EHMT2

Summary

EHMT2 (euchromatic histone lysine methyltransferase 2, HGNC:14129) is a protein-coding gene on chromosome 6p21.33, encoding Histone-lysine N-methyltransferase EHMT2 (Q96KQ7). Histone methyltransferase that specifically mono- and dimethylates ‘Lys-9’ of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.

This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10919 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 52
• Clinical variants (ClinVar): 179 total — 7 pathogenic
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_006709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14129
Approved symbol	EHMT2
Name	euchromatic histone lysine methyltransferase 2
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	G9A, Em:AF134726.3, NG36/G9a, KMT1C
Ensembl gene	ENSG00000204371
Ensembl biotype	protein_coding
OMIM	604599
Entrez	10919

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 29 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000375528, ENST00000375530, ENST00000375537, ENST00000395728, ENST00000436026, ENST00000461880, ENST00000463484, ENST00000465429, ENST00000477678, ENST00000478491, ENST00000480912, ENST00000494816, ENST00000892695, ENST00000892696, ENST00000892697, ENST00000892698, ENST00000892699, ENST00000892700, ENST00000892701, ENST00000892702, ENST00000892703, ENST00000892704, ENST00000892705, ENST00000892706, ENST00000892707, ENST00000920073, ENST00000920074, ENST00000920075, ENST00000920076, ENST00000920077, ENST00000920078, ENST00000962957, ENST00000962958, ENST00000962959, ENST00000962960, ENST00000962961

RefSeq mRNA: 11 — MANE Select: NM_006709 NM_001289413, NM_001318833, NM_001363689, NM_001395160, NM_001395161, NM_001395162, NM_001395163, NM_001395164, NM_001395165, NM_006709, NM_025256

CCDS: CCDS4725, CCDS4726, CCDS75425, CCDS87384

Canonical transcript exons

ENST00000375537 — 28 exons

Exon	Start	End
ENSE00001670006	31896263	31896516
ENSE00003468104	31884912	31885016
ENSE00003472568	31886775	31886897
ENSE00003479751	31892826	31892910
ENSE00003503840	31889468	31889602
ENSE00003511282	31887779	31887961
ENSE00003517655	31881014	31881092
ENSE00003518110	31888599	31888747
ENSE00003525044	31886581	31886682
ENSE00003536069	31888041	31888276
ENSE00003550532	31887577	31887659
ENSE00003552608	31884392	31884559
ENSE00003559177	31886995	31887101
ENSE00003563424	31883362	31883439
ENSE00003566553	31892694	31892734
ENSE00003576546	31880673	31880848
ENSE00003580154	31896606	31896824
ENSE00003598066	31882894	31883009
ENSE00003605472	31892407	31892562
ENSE00003612255	31888969	31889070
ENSE00003618393	31882699	31882785
ENSE00003631986	31883806	31883950
ENSE00003648584	31896923	31896989
ENSE00003655394	31889228	31889342
ENSE00003663269	31879759	31880264
ENSE00003672374	31884645	31884799
ENSE00003674338	31888363	31888506
ENSE00003978261	31897636	31897698

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0551 / max 165.9154, expressed in 1781 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72861	16.8456	1774
72860	0.9551	510
72859	0.5425	257
72857	0.3635	189
72858	0.3484	157

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	97.26	gold quality
ganglionic eminence	UBERON:0004023	97.21	gold quality
putamen	UBERON:0001874	97.11	gold quality
cortical plate	UBERON:0005343	97.01	gold quality
ventricular zone	UBERON:0003053	96.96	gold quality
right frontal lobe	UBERON:0002810	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.90	gold quality
caudate nucleus	UBERON:0001873	96.89	gold quality
cerebellar hemisphere	UBERON:0002245	96.66	gold quality
cerebellum	UBERON:0002037	96.64	gold quality
cerebellar cortex	UBERON:0002129	96.63	gold quality
temporal lobe	UBERON:0001871	96.31	gold quality
amygdala	UBERON:0001876	96.29	gold quality
anterior cingulate cortex	UBERON:0009835	96.17	gold quality
Ammon’s horn	UBERON:0001954	95.92	gold quality
primary visual cortex	UBERON:0002436	95.92	gold quality
hypothalamus	UBERON:0001898	95.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.56	gold quality
superior frontal gyrus	UBERON:0002661	95.34	gold quality
substantia nigra	UBERON:0002038	94.79	gold quality
body of uterus	UBERON:0009853	94.72	gold quality
brain	UBERON:0000955	94.53	gold quality
left testis	UBERON:0004533	94.35	gold quality
right uterine tube	UBERON:0001302	94.30	gold quality
right testis	UBERON:0004534	94.13	gold quality
right ovary	UBERON:0002118	94.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.90	gold quality
endocervix	UBERON:0000458	93.82	gold quality
pituitary gland	UBERON:0000007	93.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ACTR6
AURKAIP1
BCAS3
BIRC5	Unknown
CDH2
CDKN1A	Unknown
HBB	Activation
KMT2E
NCOA3
POLR1F
RUNX3	Activation
SIAH1	Repression
VAPB
ZNF217

Upstream regulators (CollecTRI, top): DNMT1, DNMT3A, DNMT3B, ESR1, HDAC1, JARID2, KDM5C, MECP2, MTA1, MYOD1, NFIL3, NR0B2, PRDM1, RELB, TCF3, TP53, ZEB2

miRNA regulators (miRDB)

36 targeting EHMT2, 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-6825-5P	99.96	69.81	3431
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-6818-5P	97.50	67.10	1167

Literature-anchored findings (GeneRIF, showing 40)

