976520:GAT:G	acceptor_gain	1.0000
17:31988318:A:AG	acceptor_gain	1.0000
17:31988319:G:GG	acceptor_gain	1.0000
17:31988319:GA:G	acceptor_gain	1.0000
17:31993240:A:AG	acceptor_gain	1.0000
17:31993241:G:GA	acceptor_gain	1.0000
17:31993241:GCT:G	acceptor_gain	1.0000
17:31993853:A:AG	acceptor_gain	1.0000
17:31993863:A:AG	acceptor_gain	1.0000
17:31993864:G:GA	acceptor_gain	1.0000
17:31993864:GT:G	acceptor_gain	1.0000
17:31993864:GTTT:G	acceptor_gain	1.0000
17:31994006:GTT:G	donor_gain	1.0000
17:31994551:A:AG	acceptor_gain	1.0000

AlphaMissense

4924 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:31937500:T:C	L85P	1.000
17:31937502:T:A	F86I	1.000
17:31937502:T:C	F86L	1.000
17:31937502:T:G	F86V	1.000
17:31937503:T:C	F86S	1.000
17:31937503:T:G	F86C	1.000
17:31937504:C:A	F86L	1.000
17:31937504:C:G	F86L	1.000
17:31937506:T:A	L87H	1.000
17:31937506:T:C	L87P	1.000
17:31937511:G:C	A89P	1.000
17:31937512:C:A	A89D	1.000
17:31937514:T:A	F90I	1.000
17:31937514:T:C	F90L	1.000
17:31937515:T:C	F90S	1.000
17:31937515:T:G	F90C	1.000
17:31937516:T:A	F90L	1.000
17:31937516:T:G	F90L	1.000
17:31937517:G:A	E91K	1.000
17:31937518:A:T	E91V	1.000
17:31937519:G:C	E91D	1.000
17:31937519:G:T	E91D	1.000
17:31940288:C:T	P93S	1.000
17:31940289:C:A	P93Q	1.000
17:31940289:C:G	P93R	1.000
17:31940289:C:T	P93L	1.000
17:31940292:C:A	T94K	1.000
17:31940292:C:T	T94I	1.000
17:31940295:A:C	Q95P	1.000
17:31940296:G:C	Q95H	1.000

dbSNP variants (sampled 300 via entrez): RS1000055034 (17:31982231 TATA>T), RS1000089657 (17:31959018 AAAAT>A,AAAATAAAT), RS1000276368 (17:31977461 A>G,T), RS1000421702 (17:31999093 T>A,C), RS1000427793 (17:31956973 A>G), RS1000499625 (17:31994076 C>A,G,T), RS1000588526 (17:31987184 G>A,C), RS1000820917 (17:31988827 T>C,G), RS1000844555 (17:31942906 CATT>C), RS1000881561 (17:31978577 G>A), RS1000904187 (17:31973258 G>A,T), RS1000934686 (17:31973453 G>C), RS1000993962 (17:32001146 A>C), RS1001056997 (17:31983536 T>C), RS1001156750 (17:31968574 G>A,T)

Disease associations

OMIM: gene MIM:606245 | disease phenotypes: MIM:236750, MIM:618786, MIM:277590

GenCC curated gene-disease

Disease	Classification	Inheritance
Imagawa-Matsumoto syndrome	Definitive	Autosomal dominant
Weaver syndrome	Supportive	Autosomal dominant

Mondo (6): non-immune hydrops fetalis (MONDO:0009369), Imagawa-Matsumoto syndrome (MONDO:0032916), neurodevelopmental disorder (MONDO:0700092), teratoma (MONDO:0002601), Weaver syndrome (MONDO:0010193), acute megakaryoblastic leukemia in down syndrome (MONDO:0020526)

Orphanet (4): Non-immune hydrops fetalis (Orphanet:363999), Imagawa-Matsumoto syndrome (Orphanet:659463), Weaver syndrome (Orphanet:3447), Acute megakaryoblastic leukemia in children with Down syndrome (Orphanet:99887)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000098	Tall stature
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000336	Prominent supraorbital ridges
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000400	Macrotia
HP:0000494	Downslanted palpebral fissures
HP:0000944	Abnormal metaphysis morphology
HP:0000995	Melanocytic nevus
HP:0000998	Hypertrichosis
HP:0001176	Large hands
HP:0001231	Abnormal fingernail morphology
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001387	Joint stiffness
HP:0001537	Umbilical hernia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004067_135	Hip circumference adjusted for BMI	8.000000e-07
GCST004067_91	Hip circumference adjusted for BMI	3.000000e-10
GCST008954_2	High chromosomal aberration frequency (chromosome type)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0009861	chromosome-type aberration frequency

