PRMT6

Summary

PRMT6 (protein arginine methyltransferase 6, HGNC:18241) is a protein-coding gene on chromosome 1p13.3, encoding Protein arginine N-methyltransferase 6 (Q96LA8). Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA.

The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity.

Source: NCBI Gene 55170 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18241
Approved symbol	PRMT6
Name	protein arginine methyltransferase 6
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10559
Ensembl gene	ENSG00000198890
Ensembl biotype	protein_coding
OMIM	608274
Entrez	55170

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000370078, ENST00000649727, ENST00000650338

RefSeq mRNA: 1 — MANE Select: NM_018137 NM_018137

CCDS: CCDS41360

Canonical transcript exons

ENST00000370078 — 1 exons

Exon	Start	End
ENSE00001451674	107056674	107059294

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 87.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4722 / max 125.8688, expressed in 1745 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4313	13.4364	1745
4314	0.0358	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.86	gold quality
islet of Langerhans	UBERON:0000006	84.53	gold quality
palpebral conjunctiva	UBERON:0001812	84.52	gold quality
right adrenal gland cortex	UBERON:0035827	82.82	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.80	gold quality
right adrenal gland	UBERON:0001233	82.44	gold quality
metanephros	UBERON:0000081	81.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.58	gold quality
left adrenal gland	UBERON:0001234	81.32	gold quality
left adrenal gland cortex	UBERON:0035825	80.77	gold quality
prefrontal cortex	UBERON:0000451	80.74	gold quality
ventricular zone	UBERON:0003053	80.71	gold quality
pancreas	UBERON:0001264	80.68	gold quality
colonic mucosa	UBERON:0000317	80.62	gold quality
adrenal tissue	UBERON:0018303	80.45	gold quality
adrenal gland	UBERON:0002369	80.39	gold quality
kidney epithelium	UBERON:0004819	80.34	silver quality
mucosa of paranasal sinus	UBERON:0005030	80.07	gold quality
adult mammalian kidney	UBERON:0000082	80.05	gold quality
adrenal cortex	UBERON:0001235	80.05	gold quality
mucosa of transverse colon	UBERON:0004991	79.90	gold quality
body of pancreas	UBERON:0001150	79.78	gold quality
stromal cell of endometrium	CL:0002255	79.66	gold quality
hypothalamus	UBERON:0001898	79.39	gold quality
pigmented layer of retina	UBERON:0001782	79.22	gold quality
ganglionic eminence	UBERON:0004023	78.96	gold quality
ileal mucosa	UBERON:0000331	78.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.55	gold quality
endometrium	UBERON:0001295	78.47	gold quality
lower lobe of lung	UBERON:0008949	78.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	221.02
E-ANND-3	no	2.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBXT

miRNA regulators (miRDB)

76 targeting PRMT6, 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-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6779-5P	99.70	65.76	2363

Literature-anchored findings (GeneRIF, showing 40)