• interaction of G9a with a sequence-specific transcription factor that regulates gene repression through CDP/cut. (PMID:15269344)
• Phe at the position equivalent to Phe(281) of Neurospora crassa DIM-5 or Phe(1205) of human G9a allows the enzyme to perform di and tri-methylation, whereas a Tyr at this position is restrictive, inhibiting tri-methylation and yielding a mono- or di-MTase (PMID:15590646)
• Gfi1 associates with G9a and HDAC1 on the promoter of the cell cycle regulator p21Cip/WAF1, resulting in an increase in K9 dimethylation at histone H3 (PMID:16287849)
• results show human cytomegalovirus IE86 interacts with HDAC1 and histone methyltransferases G9a and Suvar(3-9)H1 and that coexpression of these chromatin remodeling enzymes with IE86 increases autorepression of the major immediate-early promoter (PMID:17005678)
• Direct cooperation between DNMT1 and G9a provides a mechanism of coordinated DNA and H3K9 methylation during cell division. (PMID:17085482)
• These studies establish a critical role for G9a methyltransferase, histone deacetylases, and the Swi/Snf-Brm complex in the SHP-mediated inhibition of hepatic bile acid synthesis via coordinated chromatin modification at target genes. (PMID:17145766)
• ZNF200 is a novel binding partner of G9a. (PMID:17584299)
• The results reveal the mechanism underlying CSB-mediated activation of ribosomal DNA transcription and link G9a-dependent histone methylation to Pol I transcription elongation through chromatin. (PMID:17707230)
• These data suggest that the 2 HMTs, SUV39H1 and G9a are required to perpetuate the malignant phenotype. (PMID:18446223)
• /EBPbeta as a direct substrate of G9a-mediated post-translational modification that alters the functional properties of C/EBPbeta during gene regulation. (PMID:18647749)
• G9a and HP1 couple histone and DNA methylation to TNFalpha transcription silencing during endotoxin tolerance (PMID:18809684)
• Hypoxia upregulates G9a histone methyltransferase & HDAC1. Overexpression of G9a & HDAC1 attenuated RUNX3 expression. The overexpression of G9a & HDAC1, but not their mutants, inhibited the nuclear localization & expression of RUNX3. (PMID:18850007)
• Chromodomain on Y-like (CDYL) is identified as a REST corepressor that physically bridges REST and the histone methylase G9a to repress transcription. (PMID:19061646)
• Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins (PMID:19144645)
• We found robust DNA hypomethylation in G9a/GLP knockdown of murine ES cells but a lack of DNA methylation changes in G9a/GLP knockdown human cancer cells; intriguingly, this distinction also extended to markers of global DNA methylation. (PMID:19531572)
• Data show that RelB induces facultative heterochromatin formation by directly interacting with the histone H3 lysine 9 methyltransferase G9a. (PMID:19690169)
• EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. (PMID:19776757)
• EHMT2 polymorphisms are associated with colorectal cancer. (PMID:19843671)
• G9a and Glp methylate lysine 373 in the tumor suppressor p53 (PMID:20118233)
• G9a is responsible for the transcriptional quiescence of latent HIV-1 provirus (PMID:20335163)
• Genome-wide analysis and microarray can identify genes that are specifical regulated by G9a. (PMID:20421388)
• Findings establish a functional contributio of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression. (PMID:20940408)
• Our results suggest that dysregulation of EHMT2 plays an important role in the growth regulation of cancer cells. (PMID:21847359)
• the coactivator and corepressor functions of G9a involve different G9a domains and different molecular mechanisms (PMID:21984853)
• study concludes that a subset of cancer-related Runx2 target genes require recruitment of G9a for their expression, but do not depend on its histone methyltransferase activity (PMID:22389001)
• Snail interacted with G9a, a major euchromatin methyltransferase responsible for H3K9me2, and recruited G9a and DNA methyltransferases to the E-cadherin promoter for DNA methylation. (PMID:22406531)
• data show that HMTase G9a negatively regulates JAK2 transcription and H3Y41 phosphorylation on the lmo2 promoter; and study provides new insights into G9a function in the regulation of hematopoiesis and leukemogenesis (PMID:22801367)
• findings indicate distinct mechanisms of G9a coactivator vs. corepressor functions in transcriptional regulation and provide insight into the molecular mechanisms of G9a coactivator function (PMID:23151507)
• With G9a and GLP1 as representative Protein methyltransferases (PMTs), it demonstrated the use of methionine analogues, a MAT variant and engineered PMTs for substrate labeling in vitro and genome-wide chromatin modifications within living cells. (PMID:23244065)
• G9a mediates E4BP4-dependent suppression of hepatic Fgf21 by enhancing histone methylation (H3K9me2) of the Fgf21 promoter (PMID:23283977)
• Histone-lysine methyltransferase EHMT2 is involved in proliferation, apoptosis, cell invasion, and DNA methylation of human neuroblastoma cells. (PMID:23466651)
• H3K9me3-positive grade II oligodendrogliomas, but not other tumor subtypes, show improved overall survival compared with H3K9me3-negative cases. (PMID:23481705)
• These findings suggest that h-CDYLb and G9a are cooperatively involved in hepatocellular carcinomas (PMID:23629948)
• Sumoylation of Sharp-1 exerts an impact on chromatin structure and transcriptional repression of muscle gene expression through recruitment of G9a. (PMID:23637228)
• Genome association studies identified EHMT2 as a new risk-associated loci for chronic hepatitis B on the HLA region of chromosome 6. (PMID:23760081)
• G9a inhibition may help overcome drug resistance in certain cancer cells. (PMID:23807219)
• G9a directly represses genes known to participate in the autophagic process. (PMID:23918802)
• all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A. (PMID:24019522)
• G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. (PMID:24315373)
• PRC2 and G9a/GLP interact physically and functionally. (PMID:24389103)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	ehmt2	ENSDARG00000102325
mus_musculus	Ehmt2	ENSMUSG00000013787
rattus_norvegicus	Ehmt2	ENSRNOG00000030630
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00020006
caenorhabditis_elegans		WBGENE00020919
caenorhabditis_elegans		WBGENE00021282

Paralogs (19): KMT2C (ENSG00000055609), SETD1A (ENSG00000099381), SUV39H1 (ENSG00000101945), EZH2 (ENSG00000106462), EZH1 (ENSG00000108799), NSD2 (ENSG00000109685), ASH1L (ENSG00000116539), KMT2A (ENSG00000118058), SETDB2 (ENSG00000136169), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), SUV39H2 (ENSG00000152455), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), KMT2B (ENSG00000272333)

Protein

Protein identifiers

Histone-lysine N-methyltransferase EHMT2 — Q96KQ7 (reviewed: Q96KQ7)

Alternative names: Euchromatic histone-lysine N-methyltransferase 2, HLA-B-associated transcript 8, Histone H3-K9 methyltransferase 3, Lysine N-methyltransferase 1C, Protein G9a

All UniProt accessions (5): Q96KQ7, A0A024RCN9, A2ABF8, A2ABF9, H0Y4K5

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that specifically mono- and dimethylates ‘Lys-9’ of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of ‘Lys-56’ of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates ‘Lys-27’ of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. Also able to mono- and dimethylate histone H1-4 at ‘Lys-26’ (H1.4K26me1 and H1.4K26me2, respectively). In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of ‘Lys-373’ of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.

Subunit / interactions. Heterodimer; heterodimerizes with EHMT1/GLP. Interacts with GFI1B and WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with UHRF1. Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. Interacts with PRDM9 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA. Interacts with SMYD5.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.

Post-translational modifications. Methylated at Lys-185; automethylated.

Domain organisation. The SET domain mediates interaction with WIZ. The ANK repeats bind H3K9me1 and H3K9me2. In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96KQ7-1	1	yes
Q96KQ7-2	2, NG36G9a-SPI
Q96KQ7-3	3, NG36

RefSeq proteins (11): NP_001276342, NP_001305762, NP_001350618, NP_001382089, NP_001382090, NP_001382091, NP_001382092, NP_001382093, NP_001382094, NP_006700, NP_079532 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR007728	Pre-SET_dom	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR038034	SET_EHMT2	Domain
IPR043550	EHMT1/EHMT2	Family
IPR046341	SET_dom_sf	Homologous_superfamily
IPR047762	EHMT_CRR	Domain

Pfam: PF00023, PF00856, PF05033, PF12796, PF21533

Enzyme classification (BRENDA):

• EC 2.1.1.355 — [histone H3]-lysine9 N-trimethyltransferase (BRENDA: 12 organisms, 83 substrates, 52 inhibitors, 11 Km, 11 kcat entries)
• EC 2.1.1.356 — [histone H3]-lysine27 N-trimethyltransferase (BRENDA: 12 organisms, 23 substrates, 3 inhibitors, 14 Km, 13 kcat entries)
• EC 2.1.1.367 — [histone H3]-lysine9 N-methyltransferase (BRENDA: 5 organisms, 4 substrates, 19 inhibitors, 0 Km, 0 kcat entries)
• EC 2.1.1.368 — [histone H3]-lysine9 N-dimethyltransferase (BRENDA: 6 organisms, 10 substrates, 20 inhibitors, 8 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.53–0.68	4
(+/-)-2’,3’-DIBENZYL-S-ADENOSYL-L-METHIONINE	0.072–0.917	3
(+/-)-3’-BENZYL-S-ADENOSYL-L-METHIONINE	0.086–2.8	3
HISTONE H3(K27)	0.2762–3.9	3
S-ADENOSYL-L-METHIONINE	0.06–0.126	3
HISTONE H3	0.0003–0.0009	2
(+/-)-2’-BENZYL-S-ADENOSYL-L-METHIONINE	0.086–0.128	2
[HISTONE H3 PEPTIDE 1-15]-L-LYSINE9	0.28–0.41	2
[HISTONE H3 PEPTIDE 1-15]-N6-METHYL-L-LYSINE9	0.41–0.59	2
BIOTINYL-MARTKQTARKSTGGKAPRKQ	0.0074	1
HISTONE H3 (1-13)	0.0011	1
HISTONE H3 (T11PHOS)	0.0006	1
HISTONE H3(K27A)	0.0002	1
HISTONE H3(K4A)	0.0002	1
HISTONE K4-ACETYLK9	0.0022	1

Catalyzed reactions (Rhea), 4 shown:

• L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60280)
• N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60284)
• L-lysyl(56)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(56)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:85519)
• N(6)-methyl-L-lysyl(56)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(56)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:85919)

UniProt features (147 total): binding site 39, strand 29, modified residue 18, helix 12, compositionally biased region 8, repeat 7, region of interest 6, mutagenesis site 6, turn 5, domain 3, sequence conflict 3, cross-link 3, splice variant 3, sequence variant 2, initiator methionine 1, chain 1, site 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5VSC	X-RAY DIFFRACTION	1.4
7XUD	X-RAY DIFFRACTION	1.45
5JIY	X-RAY DIFFRACTION	1.48
7X73	X-RAY DIFFRACTION	1.49
8Z7C	X-RAY DIFFRACTION	1.52
8Z7E	X-RAY DIFFRACTION	1.54
8Z7D	X-RAY DIFFRACTION	1.58
5VSE	X-RAY DIFFRACTION	1.6
5JHN	X-RAY DIFFRACTION	1.67
7XUC	X-RAY DIFFRACTION	1.67
3K5K	X-RAY DIFFRACTION	1.7
5T0K	X-RAY DIFFRACTION	1.7
5JJ0	X-RAY DIFFRACTION	1.72
5TTF	X-RAY DIFFRACTION	1.72
5V9I	X-RAY DIFFRACTION	1.74
9YKS	X-RAY DIFFRACTION	1.79
2O8J	X-RAY DIFFRACTION	1.8
7DCF	X-RAY DIFFRACTION	1.8
9KLB	X-RAY DIFFRACTION	1.81
5JIN	X-RAY DIFFRACTION	1.85
9WRI	X-RAY DIFFRACTION	1.85
7XUA	X-RAY DIFFRACTION	1.87
5T0M	X-RAY DIFFRACTION	1.9
6MM1	X-RAY DIFFRACTION	1.9
7BTV	X-RAY DIFFRACTION	2
7XUB	X-RAY DIFFRACTION	2
8VV8	X-RAY DIFFRACTION	2
4NVQ	X-RAY DIFFRACTION	2.03
9KLC	X-RAY DIFFRACTION	2.15
7T7L	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KQ7-F1	69.25	0.45

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): 1067 (histone h3k9me binding)

Ligand- & substrate-binding residues (39): 426; 428; 446; 459; 481; 484; 491; 494; 497; 509; 517; 520 …

Post-translational modifications (21): 2, 40, 44, 47, 140, 173, 185, 185, 232, 242, 246, 350, 412, 413, 555, 569, 1204, 1210, 219, 229 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
786	abolishes binding to histone h3k9me without affecting the histone methyltransferase activity.
791	abolishes binding to histone h3k9me without affecting the histone methyltransferase activity.
794	abolishes binding to histone h3k9me without affecting the histone methyltransferase activity.
817	impairs binding to histone h3k9me.
824	abolishes binding to histone h3k9me without affecting the histone methyltransferase activity.
852	impairs binding to histone h3k9me.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9843970	Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex

MSigDB gene sets: 271 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, GOBP_VACUOLE_ORGANIZATION, PAL_PRMT5_TARGETS_UP, CMYB_01, GOBP_ADULT_BEHAVIOR, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA replication (GO:0006275), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), synaptonemal complex assembly (GO:0007130), spermatid development (GO:0007286), cellular response to starvation (GO:0009267), fertilization (GO:0009566), peptidyl-lysine dimethylation (GO:0018027), chromosome condensation (GO:0030261), organ growth (GO:0035265), phenotypic switching (GO:0036166), epigenetic regulation of gene expression (GO:0040029), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), behavioral response to cocaine (GO:0048148), oocyte development (GO:0048599), neuron fate specification (GO:0048665), cellular response to cocaine (GO:0071314), negative regulation of autophagosome assembly (GO:1902902), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), methylation (GO:0032259)

GO Molecular Function (19): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), transcription corepressor binding (GO:0001222), p53 binding (GO:0002039), zinc ion binding (GO:0008270), protein-lysine N-methyltransferase activity (GO:0016279), histone H3K9 methyltransferase activity (GO:0046974), histone H3K27 methyltransferase activity (GO:0046976), C2H2 zinc finger domain binding (GO:0070742), H1-4K26 methyltransferase activity (GO:0140189), histone H3K56 methyltransferase activity (GO:0140759), histone H3K9 monomethyltransferase activity (GO:0140948), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872), histone H3 methyltransferase activity (GO:0140938), histone H3K9me2 methyltransferase activity (GO:0140947)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), chromosome (GO:0005694), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Generic Transcription Pathway	2
Cellular Senescence	1
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
Regulation of TP53 Activity	1
RNA Polymerase I Promoter Clearance	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-lysine N-methyltransferase activity	3
histone H3 methyltransferase activity	3
germ cell development	2
response to cocaine	2
protein methyltransferase activity	2
histone H3K9 methyltransferase activity	2
cellular anatomical structure	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA replication	1
regulation of DNA metabolic process	1
constitutive heterochromatin formation	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
spermatid differentiation	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
sexual reproduction	1
reproductive process	1
peptidyl-lysine methylation	1
chromosome organization	1
multicellular organismal process	1
developmental growth	1
cellular process	1
chromatin remodeling	1
regulation of gene expression	1
negative regulation of gene expression, epigenetic	1
adult behavior	1
oocyte differentiation	1
cell fate specification	1
neuron fate commitment	1
cellular response to alkaloid	1
cellular response to oxygen-containing compound	1
autophagosome assembly	1
negative regulation of macroautophagy	1

Protein interactions and networks

STRING

3964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EHMT2	HDAC1	Q13547	996
EHMT2	DNMT1	P26358	995
EHMT2	SNAI1	O95863	991
EHMT2	DNMT3A	Q9Y6K1	991
EHMT2	UHRF1	Q96T88	991
EHMT2	KDM1A	O60341	989
EHMT2	RCOR1	Q9UKL0	985
EHMT2	KDM5C	P41229	985
EHMT2	EHMT1	Q9H9B1	979
EHMT2	CDYL	Q9Y232	979
EHMT2	CBX3	Q13185	966
EHMT2	SUV39H1	O43463	964
EHMT2	H3-3A	P06351	962
EHMT2	H3C1	P02295	962
EHMT2	SETDB1	Q15047	949

IntAct

293 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	EHMT2	psi-mi:“MI:0914”(association)	0.840
EHMT2	HDAC1	psi-mi:“MI:0915”(physical association)	0.840
PLOD3	EHMT2	psi-mi:“MI:0915”(physical association)	0.830
CTBP1	KDM1A	psi-mi:“MI:0914”(association)	0.790
ZNF462	EHMT2	psi-mi:“MI:0915”(physical association)	0.740
EHMT2	KLF12	psi-mi:“MI:0915”(physical association)	0.740
EHMT2	WIZ	psi-mi:“MI:0914”(association)	0.730
CHD1	KDM1A	psi-mi:“MI:0915”(physical association)	0.700
MTA3	MBD3	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
MTA2	EHMT2	psi-mi:“MI:0407”(direct interaction)	0.680
KLF3	EHMT2	psi-mi:“MI:0915”(physical association)	0.660
MTA1	ZEB2	psi-mi:“MI:0914”(association)	0.610
MTA3	GATA3	psi-mi:“MI:0914”(association)	0.610
EHMT2	GATA3	psi-mi:“MI:0914”(association)	0.610
GATA3	EHMT2	psi-mi:“MI:0914”(association)	0.610
GATA3	EHMT2	psi-mi:“MI:0407”(direct interaction)	0.610
MTA3	EHMT2	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (466): EHMT2 (Two-hybrid), EHMT2 (Two-hybrid), EHMT2 (Two-hybrid), EHMT2 (Two-hybrid), EHMT2 (Two-hybrid), C10orf12 (Two-hybrid), CHCHD2 (Two-hybrid), KLF3 (Two-hybrid), FAM161A (Two-hybrid), NAPRT (Two-hybrid), ZNF785 (Two-hybrid), ZBTB38 (Two-hybrid), RD3 (Two-hybrid), EHMT2 (Affinity Capture-RNA), EHMT2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1W2PQ72, A7J1T0, A7J1T2, A7MBB4, A8MZ59, D3ZXW3, M0R5D6, O36371, O43283, O43310, O73622, O95073, P03177, P10242, P21705, P46200, Q0P4H6, Q1HKZ5, Q1HVD1, Q1LVK9, Q22811, Q2NKQ1, Q3KSQ2, Q3UPF5, Q535K8, Q562B4, Q567C6, Q5R8X7, Q5ZI27, Q6DGX3, Q6INH1, Q6J1H4, Q6PEE2, Q6ZTZ1, Q71M44, Q7SXL7, Q80T85, Q8BFX3, Q8BIL2, Q8BKE5

Diamond homologs: A0A1L7TZE5, A4IGY9, A7E2Z2, A8XI75, J9VWH9, O43463, O54864, O60016, O65312, O82175, O88491, O88974, O96028, P20659, P42124, P45975, P46995, P55200, P70351, P93831, Q03164, Q06ZW3, Q08BR4, Q08BS4, Q0VD24, Q15047, Q15910, Q24742, Q28CQ7, Q28D84, Q294B9, Q2NL30, Q32PH7, Q4PB36, Q4R381, Q4R3E0, Q4V863, Q53H47, Q5DW34, Q5F3W5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EHMT2	“up-regulates quantity by expression”	HBB	“transcriptional regulation”
2-cyclohexyl-6-methoxy-N-(1-propan-2-yl-4-piperidinyl)-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine	“down-regulates activity”	EHMT2	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
Regulation of endogenous retroelements	7	29.6×	3e-07
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	6	26.2×	3e-06
Regulation of PTEN gene transcription	8	16.4×	1e-06
Deactivation of the beta-catenin transactivating complex	6	16.1×	4e-05
RNA Polymerase I Transcription Initiation	6	15.4×	5e-05
HDACs deacetylate histones	11	15.2×	3e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	9	15.2×	5e-07
Gastrulation	5	14.9×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	6	39.3×	9e-07
negative regulation of miRNA transcription	5	26.7×	1e-04
negative regulation of gene expression, epigenetic	5	17.1×	7e-04
positive regulation of miRNA transcription	6	14.9×	2e-04
positive regulation of stem cell population maintenance	5	14.7×	1e-03
heterochromatin formation	5	10.9×	4e-03
chromatin remodeling	16	10.0×	9e-10
chromatin organization	9	7.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	126
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2687731	NM_006709.5(EHMT2):c.3229G>T (p.Ala1077Ser)	Pathogenic
4057266	NM_006709.5(EHMT2):c.3335A>G (p.Asn1112Ser)	Pathogenic
4057267	NM_006709.5(EHMT2):c.3472T>C (p.Phe1158Leu)	Pathogenic
4057268	NM_006709.5(EHMT2):c.3485A>G (p.Lys1162Arg)	Pathogenic
4057269	NM_006709.5(EHMT2):c.3225_3236del (p.Glu1076_Val1079del)	Pathogenic
4057270	NM_006709.5(EHMT2):c.3487_3492del (p.Ser1163_Lys1164del)	Pathogenic
4813307	NM_006709.5(EHMT2):c.3229G>A (p.Ala1077Thr)	Pathogenic

SpliceAI

3482 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31880260:CAAAC:C	acceptor_gain	1.0000
6:31880261:AAAC:A	acceptor_gain	1.0000
6:31880262:AAC:A	acceptor_gain	1.0000
6:31880262:AACC:A	acceptor_loss	1.0000
6:31880263:AC:A	acceptor_gain	1.0000
6:31880263:ACC:A	acceptor_loss	1.0000
6:31880264:CC:C	acceptor_gain	1.0000
6:31880264:CCTG:C	acceptor_loss	1.0000
6:31880265:C:CC	acceptor_gain	1.0000
6:31880269:C:CT	acceptor_gain	1.0000
6:31880270:A:T	acceptor_gain	1.0000
6:31880667:TCTCA:T	donor_loss	1.0000
6:31880669:TCACC:T	donor_loss	1.0000
6:31880670:CACCC:C	donor_loss	1.0000
6:31880671:A:AC	donor_gain	1.0000
6:31880671:AC:A	donor_gain	1.0000
6:31880672:C:CA	donor_gain	1.0000
6:31880672:C:CC	donor_gain	1.0000
6:31880676:AGCT:A	donor_gain	1.0000
6:31880677:G:C	donor_gain	1.0000
6:31880682:T:TA	donor_gain	1.0000
6:31880683:C:CA	donor_gain	1.0000
6:31880684:C:A	donor_gain	1.0000
6:31880844:CCATC:C	acceptor_gain	1.0000
6:31880845:CATC:C	acceptor_gain	1.0000
6:31880845:CATCC:C	acceptor_gain	1.0000
6:31880847:TC:T	acceptor_gain	1.0000
6:31880848:CC:C	acceptor_gain	1.0000
6:31880849:C:CC	acceptor_gain	1.0000
6:31881009:CTCA:C	donor_loss	1.0000

AlphaMissense

7863 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31880188:G:C	H1177D	1.000
6:31880189:C:A	K1176N	1.000
6:31880189:C:G	K1176N	1.000
6:31880192:G:C	C1175W	1.000
6:31880193:C:A	C1175F	1.000
6:31880193:C:G	C1175S	1.000
6:31880193:C:T	C1175Y	1.000
6:31880194:A:G	C1175R	1.000
6:31880194:A:T	C1175S	1.000
6:31880207:A:C	C1170W	1.000
6:31880208:C:A	C1170F	1.000
6:31880208:C:G	C1170S	1.000
6:31880208:C:T	C1170Y	1.000
6:31880209:A:G	C1170R	1.000
6:31880209:A:T	C1170S	1.000
6:31880213:G:C	C1168W	1.000
6:31880214:C:A	C1168F	1.000
6:31880214:C:G	C1168S	1.000
6:31880214:C:T	C1168Y	1.000
6:31880215:A:C	C1168G	1.000
6:31880215:A:G	C1168R	1.000
6:31880215:A:T	C1168S	1.000
6:31880219:G:C	F1166L	1.000
6:31880219:G:T	F1166L	1.000
6:31880220:A:C	F1166C	1.000
6:31880220:A:G	F1166S	1.000
6:31880221:A:G	F1166L	1.000
6:31880221:A:T	F1166I	1.000
6:31880231:T:A	K1162N	1.000
6:31880231:T:G	K1162N	1.000

dbSNP variants (sampled 300 via entrez): RS1000109467 (6:31885525 A>T), RS1000164594 (6:31881238 T>C), RS1000225905 (6:31881894 A>G), RS1000468295 (6:31881539 A>G), RS1000571408 (6:31887385 C>T), RS1000774469 (6:31888627 C>A,T), RS1000861409 (6:31894193 C>G), RS1000872135 (6:31881515 A>G), RS1000891025 (6:31894457 A>G), RS1000996521 (6:31886631 C>T), RS1001552850 (6:31897804 C>A,G,T), RS1002046332 (6:31890000 G>A), RS1002064888 (6:31897623 T>A,C,G), RS1002140901 (6:31883261 G>A,C), RS1002353804 (6:31892667 G>A)

Disease associations

OMIM: gene MIM:604599 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST000984_13	Idiopathic membranous nephropathy	3.000000e-46
GCST001512_6	Economic and political preferences (environmentalism)	6.000000e-06
GCST001812_2	Epstein-Barr virus immune response (EBNA-1)	2.000000e-10
GCST002068_5	Chronic hepatitis B infection	7.000000e-13
GCST002879_6	Chronic hepatitis B infection	1.000000e-06
GCST003527_1	Anti-thyroid drug induced agranulocytosis	2.000000e-11
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004505_37	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-17
GCST004508_41	Waist-to-hip ratio adjusted for BMI in non-smokers	2.000000e-10
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_162	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005899_1	Type 2 diabetes	3.000000e-10
GCST006190_17	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-10
GCST006190_18	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0007838	response to anti-thyroid drug
EFO:0004318	smoking behavior
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0009130	clostridium difficile infection
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3885593 (PROTEIN FAMILY), CHEMBL5739548 (PROTEIN-PROTEIN INTERACTION), CHEMBL6032 (SINGLE PROTEIN), CHEMBL6066145 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 244,003 (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
CHEMBL225071	RALTITREXED	4	96,748
CHEMBL3414621	TAZEMETOSTAT	4	1,869
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL51085	EBSELEN	3	13,237
CHEMBL107217	DITIOCARB SODIUM	2	12,033
CHEMBL120563	THIRAM	2	79,340
CHEMBL1214186	SINEFUNGIN	2	2,165

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs652888	Toxicity	3	Antithyroid Preparations	Agranulocytosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs652888	EHMT2	3	0.00	1	Antithyroid Preparations

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
UNC0321	Inhibition	10.2	pKi
UNC0642	Inhibition	8.6	pIC50
A-366	Inhibition	8.48	pIC50
CM-272	Inhibition	8.1	pIC50
UNC0638	Inhibition	7.82	pIC50
BIX-01294	Inhibition	5.77	pIC50
BRD9539	Inhibition	5.2	pIC50

Binding affinities (BindingDB)

23 measured of 49 human assays (49 total across all organisms); most potent 23 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US10407423, Compound 1-02	IC50	300 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-06	IC50	300 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 3-04	IC50	300 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 1-03	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 1-05	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-02	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-05	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-07	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-08	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-09	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-10	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-12	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 3-02	IC50	750 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
CHEMBL1222849	IC50	1700 nM
chaetocin	IC50	2500 nM
CHEMBL2311579	IC50	3300 nM
US10407423, Compound 2-03	IC50	5500 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-11	IC50	5500 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 2-13	IC50	5500 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 3-01	IC50	5500 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
US10407423, Compound 3-03	IC50	5500 nM	US-10407423: Compounds as inhibitors of DNA methyltransferases
CHEMBL2315526	IC50	7200 nM
CHEMBL2315523	IC50	23500 nM

ChEMBL bioactivities

901 potent at pChembl≥5 of 972 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.38	IC50	0.42	nM	CHEMBL5437232
9.31	IC50	0.49	nM	CHEMBL5403007
9.30	IC50	0.5	nM	CHEMBL4170225
9.30	IC50	0.5	nM	CHEMBL4162206
9.29	IC50	0.51	nM	CHEMBL2441082
9.28	IC50	0.53	nM	CHEMBL5405913
9.28	IC50	0.52	nM	CHEMBL5424749
9.15	IC50	0.7	nM	CHEMBL4162206
9.15	IC50	0.71	nM	CHEMBL5416767
9.05	IC50	0.9	nM	CHEMBL3109639
9.00	IC50	1	nM	CHEMBL3109631
8.80	IC50	1.6	nM	CHEMBL5187766
8.77	IC50	1.7	nM	CHEMBL5435285
8.74	IC50	1.8	nM	CHEMBL5396581
8.70	IC50	2	nM	CHEMBL4159604
8.70	IC50	2	nM	CHEMBL4160008
8.70	IC50	2	nM	CHEMBL1829295
8.68	IC50	2.1	nM	CHEMBL5414343
8.62	IC50	2.4	nM	CHEMBL5195846
8.60	IC50	2.5	nM	CHEMBL1231795
8.60	IC50	2.5	nM	CHEMBL5433429
8.59	Ki	2.6	nM	CHEMBL576781
8.55	IC50	2.8	nM	CHEMBL3109630
8.54	IC50	2.9	nM	CHEMBL5410162
8.54	IC50	2.9	nM	TAZEMETOSTAT
8.52	IC50	3	nM	CHEMBL2441078
8.52	IC50	3	nM	CHEMBL3109630
8.52	IC50	3	nM	CHEMBL4171233
8.52	IC50	3	nM	CHEMBL4173626
8.52	Ki	3	nM	CHEMBL1231795
8.49	IC50	3.25	nM	CHEMBL4795328
8.48	IC50	3.3	nM	CHEMBL3109630
8.46	IC50	3.51	nM	CHEMBL5435375
8.44	Ki	3.6	nM	CHEMBL4454542
8.43	Ki	3.7	nM	CHEMBL1231795
8.43	Ki	3.7	nM	CHEMBL2441082
8.43	IC50	3.7	nM	CHEMBL3109637
8.43	IC50	3.75	nM	CHEMBL1231795
8.41	IC50	3.9	nM	CHEMBL5401784
8.40	IC50	4	nM	CHEMBL2441077
8.40	IC50	4	nM	CHEMBL4287479
8.40	IC50	4	nM	CHEMBL4865830
8.40	IC50	4	nM	CHEMBL1829305
8.40	IC50	4	nM	CHEMBL6143682
8.37	IC50	4.31	nM	CHEMBL4741874
8.36	IC50	4.4	nM	CHEMBL5207914
8.32	IC50	4.8	nM	CHEMBL3109634
8.30	IC50	5	nM	CHEMBL3109632
8.30	IC50	5	nM	CHEMBL4211688
8.30	IC50	5	nM	CHEMBL6142996

PubChem BioAssay actives

788 with measured affinity, of 1694 total; 50 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
N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]but-2-ynamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0004	uM
2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1505786: Non-competitive inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of 2 to 640 uM SAM by TR-FRET assay	ic50	0.0005	uM
6-methoxy-N-(1-methylpiperidin-4-yl)-2-(5-methyl-1H-pyrrol-2-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1505768: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0005	uM
N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]prop-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0005	uM
N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]-2-methylprop-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0005	uM
(E)-N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]but-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0005	uM
2-(4,4-difluoropiperidin-1-yl)-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0005	uM
N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]propanamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0007	uM
5-methoxy-3,3-dimethyl-6-(3-pyrrolidin-1-ylpropoxy)indol-2-amine	1065266: Inhibition of G9a (unknown origin) using biotinylated-histone H3(1-21) peptide as substrate after 3 hrs by AlphaLISA assay	ic50	0.0009	uM
5’-methoxy-6’-[(1-methylpyrrolidin-3-yl)methoxy]spiro[cyclobutane-1,3’-indole]-2’-amine	1065266: Inhibition of G9a (unknown origin) using biotinylated-histone H3(1-21) peptide as substrate after 3 hrs by AlphaLISA assay	ic50	0.0010	uM
N’-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]ethane-1,2-diamine	1861703: Inhibition of G9a (unknown origin)	ic50	0.0016	uM
2-chloro-N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]methyl]acetamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0017	uM
N-[(5,6-dimethyl-3-pyridinyl)methyl]-2-(4-fluorophenyl)-2-piperidin-1-ylacetamide	2038518: Inhibition of N-terminal GST-tagged human recombinant G9a (785 to 1210 residues) expressed in baculovirus-infected Sf9 cells using biotinylated histone H3 peptide substrate incubated for 2 hrs by AlphaLISA assay	ic50	0.0018	uM
2-cyclohexyl-6-methoxy-N-(1-methylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1505768: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0020	uM
2-(5-ethylfuran-2-yl)-6-methoxy-N-(1-methylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1381130: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0020	uM
6-methoxy-2-(4-propan-2-yl-1,4-diazepan-1-yl)-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	618483: Inhibition of G9a assessed as hydrolysis of S-adenosyl-L-homocysteine after 2 mins by SAHH-coupled fluorescence assay	ic50	0.0020	uM
4-methyl-6-[4-[[4-(pyrrolidin-1-ylmethyl)thiophen-2-yl]methyl]piperazin-1-yl]pyrimidin-2-amine	2038518: Inhibition of N-terminal GST-tagged human recombinant G9a (785 to 1210 residues) expressed in baculovirus-infected Sf9 cells using biotinylated histone H3 peptide substrate incubated for 2 hrs by AlphaLISA assay	ic50	0.0021	uM
6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1861703: Inhibition of G9a (unknown origin)	ic50	0.0024	uM
5-chloro-N-[(4S)-1-ethyl-4-methoxypyrrolidin-3-yl]-1H-indole-2-carboxamide	2038518: Inhibition of N-terminal GST-tagged human recombinant G9a (785 to 1210 residues) expressed in baculovirus-infected Sf9 cells using biotinylated histone H3 peptide substrate incubated for 2 hrs by AlphaLISA assay	ic50	0.0025	uM
2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	1248877: Inhibition of G9a (unknown origin) using [histone H3 1 to 25 residues] and SAM substrate by scintillation proximity assay	ic50	0.0025	uM
6-methoxy-2-piperidin-1-yl-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	777198: Inhibition of lysine methyltransferase G9a (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay	ic50	0.0025	uM
2-(azepan-1-yl)-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	777198: Inhibition of lysine methyltransferase G9a (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay	ic50	0.0025	uM
6-methoxy-2-morpholin-4-yl-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	777198: Inhibition of lysine methyltransferase G9a (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay	ic50	0.0025	uM
7-[3-(dimethylamino)propoxy]-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine	1320661: Inhibition of G9a (unknown origin) using histone H3 (1 to 25 residues) as substrate preincubated for 2 mins followed by substrate addition measured for 20 mins by SAHH-coupled assay	ki	0.0026	uM
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine	1947845: Inhibition of G9a (unknown origin)	ic50	0.0027	uM
5’-methoxy-6’-(3-pyrrolidin-1-ylpropoxy)spiro[cyclobutane-1,3’-indole]-2’-amine	1861703: Inhibition of G9a (unknown origin)	ic50	0.0028	uM
3-[[[2-(4,4-difluoropiperidin-1-yl)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]amino]methyl]-4,6-dimethyl-1H-pyridin-2-one	1987441: Inhibition of human recombinant EHMT2 G9a using SAM as substrate incubated for 1 hr by microplate luminescence based HMT assay	ic50	0.0029	uM
6-methoxy-2-(5-methylfuran-2-yl)-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1505768: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0030	uM
2-(5-ethylfuran-2-yl)-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1505768: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0030	uM
N-(1-cyclopropylpiperidin-4-yl)-2-(4,4-difluoropiperidin-1-yl)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	777198: Inhibition of lysine methyltransferase G9a (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay	ic50	0.0030	uM
N-(1-benzylpiperidin-4-yl)-7-[3-(dimethylamino)propoxy]-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine	1415879: Inhibition of human G9a using biotinylated peptide H3( 1 to 25 residues) as substrate measured after 15 mins in presence of [3H]-SAM by scintillation proximity assay	ic50	0.0030	uM
2-N-[4-(difluoromethoxy)-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-4-N,6-dimethylpyrimidine-2,4-diamine	1722379: Inhibition G9a (unknown origin)	ic50	0.0032	uM
N-[4-[(1-cyclohexylpiperidin-4-yl)amino]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-yl]-N-methylprop-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0035	uM
2-cyclohexyl-7-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-8-(3-pyrrolidin-1-ylpropoxy)-3H-1,4-benzodiazepin-5-amine	1602430: Competitive inhibition of recombinant human G9a using biotinylated-Histone H3 peptide (1 to 21 residues) as substrate after 30 mins in presence of varying concentration of SAM by Lineweaver-Burk plot analysis	ki	0.0036	uM
6’-[3-[(3R)-3-fluoropyrrolidin-1-yl]propoxy]-5’-methoxyspiro[cyclobutane-1,3’-indole]-2’-amine	1065266: Inhibition of G9a (unknown origin) using biotinylated-histone H3(1-21) peptide as substrate after 3 hrs by AlphaLISA assay	ic50	0.0037	uM
N-[6-methoxy-4-[(1-propylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-yl]-N-methylprop-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0039	uM
N-hydroxy-2-[4-[[[6-methoxy-2-methyl-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]amino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1775567: Inhibition of human G9a enzyme using histone monomethyl-H3K9 peptide as substrate incubated for 1 hr in presence of SAM by TR-FRET assay	ic50	0.0040	uM
6-methoxy-2-(4-methylpiperazin-1-yl)-7-(3-piperidin-1-ylpropoxy)-N-(1-propan-2-ylpiperidin-4-yl)quinazolin-4-amine	1415879: Inhibition of human G9a using biotinylated peptide H3( 1 to 25 residues) as substrate measured after 15 mins in presence of [3H]-SAM by scintillation proximity assay	ic50	0.0040	uM
N-[1-(cyclohexylmethyl)piperidin-4-yl]-6-methoxy-7-(3-piperidin-1-ylpropoxy)-2-(4-propan-2-yl-1,4-diazepan-1-yl)quinazolin-4-amine	2038510: Inhibition of G9a (unknown origin)	ic50	0.0040	uM
N-(1-cyclopropylpiperidin-4-yl)-2-(1,1-dioxo-1,4-thiazinan-4-yl)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	777198: Inhibition of lysine methyltransferase G9a (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay	ic50	0.0040	uM
2-N-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-4-N,6-dimethylpyrimidine-2,4-diamine	1722379: Inhibition G9a (unknown origin)	ic50	0.0043	uM
N-[6-methoxy-4-[(1-propan-2-ylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-yl]-N-methylprop-2-enamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0044	uM
6’-[3-(3-fluoroazetidin-1-yl)propoxy]-5’-methoxyspiro[cyclobutane-1,3’-indole]-2’-amine	1065266: Inhibition of G9a (unknown origin) using biotinylated-histone H3(1-21) peptide as substrate after 3 hrs by AlphaLISA assay	ic50	0.0048	uM
2-(5-ethylfuran-2-yl)-6-methoxy-N-[(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)methyl]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine	1381130: Inhibition of human G9a using biotinylated-H3K9 peptide as substrate after 1 hr in presence of SAM by TR-FRET assay	ic50	0.0050	uM
2-(4-ethyl-1,4-diazepan-1-yl)-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	618483: Inhibition of G9a assessed as hydrolysis of S-adenosyl-L-homocysteine after 2 mins by SAHH-coupled fluorescence assay	ic50	0.0050	uM
5’-methoxy-6’-[(1-methylpyrrolidin-2-yl)methoxy]spiro[cyclobutane-1,3’-indole]-2’-amine	1065266: Inhibition of G9a (unknown origin) using biotinylated-histone H3(1-21) peptide as substrate after 3 hrs by AlphaLISA assay	ic50	0.0050	uM
N-[2-[[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]amino]ethyl]acetamide	1861703: Inhibition of G9a (unknown origin)	ic50	0.0052	uM
3-[[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]amino]propanamide	1861708: Inhibition of G9a (unknown origin) assessed as effect on H3K9 methylation by cell based assay	ic50	0.0057	uM
2-chloro-N-[[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-yl]methyl]acetamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0057	uM
N-[6-methoxy-4-[(1-methylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-yl]-N-methylpropanamide	1990867: Inhibition of G9a (unknown origin) by AlphaLISA assay	ic50	0.0058	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
sodium arsenite	affects binding, decreases reaction, increases reaction, affects cotreatment, decreases expression (+2 more)	5
bisphenol A	decreases expression, decreases methylation, increases expression	4
BIX 01294	decreases activity, decreases expression, affects cotreatment, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
Doxorubicin	affects binding, increases reaction, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
Batroxase, Bothrops atrox	increases expression	1
UNC0642	decreases activity	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	increases expression	1
manganese chloride	increases abundance, increases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
1-aminomethylphosphonic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1

ChEMBL screening assays

442 unique, capped per target: 435 binding, 6 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3390897	Binding	Inhibition of G9a/GLP in human MDA-MB-231 cells assessed as reduction of H3K9me2 level after 48 hrs by flow cytometric analysis	Development of second generation epigenetic agents — Medchemcomm
CHEMBL1738442	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Histone Lysine Methyltransferase G9a. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504404]	PubChem BioAssay data set
CHEMBL4416354	ADMET	Inhibition of human G9a expressed in Escherichia coli assessed as reduction in methylated histone H3 full length using histone H3 full length level as substrate in presence of [3H] SAM incubated for 120 mins by scintillation counting	High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT). — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7X3	Abcam Raji EHMT2 KO	Cancer cell line	Male
CVCL_B9VG	Abcam HeLa EHMT2 KO	Cancer cell line	Female
CVCL_B9XP	Abcam THP-1 EHMT2 KO	Cancer cell line	Male
CVCL_C6ZJ	Abcam PC-3 EHMT2 KO	Cancer cell line	Male
CVCL_D9E4	Ubigene HEK293 EHMT2 KO	Transformed cell line	Female
CVCL_KV98	InCELL Hunter A549 G9a Methyltransferase	Cancer cell line	Male
CVCL_SL56	HAP1 EHMT2 (-) 1	Cancer cell line	Male
CVCL_SL57	HAP1 EHMT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

202 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
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
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
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
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
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