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D013724	Teratoma	C04.557.465.910
C536687	Weaver syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL2189118 (SINGLE PROTEIN), CHEMBL3137286 (PROTEIN COMPLEX), CHEMBL3137287 (PROTEIN COMPLEX), CHEMBL3301388 (PROTEIN COMPLEX), CHEMBL5169072 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066023 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066550 (PROTEIN COMPLEX), CHEMBL6066551 (PROTEIN COMPLEX), CHEMBL6066587 (PROTEIN COMPLEX), CHEMBL6195577 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,265 (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
CHEMBL3414621	TAZEMETOSTAT	4	1,869
CHEMBL3287735	GSK2816126	1	1,396

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

Binding affinities (BindingDB)

336 measured of 391 human assays (391 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-(2,5-dimethylpyrazol-3-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	0.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(1-oxidopyridin-1-ium-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-4-methyl-2-pyridinyl]-pyrrolidin-1-ylmethanone	IC50	1.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[6-[(dimethylamino)methyl]-2-methyl-3-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-imidazol-1-yl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-ethyl-4-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-6-methylsulfonyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-2-pyridinyl]-pyrrolidin-1-ylmethanone	IC50	1.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(4-chloro-6-methoxy-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(3-methyl-1-propan-2-ylpyrazol-4-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(5-methyl-1-propan-2-ylpyrazol-4-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(6-methoxy-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,5-dimethyl-4-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[2-(fluoromethyl)-3-methyl-4-pyridinyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methyl-6-methylsulfonyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[2-(difluoromethyl)-3-methyl-4-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-ethyl-2-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.7 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(6-methoxy-4-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2-cyclopropyl-4-methylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methylpyrazol-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[3-(difluoromethyl)-1-methylpyrazol-4-yl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,6-dimethyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,4-dimethylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methoxy-4-methylpyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methyl-2-propan-2-yloxypyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
(2R)-1-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-3,5-dimethylpyrazol-1-yl]propan-2-ol	IC50	3.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-fluoro-6-methoxy-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[2-(difluoromethyl)-6-methyl-3-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-cyclopropyl-2-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,3-dimethyl-4-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2-ethoxy-4-methylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methoxypyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
2-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-5-methylpyrazol-1-yl]ethanol	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-N,N,6-trimethylpyridine-2-carboxamide	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(1,5-dimethylpyrazol-4-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[2-(trifluoromethyl)-4-pyridinyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-fluoro-2-methylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methylpyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-4-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.7 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[3-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-2-pyridinyl]methanol	IC50	4.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[4-(1-pyrrolidin-1-ylethyl)phenyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
US10793549, Compound G-63	IC50	5 nM	US-10793549: Sulfuryl-substituted benzoheterocyclic derivative, preparation method and medical use thereof
2-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-3,5-dimethylpyrazol-1-yl]ethanol	IC50	5.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-(2,3-dihydro-1-benzofuran-4-ylmethyl)-8-(2-methylpyrazol-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	5.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-1-methylpyrazol-5-yl]methanol	IC50	6.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[4-[(dimethylamino)methyl]phenyl]-N-[(5-fluoro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	6.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(4-chloro-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	10 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-pyrazol-1-yl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	10 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	10.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof

ChEMBL bioactivities

1726 potent at pChembl≥5 of 1732 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL4159112
9.40	IC50	0.4	nM	CHEMBL4161265
9.30	IC50	0.5	nM	CHEMBL4165937
9.22	Ki	0.6	nM	CHEMBL2204997
9.22	IC50	0.6	nM	CHEMBL4160111
9.22	IC50	0.6	nM	CHEMBL4645324
9.15	IC50	0.7	nM	CHEMBL6016384
9.10	IC50	0.8	nM	CHEMBL4172576
9.05	IC50	0.9	nM	CHEMBL6004759
9.00	IC50	1	nM	CHEMBL5993415
8.92	Ki	1.2	nM	CHEMBL2204995
8.89	IC50	1.3	nM	CHEMBL5933888
8.85	IC50	1.4	nM	CHEMBL6025392
8.85	IC50	1.4	nM	CHEMBL5766995
8.82	IC50	1.5	nM	CHEMBL5795236
8.80	IC50	1.6	nM	CHEMBL5951716
8.77	IC50	1.7	nM	CHEMBL5951716
8.77	IC50	1.7	nM	CHEMBL6031570
8.74	IC50	1.8	nM	CHEMBL4104741
8.72	IC50	1.9	nM	CHEMBL5971900
8.72	IC50	1.9	nM	CHEMBL6053854
8.72	IC50	1.9	nM	CHEMBL5795236
8.70	IC50	2	nM	CHEMBL5840875
8.70	IC50	2	nM	CHEMBL5904947
8.70	IC50	2	nM	CHEMBL4633469
8.70	IC50	2	nM	CHEMBL5820899
8.68	IC50	2.1	nM	CHEMBL5789398
8.68	IC50	2.1	nM	CHEMBL5785816
8.67	IC50	2.15	nM	CHEMBL6052145
8.66	IC50	2.2	nM	CHEMBL5770540
8.66	IC50	2.2	nM	CHEMBL5795236
8.66	IC50	2.2	nM	CHEMBL5830594
8.64	IC50	2.3	nM	CHEMBL5825196
8.64	IC50	2.3	nM	CHEMBL5810047
8.64	IC50	2.3	nM	CHEMBL5792222
8.62	IC50	2.4	nM	CHEMBL5747283
8.62	IC50	2.4	nM	CHEMBL5881122
8.62	IC50	2.4	nM	CHEMBL5950883
8.62	IC50	2.4	nM	CHEMBL5944906
8.62	IC50	2.4	nM	CHEMBL5917845
8.62	IC50	2.4	nM	CHEMBL5972032
8.60	IC50	2.5	nM	CHEMBL5943120
8.60	IC50	2.5	nM	CHEMBL5785469
8.60	IC50	2.5	nM	CHEMBL5919510
8.60	IC50	2.5	nM	CHEMBL5755546
8.59	IC50	2.6	nM	CHEMBL4755618
8.59	IC50	2.6	nM	CHEMBL5926210
8.59	IC50	2.6	nM	CHEMBL5877145
8.59	IC50	2.6	nM	CHEMBL5927708
8.58	IC50	2.65	nM	CHEMBL6024531