• methylates HIV-1 Tat protein and acts as a restriction factor for HIV-1 replication (PMID:15596808)
• severely impairs the function of HIV-1 Rev binding to and export of viral RNA (PMID:17176473)
• findings show HIV-1 Tat is a specific substrate of PRMT6 which targets Tat R52 & R53 residues for arginine methylation; PRMT6 can compromise Tat transcriptional activation & may represent a form of innate cellular immunity in regard to HIV-1 replication (PMID:17267505)
• the arginine methyltransferase PRMT6 catalyses H3R2 di-methylation in vitro and controls global levels of H3R2me2a in vivo (PMID:17898714)
• PRMT6 methylates H3R2 and is a negative regulator of N-terminal H3 tail binding (PMID:18077460)
• findings identify PRMT6 as the mammalian methyltransferase for H3 R2 and establish the enzyme as a crucial negative regulator of H3 K4 trimethylation and transcriptional activation (PMID:18079182)
• TSP-1 is a transcriptional repression target of PRMT6 (PMID:19509293)
• PRMT6 may be involved in human carcinogenesis and may thus be a therapeutic target for various types of cancer. (PMID:20473859)
• In this study, we use Forster resonance energy transfer (FRET) to determine dissociation constant (K(D)) values for dimerization of PRMT1 and PRMT6. (PMID:20812326)
• the molecular mechanisms of PRMT catalysis (PMID:22219200)
• dysregulation of PRMT6-dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile. (PMID:22673335)
• PRMT6 is recruited by RUNX1 and mediates asymmetric histone H3 arginine-2 dimethylation (H3R2me2a) at megakaryocytic genes in progenitor cells. (PMID:22777353)
• Gene expression and promoter analysis show that p21 and p27 are direct targets of PRMT6, which involves methylation of arginine-2 of histone H3. Our findings imply arginine methylation of histones by PRMT6 in cell cycle regulation (PMID:22916108)
• Specific arginine residues of p16 protein are methylated by PRMT6 which may be critical for the activity of p16. (PMID:23032699)
• Findings indicate that expression of PRMT4/CARM1 and PRMT6 is deregulated in melanoma. (PMID:23265702)
• 36 new putative partners for PRMT6 were identified. (PMID:23326497)
• these data demonstrate that PRMT6 overexpression is associated with regulation of motility and invasion through up-regulation of TSP-1 and down-regulation of MMPs in human cancer cells. (PMID:23380452)
• Authors show that PRMT6 requires the activation domain, but surprisingly not the basic domain, of HIV-1 Tat for protein interaction. (PMID:23800116)
• These results show that PRMT6 automethylation plays a role in the stability of this protein and that this event is indispensible for its anti-HIV-1 activity. (PMID:23866860)
• Data show arginine methyltransferase PRMT6 methylates the AT-hook motif of regulatory factor RFX5 and downregulates HLA-DQ expression. (PMID:23911394)
• Arginine 42 of histone H3 (H3R42), is dimethylated by the methyltransferases coactivator arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo. (PMID:23980157)
• PRMT6 specifically interacts with ERalpha at its ligand-binding domain. (PMID:24742914)
• PRMT6 mediates cigarette smoke extract induced apoptosis and inflammation through H3R2me2a in HUVECs. (PMID:25481537)
• TBL1 is required to protect GPS2 from degradation, with methylation of GPS2 by arginine methyltransferase PRMT6 regulating the interaction with TBL1 and inhibiting proteasome-dependent degradation. (PMID:26070566)
• N terminus is methylated by PRMT6 and that this critically affects the functions of pUL69 for efficient mRNA export and replication of human cytomegalovirus. (PMID:26178996)
• PRMT6 methylates tumor cell p21 at arginine 156 and promotes phosphorylation of threonine 145 on p21, increasing the cytoplasmic localization of p21 and inducing resistance to anticancer drugs. (PMID:26436589)
• Data show that HIV-1 Tat methylation by protein arginine methyltransferase 6 (PRMT6) can inhibit nucleolar retention. (PMID:26611710)
• PRMT6, which was down-regulated by androgen receptors and influenced cell migration and apoptosis of germ cells, could play a potentially important role in spermatogenesis. (PMID:26690413)
• PRMT6 influences PRC-mediated gene silencing at the rostral HOXA genes locus. (PMID:26848759)
• Data suggest that histone-arginine N-methyltransferase PRMT6 (PRMT6) plays an oncogenic role in prostate cancer (PCa) and predicts for more clinically aggressive disease, constituting a potential target for patients with Prostate cancer (CRPC). (PMID:27323813)
• Based on the structural information here and available in the PDB database, we proposed a mechanism that can rationalize the distinctive arginine methylation product specificity of different types of arginine methyltransferases and pinpoint the structural determinant of such a specificity (PMID:27480107)
• Our data reveal that PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and open up the possibility that manipulation of PRMT6 activity could facilitate enhanced erythropoiesis for therapeutic use. (PMID:29025910)
• PRMT6 negatively regulates DNA methylation in cancer. PRMT6 overexpression impairs chromatin association of UHRF1, an accessory factor of DNMT1, resulting in passive DNA demethylation. (PMID:29262320)
• This study indicated that the hypomethylation of PRMT6 promoter could be a novel diagnostic biomarker for colorectal cancer. (PMID:29927001)
• Loss of PRMT6 Causes Hepatocellular Carcinoma. (PMID:30332648)
• H3R2me2as is a strong prognostic indicator of gastric cancer (GC) patients, and PRMT6-overexpressing GC cells may acquire invasiveness through direct transcriptional inhibition of PCDH7 by increasing H3R2me2as level. (PMID:30508037)
• PRMT6 is physically associated with PTEN, promotes asymmetrical dimethylation of PTEN, and regulates the PI3K-AKT cascade through PTEN R159 methylation. (PMID:30886105)
• Loss of PPARalpha from the intestine promotes colon carcinogenesis by increasing DNMT1/PRMT6-mediated DNA methylation. (PMID:31154022)
• CRAF Methylation by PRMT6 Regulates Aerobic Glycolysis-Driven Hepatocarcinogenesis via ERK-Dependent PKM2 Nuclear Relocalization and Activation. (PMID:31469916)
• PRMT6 Promotes Lung Tumor Progression via the Alternate Activation of Tumor-Associated Macrophages. (PMID:31619507)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prmt6	ENSDARG00000069706
mus_musculus	Prmt6	ENSMUSG00000049300
rattus_norvegicus	Prmt6	ENSRNOG00000017187
drosophila_melanogaster	Art2	FBGN0031592

Paralogs (7): PRMT8 (ENSG00000111218), PRMT1 (ENSG00000126457), PRMT7 (ENSG00000132600), CARM1 (ENSG00000142453), PRMT2 (ENSG00000160310), PRMT9 (ENSG00000164169), PRMT3 (ENSG00000185238)

Protein

Protein identifiers

Protein arginine N-methyltransferase 6 — Q96LA8 (reviewed: Q96LA8)

Alternative names: Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6, Histone-arginine N-methyltransferase PRMT6

All UniProt accessions (2): Q96LA8, A0A3B3ITK4

UniProt curated annotations — full annotation on UniProt →

Function. Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 ‘Arg-2’ to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 ‘Lys-4’ (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 ‘Arg-3’ (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator. May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC). Methylates GPS2, protecting GPS2 from ubiquitination and degradation. Methylates SIRT7, inhibiting SIRT7 histone deacetylase activity and promoting mitochondria biogenesis.

Subunit / interactions. Interacts with EPB41L3 and NCOA1. Interacts with FBXO24. (Microbial infection) Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC). (Microbial infection) Interacts with human cytomegalovirus protein UL69.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in kidney and testis.

Post-translational modifications. Automethylation enhances its stability and antiretroviral activity. Ubiquitinated by the SCF-FBXO24 E3 ubiquitin ligase, leading to proteasomal degradation.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LA8-1	1	yes
Q96LA8-2	2

RefSeq proteins (1): NP_060607* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025799	Arg_MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR041698	Methyltransf_25	Domain
IPR055135	PRMT_dom	Domain

Pfam: PF13649, PF22528

Enzyme classification (BRENDA):

• EC 2.1.1.319 — type I protein arginine methyltransferase (BRENDA: 13 organisms, 109 substrates, 121 inhibitors, 26 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
[HISTONE H2A]-L-ARGININE	0.0005–0.128	3
[HISTONE H3]-L-ARGININE	0.001–0.0282	3
[HISTONE H4]-L-ARGININE	0.0017–0.0388	3
[GRGGFGGRGGFRGGRGG]-L-ARGININE	0.0003–0.0008	2
[HISTONE H4(1-22) PEPTIDE]-L-ARGININE3	0.0002–0.0008	2
FYSGFNS-DIMETHYL-R8-P-DIMETHYL-R10-GRVYATSWY	0.0222	1
FYSGFNS-DIMETHYL-R8-PRG-DIMETHYL-R12-VYATSWY	0.0007	1
FYSGFNS-DIMETHYL-R8-PRGRVYATSWY	0.0006	1
FYSGFNSRP-DIMETHYL-R10-G-DIMETHYL-R12-VYATSWY	0.008	1
FYSGFNSRP-METHYL-R10-GRVYATSWY	0.0007	1
[HISTONE H4(1-16) PEPTIDE]-L-ARGININE3	0.0003	1
[PABPN1 MUTANT DELTAC20]-L-ARGININE	0.0004	1
[PABPN1 MUTANT DELTAC27]-L-ARGININE	0.0001	1
[PABPN1 MUTANT DELTAC33]-L-ARGININE	—	1
[PABPN1 MUTANT DELTAC40]-L-ARGININE	0.0032	1

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + 2 S-adenosyl-L-methionine = N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:48096)

UniProt features (56 total): strand 17, helix 15, binding site 5, modified residue 4, mutagenesis site 3, turn 3, active site 2, chain 1, domain 1, cross-link 1, splice variant 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
4QQK	X-RAY DIFFRACTION	1.88
6W6D	X-RAY DIFFRACTION	1.91
4HC4	X-RAY DIFFRACTION	1.97
5WCF	X-RAY DIFFRACTION	1.98
6P7I	X-RAY DIFFRACTION	2
5HZM	X-RAY DIFFRACTION	2.02
7NR4	X-RAY DIFFRACTION	2.03
4Y30	X-RAY DIFFRACTION	2.1
5EGS	X-RAY DIFFRACTION	2.15
4Y2H	X-RAY DIFFRACTION	2.37
6WAD	X-RAY DIFFRACTION	2.45
4QPP	X-RAY DIFFRACTION	2.52
5E8R	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LA8-F1	93.80	0.88

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 (2): 155; 164

Ligand- & substrate-binding residues (5): 141; 57; 66; 90; 112

Post-translational modifications (5): 21, 29, 35, 37, 369

Mutagenesis-validated functional residues (3):

Position	Phenotype
35	inhibits automethylation but does not affect methylation of other proteins. reduces protein stability.
86–88	in prmt6dn; abolishes histone methyltransferase h3r2me2a and transcriptional coactivator activities and reduces protein
369	resistant to degradation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1

MSigDB gene sets: 160 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MAZ_Q6, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TAL1ALPHAE47_01, GOBP_CELLULAR_SENESCENCE, CAGCTG_AP4_Q5, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, MODULE_331, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_REGULATION_OF_HEMOPOIESIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), base-excision repair (GO:0006284), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of mitochondrion organization (GO:0010821), methylation (GO:0032259), regulation of megakaryocyte differentiation (GO:0045652), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of cell cycle process (GO:0090068), cellular senescence (GO:0090398), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974), peptidyl-arginine methylation (GO:0018216), cellular response to stress (GO:0033554)

GO Molecular Function (14): chromatin binding (GO:0003682), protein-arginine N-methyltransferase activity (GO:0016274), protein-arginine omega-N monomethyltransferase activity (GO:0035241), protein-arginine omega-N asymmetric methyltransferase activity (GO:0035242), histone methyltransferase activity (GO:0042054), histone binding (GO:0042393), histone H4R3 methyltransferase activity (GO:0044020), histone H3R2 methyltransferase activity (GO:0070611), histone H2AR3 methyltransferase activity (GO:0070612), histone H3 methyltransferase activity (GO:0140938), protein binding (GO:0005515), methyltransferase activity (GO:0008168), obsolete histone arginine N-methyltransferase activity (GO:0008469), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-arginine N-methyltransferase activity	5
DNA-templated transcription	2
cellular response to stress	2
binding	2
protein methyltransferase activity	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA repair	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
mitochondrion organization	1
regulation of organelle organization	1
metabolic process	1
megakaryocyte differentiation	1
regulation of myeloid cell differentiation	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of cell cycle process	1
cell cycle process	1
positive regulation of cell cycle	1
cellular process	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
protein methylation	1
peptidyl-arginine modification	1
response to stress	1
cellular response to stimulus	1
arginine N-methyltransferase activity	1
histone modifying activity	1
protein binding	1
histone H4 methyltransferase activity	1

Protein interactions and networks

STRING

2434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRMT6	PRMT5	O14744	836
PRMT6	MECP2	P51608	824
PRMT6	POLB	P06746	771
PRMT6	WDR5	P61964	696
PRMT6	H3-3A	P06351	690
PRMT6	H3C14	Q71DI3	690
PRMT6	H3-5	Q6NXT2	690
PRMT6	H3C1	P02295	690
PRMT6	H3-4	Q16695	687
PRMT6	H3-7	Q5TEC6	675
PRMT6	DOT1L	Q8TEK3	671
PRMT6	SMYD3	Q9H7B4	655
PRMT6	EHMT2	Q96KQ7	641
PRMT6	HMGA1	P10910	593
PRMT6	SETD1A	O15047	587

IntAct

166 interactions, top by confidence:

A	B	Type	Score
MRPL38	PRMT6	psi-mi:“MI:0915”(physical association)	0.660
LEF1	PRMT6	psi-mi:“MI:0915”(physical association)	0.640
DDX23	PRPF4	psi-mi:“MI:0914”(association)	0.640
PRMT6	HMGA1	psi-mi:“MI:0915”(physical association)	0.630
PRMT6		psi-mi:“MI:0915”(physical association)	0.560
	PRMT6	psi-mi:“MI:0915”(physical association)	0.560
AKT3	HSP90AA1	psi-mi:“MI:0914”(association)	0.560
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CIRBP	PRMT5	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
ILF2	RRP8	psi-mi:“MI:0914”(association)	0.530
ZFC3H1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.530
SPIN4	PRMT6	psi-mi:“MI:0914”(association)	0.530
RBM3	PRMT5	psi-mi:“MI:0914”(association)	0.530
NRM	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
PRMT6	HMGA2	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (225): KIF9 (Two-hybrid), PRMT6 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), TFCP2 (Affinity Capture-MS), UBP1 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), KIRREL (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), ENAH (Affinity Capture-MS), SEC23IP (Affinity Capture-MS), MADD (Affinity Capture-MS), FOXC1 (Affinity Capture-MS), TP73 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B3PEJ0, A0A2K3DU55, A2XFU5, A2XU53, A2YQ58, A4HUY0, A4I1F7, A4RPM5, A8I2V9, B6TN12, B8A031, B8AA76, B8B016, B9FK36, C0PN26, C5XKZ1, C5Y9R0, E1BRE2, E2RDZ6, O43824, P18080, P52506, P52507, P84172, Q0D3F2, Q0J705, Q10MI9, Q2KIF8, Q2KNB4, Q2QMG2, Q3U6U5, Q5AQE4, Q5R6G3, Q5ZAQ2, Q5ZHX9, Q6H4G3, Q6L534, Q6NZB1, Q6Z4A7, Q74ZW4

Diamond homologs: A0A3Q0KHE7, A0A411EW25, A0JMU5, A2AV36, A2Y953, A2YPT7, A2Z0C0, A3KPF2, A6QQV6, A8IEF3, B0JYW5, B0W3L6, B3DLB3, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4JXV2, B4KA23, B4LVS8, B4MNL1, B4NKI9, B4PVH6, B4QVW6, D9IVE5, O13648, O60678, O70467, O82210, P38074, P55345, Q08A71, Q0J2C6, Q174R2, Q28F07, Q29B63, Q3U3W5, Q4AE70, Q54EF2, Q54HI0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRMT6	“down-regulates activity”	SIRT7	methylation
AMPK	“down-regulates activity”	PRMT6	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

22 predictions. Top by Δscore:

Variant	Effect	Δscore
1:107057511:G:GT	donor_gain	0.5500
1:107057838:GAC:G	donor_gain	0.4600
1:107057589:TTCC:T	donor_gain	0.3900
1:107057612:G:T	donor_gain	0.3900
1:107057347:TG:T	donor_gain	0.3600
1:107057481:C:G	donor_gain	0.3300
1:107057448:G:GT	donor_gain	0.3200
1:107057517:G:GT	donor_gain	0.3100
1:107057566:C:CT	acceptor_gain	0.3000
1:107057570:G:GA	acceptor_gain	0.2800
1:107057598:A:AG	donor_gain	0.2700
1:107057579:TGCCA:T	acceptor_gain	0.2500
1:107057587:G:A	acceptor_gain	0.2500
1:107057348:GAAGC:G	donor_gain	0.2300
1:107057349:AAGCA:A	donor_gain	0.2300
1:107057512:A:T	donor_gain	0.2300
1:107057434:G:T	donor_gain	0.2200
1:107057433:G:GT	donor_gain	0.2100
1:107057552:C:G	donor_gain	0.2100
1:107057701:TGC:T	donor_gain	0.2100
1:107057612:G:GT	donor_gain	0.2000
1:107057702:GCA:G	donor_gain	0.2000

AlphaMissense

2402 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:107057589:T:C	F292L	1.000
1:107057591:C:A	F292L	1.000
1:107057591:C:G	F292L	1.000
1:107056894:T:C	M60T	0.999
1:107056895:G:A	M60I	0.999
1:107056895:G:C	M60I	0.999
1:107056895:G:T	M60I	0.999
1:107057181:T:A	W156R	0.999
1:107057181:T:C	W156R	0.999
1:107057667:T:A	W318R	0.999
1:107057667:T:C	W318R	0.999
1:107057669:G:C	W318C	0.999
1:107057669:G:T	W318C	0.999
1:107056902:G:C	D63H	0.998
1:107056903:A:T	D63V	0.998
1:107057004:A:C	S97R	0.998
1:107057006:C:A	S97R	0.998
1:107057006:C:G	S97R	0.998
1:107057014:G:A	C100Y	0.998
1:107057015:T:G	C100W	0.998
1:107057175:A:C	S154R	0.998
1:107057176:G:T	S154I	0.998
1:107057177:C:A	S154R	0.998
1:107057177:C:G	S154R	0.998
1:107057179:A:T	E155V	0.998
1:107057575:G:A	G287D	0.998
1:107056894:T:G	M60R	0.997
1:107056990:G:T	G92V	0.997
1:107057005:G:T	S97I	0.997
1:107057050:A:T	E112V	0.997

dbSNP variants (sampled 300 via entrez): RS1001035384 (1:107056168 C>G), RS1001316129 (1:107056764 G>A), RS1001445088 (1:107056358 CAAAA>C,CAAA,CAAAAA), RS1001910428 (1:107056172 A>C), RS1001954473 (1:107056387 G>A,C), RS1003005629 (1:107058458 T>G), RS1003407749 (1:107058160 A>C), RS1003865990 (1:107056482 G>T), RS1005066427 (1:107058040 G>A), RS1005497758 (1:107059793 C>A,T), RS1005527537 (1:107055183 T>C), RS1005581310 (1:107055490 C>T), RS1006334970 (1:107059374 A>G), RS1006384339 (1:107059632 G>A), RS1006710970 (1:107058234 C>G)

Disease associations

OMIM: gene MIM:608274 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001362_1	Non-obstructive azoospermia	6.000000e-10
GCST001428_18	Intelligence	7.000000e-06
GCST001612_1	Sex hormone-binding globulin levels	2.000000e-07
GCST001612_18	Sex hormone-binding globulin levels	1.000000e-11
GCST001957_13	Obesity (early onset extreme)	9.000000e-06
GCST002250_5	Blood pressure measurement (low sodium intervention)	1.000000e-08
GCST002250_7	Blood pressure measurement (low sodium intervention)	7.000000e-09
GCST005042_1	Restless legs syndrome	3.000000e-63
GCST005834_1	Response to SSRI in MDD or openness	1.000000e-06
GCST008151_29	Waist circumference	4.000000e-06
GCST008152_166	Weight	7.000000e-06
GCST008160_74	Waist circumference	4.000000e-06
GCST010002_364	Refractive error	7.000000e-15
GCST010204_54	Low density lipoprotein cholesterol levels	2.000000e-09
GCST010988_248	Adult body size	3.000000e-08
GCST90013407_150	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-17

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004696	sex hormone-binding globulin measurement
EFO:0005402	response to low sodium diet
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007914	openness measurement
EFO:0004338	body weight
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1275221 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,670 (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
CHEMBL437	SULFATHIAZOLE	4	7,148
CHEMBL1088977	ADEMETIONINE	3	1,522

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.1.1.- Protein arginine N-methyltransferases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
MS023	Inhibition	8.22	pKd
EPZ020411	Inhibition	8.0	pIC50
SGC6870	Inhibition	7.11	pIC50
MS049	Inhibition	7.06	pKd
C21	Inhibition	5.06	pIC50

Binding affinities (BindingDB)

2 measured of 4 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MS023 (Compound 3)	KI	23 nM
N1-Methyl-N1-((4-(3-(trifluoromethyl)phenyl)-1H-pyrrol-3-yl)methyl)ethane-1,2-diamine (Compound 2)	KI	120 nM

ChEMBL bioactivities

198 potent at pChembl≥5 of 236 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	Ki	0.8	nM	CHEMBL3901808
8.92	IC50	1.2	nM	CHEMBL4094513
8.77	IC50	1.7	nM	CHEMBL5559689
8.70	IC50	2	nM	CHEMBL3589043
8.70	IC50	2	nM	CHEMBL3589029
8.62	Ki	2.4	nM	CHEMBL5723346
8.52	IC50	3	nM	CHEMBL3589042
8.52	Ki	3	nM	CHEMBL5722978
8.40	IC50	4	nM	CHEMBL3901808
8.40	IC50	4	nM	CHEMBL5633822
8.33	IC50	4.7	nM	CHEMBL5723346
8.30	IC50	5	nM	CHEMBL3590417
8.22	Kd	6	nM	CHEMBL3901808
8.15	IC50	7	nM	CHEMBL3589026
8.15	IC50	7.1	nM	CHEMBL3589039
8.10	IC50	8	nM	CHEMBL3589030
8.05	IC50	9	nM	CHEMBL5722978
8.00	IC50	10	nM	CHEMBL3589039
8.00	IC50	10	nM	CHEMBL3589031
8.00	IC50	10	nM	CHEMBL3589028
8.00	IC50	10	nM	CHEMBL5562404
8.00	IC50	10	nM	CHEMBL5633815
7.96	IC50	11	nM	CHEMBL3589027
7.96	IC50	11	nM	CHEMBL3589912
7.92	IC50	12	nM	CHEMBL5558087
7.92	IC50	12	nM	CHEMBL3901808
7.89	IC50	13	nM	CHEMBL3589040
7.80	IC50	15.85	nM	CHEMBL4463793
7.80	Ki	16	nM	CHEMBL4463793
7.75	IC50	18	nM	CHEMBL4463793
7.70	IC50	20	nM	CHEMBL3589041
7.64	IC50	23	nM	CHEMBL3589032
7.60	IC50	25	nM	CHEMBL3589033
7.60	IC50	25	nM	CHEMBL3589913
7.60	IC50	25	nM	CHEMBL3956007
7.60	IC50	25	nM	CHEMBL3906680
7.60	IC50	25.12	nM	CHEMBL4544587
7.60	IC50	25	nM	CHEMBL6149812
7.58	IC50	26	nM	CHEMBL3984626
7.57	IC50	27	nM	CHEMBL3957029
7.55	IC50	28	nM	CHEMBL3939593
7.55	IC50	28	nM	CHEMBL4544587
7.52	IC50	30	nM	CHEMBL3970878
7.52	IC50	30	nM	CHEMBL3952337
7.52	IC50	30	nM	CHEMBL5420795
7.52	IC50	30.5	nM	CHEMBL5613785
7.50	IC50	32	nM	CHEMBL3589034
7.47	IC50	34	nM	CHEMBL3961701
7.42	IC50	38	nM	CHEMBL3924657
7.40	IC50	40	nM	CHEMBL3943629

PubChem BioAssay actives

167 with measured affinity, of 439 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’-methyl-N’-[[4-(4-propan-2-yloxyphenyl)-1H-pyrrol-3-yl]methyl]ethane-1,2-diamine	1801573: PRMT Biochemical Assays from Article 10.1021/acschembio.5b00839: “A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases.”	ki	0.0008	uM
N’-[[2-(2-chlorophenyl)sulfanylphenyl]methyl]-N’-methylethane-1,2-diamine	1471460: Inhibition of PRMT6 (unknown origin) incubated for 15 mins followed by substrate addition measured after 60 mins by AlphaLisa method	ic50	0.0012	uM
N’-[[5-[4,4-bis(ethoxymethyl)cyclohexyl]-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	2069868: Inhibition of N-terminal His tagged human recombinant PRMT6 (2 to 375 residues) expressed in Escherichia coli using SAM and Histone (1 to 21 residues) as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by Topcount reader based analysis	ic50	0.0017	uM
N’-methyl-N’-[[5-(4-phenoxyphenyl)-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0020	uM
N,N-dimethyl-3-[4-[5-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-4-yl]phenoxy]benzamide	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0020	uM
N,N-dimethyl-3-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]benzamide	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0030	uM
N’-methyl-N’-[[4-[3-(trifluoromethyl)phenyl]-1H-pyrrol-3-yl]methyl]ethane-1,2-diamine	1801573: PRMT Biochemical Assays from Article 10.1021/acschembio.5b00839: “A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases.”	ki	0.0030	uM
N’-[[4-(4-propan-2-yloxyphenyl)-1H-pyrrol-3-yl]methyl]ethane-1,2-diamine	2138376: Inhibition of PRMT6 (unknown origin)	ic50	0.0040	uM
N-methyl-2-[4-[5-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-4-yl]phenoxy]benzamide	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0050	uM
N’-methyl-N’-[[5-(4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0070	uM
N,N’-dimethyl-N’-[[5-[4-[3-[2-(oxan-4-yl)ethoxy]cyclobutyl]oxyphenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1980608: Inhibition of PRMT6 (unknown origin) by AlphaLISA assay in vitro assay	ic50	0.0071	uM
N’-[[5-(3-chloro-4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]-N’-methylethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0080	uM
N’-methyl-N’-[[5-[4-(2-methylpropyl)phenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0100	uM
N’-[[5-(3-chloro-4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0100	uM
(2S)-1-[[2-[4,4-bis(ethoxymethyl)cyclohexyl]oxyphenyl]methyl-methylamino]-3-(methylamino)propan-2-ol	2069840: Inhibition of PRMT6 (unknown origin) by AlphaLISA assay	ic50	0.0100	uM
N’-[[5-[4-[3-(2-cyclohexylethoxy)cyclobutyl]oxyphenyl]-1H-pyrazol-4-yl]methyl]-N-methylethane-1,2-diamine	2138376: Inhibition of PRMT6 (unknown origin)	ic50	0.0100	uM
N,N’-dimethyl-N’-[[5-(4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0110	uM
N’-[[5-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl]-N’-methylethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0110	uM
N’-[[2-[4,4-bis(methoxymethyl)cyclohexyl]oxyphenyl]methyl]-N,N’-dimethylethane-1,2-diamine;dihydrochloride	2069840: Inhibition of PRMT6 (unknown origin) by AlphaLISA assay	ic50	0.0120	uM
N’-methyl-N’-[[5-[4-(3-morpholin-4-ylpropoxy)phenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0130	uM
N-[3-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrrol-3-yl]phenyl]prop-2-enamide	1549188: Inhibition of human PRMT6 using [3H]SAM as donor and [3H]methylated biotin-labeled peptide as substrate by scintillation proximity assay	ic50	0.0158	uM
1-[4-[4-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrazol-5-yl]phenyl]piperazin-1-yl]-2-phenylethanone	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0200	uM
N’-[[5-(3-chloro-4-propan-2-yloxyphenyl)-1-methylpyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0230	uM
N’-[[5-(4-ethoxyphenyl)-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0250	uM
2-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]butan-1-ol	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0250	uM
2-[4-[(2-bromophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0250	uM
2-[4-[[4-(3,5-dimethylpyrazol-1-yl)phenyl]methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0250	uM
N-[3-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrrol-3-yl]phenyl]propanamide	1549188: Inhibition of human PRMT6 using [3H]SAM as donor and [3H]methylated biotin-labeled peptide as substrate by scintillation proximity assay	ic50	0.0251	uM
2-[4-[[4-(2,3-dichlorophenoxy)phenyl]methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0260	uM
N-methyl-2-[4-[(4-phenylphenyl)methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0270	uM
2-[4-[(4-cyclohexylphenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0280	uM
2-[4-[(2-chlorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0300	uM
N-methyl-2-[4-[(3-phenylphenyl)methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0300	uM
N-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-2-pyridinyl]phenyl]cyclopropanesulfonamide	1980608: Inhibition of PRMT6 (unknown origin) by AlphaLISA assay in vitro assay	ic50	0.0300	uM
2-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethyl]-1-(2-bromophenyl)guanidine	2127551: Inhibition of PRMT6 (unknown origin)	ic50	0.0305	uM
3-methyl-2-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]butan-1-ol	1233971: Inhibition of FLAG and hexa-histidine tagged full-length human PRMT6 expressed in HEK293F cells pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0320	uM
N-methyl-2-(4-phenylmethoxypiperidin-1-yl)ethanamine	1808541: Inhibition of PRMT6 (unknown origin)	ic50	0.0340	uM
2-[4-[(4-fluorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0380	uM
2-[4-[(4-chlorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0400	uM
2-[4-[(4-bromophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0440	uM
N-methyl-2-[4-[[4-(trifluoromethoxy)phenyl]methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0460	uM
2-[4-[(2-fluorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0470	uM
N-methyl-2-[4-[[4-(2,2,2-trifluoroethoxy)phenyl]methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0480	uM
N-methyl-2-[4-[(2-phenylphenyl)methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0480	uM
2-[4-[(3-bromophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0530	uM
N-methyl-2-[4-(2-phenylethyl)piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0560	uM
2-[4-[(3-fluorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0560	uM
N-methyl-2-[4-[[2-(trifluoromethyl)phenyl]methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0640	uM
(2S)-1-[[2-[[3-chloro-4-(1,3-thiazol-2-yl)phenyl]methoxy]phenyl]methyl-methylamino]-3-(methylamino)propan-2-ol	2104091: Inhibition of PRMT6 (unknown origin)	ic50	0.0640	uM
N-methyl-2-[4-[[4-(2-methylbutan-2-yl)phenyl]methoxy]piperidin-1-yl]ethanamine	1319868: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay	ic50	0.0670	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	affects expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Resveratrol	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Berberine	increases expression	1
Cocaine	affects response to substance, decreases reaction, increases expression, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lead	increases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

194 unique, capped per target: 179 binding, 15 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1273736	Binding	Inhibition of His6x-tagged PRMT6-mediated arginine methylation expressed in Escherichia coli BL21 (DE3) using H3(1-31) peptide and [14C]-SAM by scintillation counting	Discovery and mechanistic study of a class of protein arginine methylation inhibitors. — J Med Chem
CHEMBL5445484	Functional	Affinity Phenotypic Cellular interaction: (Western Blot (PRMT6-dependent H4R3 asymmetric di-methylation in HEK293T cells)) EUB0000271b PRMT6	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

5 cell lines: 2 embryonic stem cell, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4CZ	PRMT6-KO-10	Embryonic stem cell	Male
CVCL_A4DA	PRMT6-KO-24	Embryonic stem cell	Male
CVCL_B1BE	Abcam HEK293 PRMT6 KO	Transformed cell line	Female
CVCL_TH14	HAP1 PRMT6 (-) 1	Cancer cell line	Male
CVCL_XR89	HAP1 PRMT6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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