PubChem BioAssay actives

54 with measured affinity, of 85 total; 41 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
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0001	uM
2-chloro-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0004	uM
2-cyclopropyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0005	uM
N-[(4-ethyl-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0006	uM
N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0006	uM
2-cyano-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0008	uM
N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0012	uM
(3R,4S)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethyl-4-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]pyrrolidin-3-amine	1925352: Inhibition of EZH2-EED-SUZ12 (unknown origin) complex assessed as nucleosome methylation by radioactivity based assay	ic50	0.0018	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-2-(trifluoromethyl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0027	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2,5-dimethyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0029	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0033	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-2,5-dimethyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0038	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(1-propan-2-ylpiperidin-4-yl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0040	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0040	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0040	uM
Tazemetostat	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0040	uM
6-[ethyl(oxan-4-yl)amino]-2-fluoro-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0041	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(morpholin-4-ylmethyl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0046	uM
6-[ethyl(oxan-4-yl)amino]-5-methyl-N-[[6-methyl-2-oxo-4-(trifluoromethyl)-1H-pyridin-3-yl]methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0046	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-3,5-dimethyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0059	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-5-methyl-1-benzothiophene-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0060	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(1-methylpiperidin-4-yl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0061	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-(piperidin-1-ylmethyl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0064	uM
5-chloro-6-[ethyl(oxan-4-yl)amino]-N-[(6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0065	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-(morpholin-4-ylmethyl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0078	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0079	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0140	uM
1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-(6-piperazin-1-yl-3-pyridinyl)indole-4-carboxamide	1151968: Inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED protein complex (unknown origin) using histone H3 peptide/S-adenosylmethionine as substrate after 2 hrs by TR-FRET assay	ic50	0.0160	uM
(3S,4R)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethyl-4-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]pyrrolidin-3-amine	1872375: Inhibition of PRC2 complex of EZH2-EED-SUZ12 (unknown origin) using human nucleosome as substrate incubated for 70 mins in presence of [3H]SAM	ic50	0.0180	uM
N-(furan-2-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	1802691: HMT Assay from Article 10.1038/nchembio.2304: “An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.”	ic50	0.0200	uM
5-bromo-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methylbenzamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0200	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0740	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[5,4-b]pyridine-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.1490	uM
(6R,7R)-6,7-dihydroxy-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	1151969: Competitive inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED/RbAp46/48 (unknown origin) using histone H3 peptide/varying concentration of S-adenosylmethionine as substrate after 2 hrs by Lineweaver-Burk plot analysis	ki	0.1940	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.3310	uM
(6R,7S)-6,7-dihydroxy-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	1151968: Inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED protein complex (unknown origin) using histone H3 peptide/S-adenosylmethionine as substrate after 2 hrs by TR-FRET assay	ic50	0.5200	uM
(2S,4R)-1-[(2S)-2-[4-[[4-[5-(furan-2-ylmethylamino)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]benzoyl]amino]butanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1928067: PROTAC activity at PRC2 catalytic core SUZ12/VHL in human DLBCL cells measured after 24 hrs by Western blot analysis	ec50	0.5900	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-(trifluoromethyl)-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	2.0000	uM
6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	1151968: Inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED protein complex (unknown origin) using histone H3 peptide/S-adenosylmethionine as substrate after 2 hrs by TR-FRET assay	ic50	4.8000	uM
1,6-dimethylnaphtho[1,2-g][1]benzofuran-10,11-dione	1151968: Inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED protein complex (unknown origin) using histone H3 peptide/S-adenosylmethionine as substrate after 2 hrs by TR-FRET assay	ic50	8.9000	uM
methyl (6S)-1,6-dimethyl-10,11-dioxo-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-6-carboxylate	1151968: Inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED protein complex (unknown origin) using histone H3 peptide/S-adenosylmethionine as substrate after 2 hrs by TR-FRET assay	ic50	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
ginger extract	decreases expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
kojic acid	decreases expression	1
trichostatin A	decreases expression	1
coumarin	increases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
mirdametinib	affects cotreatment, decreases reaction, increases response to substance	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
enzalutamide	affects binding, affects cotreatment, decreases reaction, decreases expression, increases reaction	1
jinfukang	decreases expression	1
4-acetylantroquinonol B	decreases expression	1
picoxystrobin	increases expression	1
(+)-JQ1 compound	decreases reaction, increases response to substance, affects cotreatment	1
GSK-2816126	increases reaction, affects binding, affects cotreatment, decreases reaction, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Curcumin	decreases expression	1

ChEMBL screening assays

51 unique, capped per target: 51 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5039022	Binding	Binding affinity to SUZ12 in human WSUDLCL2 cells assessed as thermal stability by measuring shift in temperature at 60 uM pretreated with proteasome inhibitor MG132 for 1 hr followed by compound addition incubated for 2 hrs by cellular the	Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2. — J Med Chem

Cellosaurus cell lines

12 cell lines: 8 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6W0	SEES3-1V human SUZ12, clone1	Embryonic stem cell	Male
CVCL_A6W1	SEES3-1V human SUZ12, clone2	Embryonic stem cell	Male
CVCL_A6W2	SEES3-1V human SUZ12, clone3	Embryonic stem cell	Male
CVCL_B2HY	Abcam HeLa SUZ12 KO	Cancer cell line	Female
CVCL_B7UL	e-hUVEC-4	Transformed cell line
CVCL_B7ZR	Abcam Raji SUZ12 KO	Cancer cell line	Male
CVCL_C0AJ	Abcam THP-1 SUZ12 KO	Cancer cell line	Male
CVCL_C7C7	Abcam PC-3 SUZ12 KO	Cancer cell line	Male
CVCL_D4AA	RsNF	Cancer cell line	Female
CVCL_E5GK	NF1-08-CL	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00104676	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00002931	PHASE2	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
NCT00301782	PHASE2	COMPLETED	Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors
NCT00432094	PHASE2	COMPLETED	Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
NCT00453232	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors
NCT00453310	PHASE2	COMPLETED	Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment
NCT00470366	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
NCT02300987	PHASE2	COMPLETED	A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder