PRMT8

Summary

PRMT8 (protein arginine methyltransferase 8, HGNC:5188) is a protein-coding gene on chromosome 12p13.32, encoding Protein arginine N-methyltransferase 8 (Q9NR22). S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dime….

Arginine methylation is a widespread posttranslational modification mediated by arginine methyltransferases, such as PRMT8. Arginine methylation is involved in a number of cellular processes, including DNA repair, RNA transcription, signal transduction, protein compartmentalization, and possibly protein translation (Lee et al., 2005 [PubMed 16051612]).

Source: NCBI Gene 56341 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 40 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019854

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5188
Approved symbol	PRMT8
Name	protein arginine methyltransferase 8
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111218
Ensembl biotype	protein_coding
OMIM	610086
Entrez	56341

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000261252, ENST00000382622, ENST00000452611, ENST00000543701, ENST00000890277, ENST00000927112, ENST00000927113, ENST00000969655, ENST00000969656

RefSeq mRNA: 2 — MANE Select: NM_019854 NM_001256536, NM_019854

CCDS: CCDS58200, CCDS8521

Canonical transcript exons

ENST00000382622 — 10 exons

Exon	Start	End
ENSE00001492840	3491203	3491700
ENSE00003499445	3583058	3583208
ENSE00003518637	3593099	3593973
ENSE00003524854	3540606	3540791
ENSE00003531979	3576871	3576986
ENSE00003551849	3553651	3553714
ENSE00003585365	3592231	3592352
ENSE00003622627	3569477	3569564
ENSE00003627010	3549936	3550091
ENSE00003651107	3568706	3568848

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 93.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7444 / max 57.4145, expressed in 167 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123492	0.4092	142
123494	0.2210	64
123493	0.0669	46
123491	0.0474	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	93.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.13	gold quality
primary visual cortex	UBERON:0002436	89.18	gold quality
prefrontal cortex	UBERON:0000451	86.78	gold quality
right frontal lobe	UBERON:0002810	85.87	gold quality
nucleus accumbens	UBERON:0001882	85.41	gold quality
frontal cortex	UBERON:0001870	85.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.04	gold quality
neocortex	UBERON:0001950	84.32	gold quality
caudate nucleus	UBERON:0001873	84.25	gold quality
endothelial cell	CL:0000115	83.74	gold quality
superior frontal gyrus	UBERON:0002661	83.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.32	gold quality
occipital lobe	UBERON:0002021	83.27	gold quality
putamen	UBERON:0001874	83.10	gold quality
anterior cingulate cortex	UBERON:0009835	82.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.74	gold quality
cingulate cortex	UBERON:0003027	82.69	gold quality
cerebral cortex	UBERON:0000956	81.58	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.43	gold quality
cerebellar cortex	UBERON:0002129	81.24	gold quality
cerebellar hemisphere	UBERON:0002245	81.23	gold quality
telencephalon	UBERON:0001893	81.18	gold quality
cerebellum	UBERON:0002037	80.71	gold quality
postcentral gyrus	UBERON:0002581	80.27	gold quality
entorhinal cortex	UBERON:0002728	78.99	gold quality
parietal lobe	UBERON:0001872	78.78	gold quality
cortical plate	UBERON:0005343	76.49	gold quality
forebrain	UBERON:0001890	75.97	gold quality
brain	UBERON:0000955	75.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting PRMT8, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4677-5P	99.70	70.09	1940

Literature-anchored findings (GeneRIF, showing 9)

• PRMT8 is an active arginine methyltransferase that is membrane-associated and tissue-specific (PMID:16051612)
• PRMT8 N-terminal domain may function as an autoregulator that may be displaced by interaction with one or more physiological inducers. (PMID:17925405)
• The interaction between PRMT8 and the EWS protein was charcterized. (PMID:18320585)
• EWS is a substrate for PRMT8, as efficient as for PRMT1 (PMID:18698489)
• wild type FUS (FUS-WT) specifically interacts with protein arginine methyltransferases 1 and 8 (PRMT1 and PRMT8) and undergoes asymmetric dimethylation (PMID:23620769)
• Mutational defects in PRMT8 is not the cause of frontotemporal lobar degeneration. (PMID:23635657)
• automethylation of the N terminus likely regulates PRMT8 activity by decreasing the affinity of the enzyme for AdoMet (PMID:23946480)
• Biochemical, biophysical and mutagenesis experiments demonstrated that hPRMT8 forms an octamer in solution. (PMID:26876602)
• PRMT8 in human embryonic stem cells plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation. (PMID:28543863)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	PRMT8	ENSDARG00000040633
danio_rerio	prmt8b	ENSDARG00000045760
mus_musculus	Prmt8	ENSMUSG00000030350
rattus_norvegicus	Prmt8	ENSRNOG00000053804
drosophila_melanogaster	Art1	FBGN0037834
caenorhabditis_elegans		WBGENE00013766

Paralogs (7): PRMT1 (ENSG00000126457), PRMT7 (ENSG00000132600), CARM1 (ENSG00000142453), PRMT2 (ENSG00000160310), PRMT9 (ENSG00000164169), PRMT3 (ENSG00000185238), PRMT6 (ENSG00000198890)

Protein

Protein identifiers

Protein arginine N-methyltransferase 8 — Q9NR22 (reviewed: Q9NR22)

Alternative names: Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4

All UniProt accessions (1): Q9NR22

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dimer. Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.

Subunit / interactions. Homodimer. Tetramer; individual homodimers associates to form a homotetramer. Homooctamer; individual homodimers associates to form a homooctamer and homooligomerization is required for proper localization to the cell membrane. Heterodimer with PRMT1; heterodimerization may recruit PRMT1 activity to the plasma membrane. Interacts with PRMT2 (via the SH3 domain). Interacts with FYN (via the SH3 domain). Interacts with EWS; independently of EWS methylation status.

Subcellular location. Cell membrane.

Tissue specificity. Brain-specific.

Domain organisation. The SH3-binding motifs mediate the interaction with SH3 domain-containing proteins such as PRMT2 and FYN, possibly leading to displace the N-terminal domain and activate the protein. The N-terminal region (1-60) inhibits the arginine N-methyltransferase activity.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT8 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR22-1	1	yes
Q9NR22-2	2

RefSeq proteins (2): NP_001243465, NP_062828* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF06325, 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), 2 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)
• L-arginyl-[protein] + S-adenosyl-L-methionine = N(omega)-methyl-L-arginyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:48100)

UniProt features (60 total): strand 18, helix 11, mutagenesis site 7, binding site 6, turn 4, modified residue 2, short sequence motif 2, active site 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, splice variant 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5DST	X-RAY DIFFRACTION	2.96
4X41	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR22-F1	86.66	0.79

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): 185; 194

Ligand- & substrate-binding residues (6): 95; 119–122; 119; 141; 170; 86

Post-translational modifications (3): 58, 73, 2

Mutagenesis-validated functional residues (7):

Position	Phenotype
2	loss of cell membrane localization.
273	no effect on homodimerization but decreased homooligomerization; when associated with a-295 and a-349.
295	no effect on homodimerization but decreased homooligomerization; when associated with a-273 and a-349.
303	decreases homooligomerization and cell membrane localization. no effect on homodimerization, s-adenosyl-l-methionine bin
345	no effect on homooligomerization. no effect on s-adenosyl-l-methionine binding and ews protein methylation. no effect on
349	no effect on homodimerization but decreased homooligomerization; when associated with a-273 and a-295.
382	no effect on homooligomerization. no effect on s-adenosyl-l-methionine binding and ews protein methylation. no effect on

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GGTGTGT_MIR329, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOMF_SULFUR_COMPOUND_BINDING, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, GOMF_N_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY

GO Biological Process (7): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), protein methylation (GO:0006479), peptidyl-arginine methylation (GO:0018216), protein homooligomerization (GO:0051260), regulation of modification of postsynaptic actin cytoskeleton (GO:1905274), methylation (GO:0032259)

GO Molecular Function (13): S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), enzyme binding (GO:0019899), protein-arginine omega-N monomethyltransferase activity (GO:0035241), protein-arginine omega-N asymmetric methyltransferase activity (GO:0035242), histone methyltransferase activity (GO:0042054), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone H4 methyltransferase activity (GO:0140939), S-adenosyl-L-methionine binding (GO:1904047), protein binding (GO:0005515), methyltransferase activity (GO:0008168), protein-arginine N-methyltransferase activity (GO:0016274), transferase activity (GO:0016740)

GO Cellular Component (3): plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
protein-arginine N-methyltransferase activity	2
protein methyltransferase activity	2
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein alkylation	1
macromolecule methylation	1
protein methylation	1
peptidyl-arginine modification	1
protein complex oligomerization	1
modification of postsynaptic actin cytoskeleton	1
regulation of modification of postsynaptic structure	1
metabolic process	1
methyltransferase activity	1
histone modifying activity	1
identical protein binding	1
protein dimerization activity	1
histone methyltransferase activity	1
cation binding	1
sulfur compound binding	1
binding	1
transferase activity, transferring one-carbon groups	1
arginine N-methyltransferase activity	1
catalytic activity	1
membrane	1
cell periphery	1
plasma membrane	1
cytoplasmic side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRMT8	PRMT5	O14744	811
PRMT8	FBL	P22087	700
PRMT8	H4C7	Q99525	665
PRMT8	PRMT7	Q9NVM4	663
PRMT8	H4C16	P02304	662
PRMT8	SMYD3	Q9H7B4	655
PRMT8	SETD7	Q8WTS6	642
PRMT8	WDR77	Q9BQA1	522
PRMT8	PRMT2	P55345	485
PRMT8	CARM1	Q86X55	476
PRMT8	KMT5B	Q4FZB7	469
PRMT8	KMT5C	Q86Y97	468
PRMT8	SUV39H2	Q9H5I1	458
PRMT8	DOT1L	Q8TEK3	453
PRMT8	TDRD3	Q9H7E2	450

IntAct

68 interactions, top by confidence:

A	B	Type	Score
SYNCRIP	PRMT8	psi-mi:“MI:0915”(physical association)	0.830
PRMT8	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.830
PRMT8	SYNCRIP	psi-mi:“MI:0914”(association)	0.830
PRMT8	PRMT8	psi-mi:“MI:0915”(physical association)	0.820
PRMT8	PRMT1	psi-mi:“MI:0915”(physical association)	0.720
PRMT1	PRMT8	psi-mi:“MI:0915”(physical association)	0.720
PRMT1	PRMT8	psi-mi:“MI:0915”(physical association)	0.630
PRMT8	PRMT1	psi-mi:“MI:0915”(physical association)	0.630
KRTAP6-3	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
SYNCRIP	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
TNPO2	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
UBL5	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
NCAPG	ARRDC1	psi-mi:“MI:0914”(association)	0.560
RSRC1	JMJD6	psi-mi:“MI:0914”(association)	0.550
GIMAP2	TOR1B	psi-mi:“MI:0914”(association)	0.530
RNF26	NME2P1	psi-mi:“MI:0914”(association)	0.530
APOL2	BPNT1	psi-mi:“MI:0914”(association)	0.530
ERAL1	COL1A1	psi-mi:“MI:0914”(association)	0.530
PRMT8	SERPINH1	psi-mi:“MI:0915”(physical association)	0.400
SUCNR1	PRMT8	psi-mi:“MI:0915”(physical association)	0.400
ATAD1	PRMT8	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (165): PRMT8 (Two-hybrid), PRMT8 (Two-hybrid), PRMT8 (Two-hybrid), EWSR1 (Affinity Capture-MS), NEFM (Affinity Capture-MS), VIM (Affinity Capture-MS), INA (Affinity Capture-MS), HNRNPU (Affinity Capture-MS), FAM120A (Affinity Capture-MS), DHX9 (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), PRMT1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A2AV36, A2Y8B9, A2Z0C0, A2Z8S0, A4IG42, A4QP75, A6QQV6, A7YW45, B0JYW5, B0X4N1, B3DLB3, B3M1E1, B3MF31, B3NP10, B3P4N5, B4GA28, B4GZ20, B4HJC0, B4I8G2, B4P925, B4PVH6, B4QI55, B4QVW6, B5DZN7, D9IVE5, Q0J2C6, Q16NS8, Q29B63, Q3U3W5, Q5RGQ2, Q5U4E8, Q5VS72, Q5ZIB9, Q6NTR1, Q6NUA1, Q6P2P2, Q6PAK3, Q6PCI6, Q75G68

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2637 predictions. Top by Δscore:

Variant	Effect	Δscore
12:3540787:ACGAG:A	donor_loss	1.0000
12:3540789:GAGG:G	donor_loss	1.0000
12:3540791:GGTA:G	donor_loss	1.0000
12:3540792:GTAA:G	donor_loss	1.0000
12:3540793:T:G	donor_loss	1.0000
12:3549929:A:AG	acceptor_gain	1.0000
12:3549930:T:G	acceptor_gain	1.0000
12:3549932:ACAG:A	acceptor_gain	1.0000
12:3549934:A:AG	acceptor_gain	1.0000
12:3549934:A:AT	acceptor_loss	1.0000
12:3549934:AG:A	acceptor_gain	1.0000
12:3549935:G:A	acceptor_loss	1.0000
12:3549935:G:GT	acceptor_gain	1.0000
12:3549935:GG:G	acceptor_gain	1.0000
12:3549935:GGA:G	acceptor_gain	1.0000
12:3549935:GGAA:G	acceptor_gain	1.0000
12:3549935:GGAAA:G	acceptor_gain	1.0000
12:3550008:G:GT	donor_gain	1.0000
12:3550014:GTG:G	donor_gain	1.0000
12:3552613:A:T	donor_gain	1.0000
12:3553715:G:GG	donor_gain	1.0000
12:3567146:GAA:G	donor_gain	1.0000
12:3568845:GCTG:G	donor_gain	1.0000
12:3568846:CTGG:C	donor_loss	1.0000
12:3568847:TGGT:T	donor_loss	1.0000
12:3568848:GGTAA:G	donor_loss	1.0000
12:3568849:GTAA:G	donor_loss	1.0000
12:3568850:T:TC	donor_loss	1.0000
12:3569563:CT:C	donor_gain	1.0000
12:3569565:G:GG	donor_gain	1.0000

AlphaMissense

2640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:3540768:T:C	Y80H	1.000
12:3540786:C:G	H86D	1.000
12:3549940:T:A	M89K	1.000
12:3549940:T:C	M89T	1.000
12:3549940:T:G	M89R	1.000
12:3549941:G:A	M89I	1.000
12:3549941:G:C	M89I	1.000
12:3549941:G:T	M89I	1.000
12:3549943:T:A	L90Q	1.000
12:3549943:T:C	L90P	1.000
12:3549948:G:C	D92H	1.000
12:3549949:A:C	D92A	1.000
12:3549949:A:T	D92V	1.000
12:3549950:T:A	D92E	1.000
12:3549950:T:G	D92E	1.000
12:3549969:T:C	Y99H	1.000
12:3549969:T:G	Y99D	1.000
12:3549973:G:C	R100P	1.000
12:3550018:T:A	V115E	1.000
12:3550021:T:C	L116P	1.000
12:3550029:G:A	G119R	1.000
12:3550029:G:C	G119R	1.000
12:3550029:G:T	G119W	1.000
12:3550030:G:A	G119E	1.000
12:3550035:G:C	G121R	1.000
12:3550036:G:A	G121D	1.000
12:3550036:G:T	G121V	1.000
12:3550041:G:A	G123R	1.000
12:3550041:G:C	G123R	1.000
12:3550041:G:T	G123W	1.000

dbSNP variants (sampled 300 via entrez): RS1000015512 (12:3422536 C>T), RS1000042673 (12:3410474 G>A), RS1000064796 (12:3452602 C>G,T), RS1000073160 (12:3479140 G>A,C,T), RS1000075805 (12:3540911 C>T), RS1000088830 (12:3422222 C>A), RS1000100952 (12:3461442 C>T), RS1000117740 (12:3416097 G>C), RS1000131264 (12:3574071 C>G), RS1000139269 (12:3554972 C>T), RS1000157527 (12:3467686 A>G), RS1000188995 (12:3514263 T>C), RS1000195664 (12:3457433 T>A), RS1000248907 (12:3520719 G>A,C), RS1000249662 (12:3546618 C>T)

Disease associations

OMIM: gene MIM:610086 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000288_10	HDL cholesterol	8.000000e-16
GCST003875_9	Gut microbiota (bacterial taxa)	1.000000e-08
GCST006218_101	Erosive tooth wear (severe vs non-severe)	3.000000e-06
GCST006226_3	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST008310_9	Cardiac Troponin-T levels	4.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0005043	cardiac troponin T measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3108648 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,522 (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
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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
MS023	Inhibition	8.89	pKi
MS049	Inhibition	5.8	pIC50

Binding affinities (BindingDB)

2 measured of 5 human assays (5 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

72 potent at pChembl≥5 of 82 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	IC50	1.1	nM	CHEMBL4094513
8.89	Ki	1.3	nM	CHEMBL3901808
8.77	IC50	1.7	nM	CHEMBL5559689
8.70	IC50	2	nM	CHEMBL3589029
8.70	Ki	2	nM	CHEMBL5723346
8.41	IC50	3.9	nM	CHEMBL5723346
8.40	IC50	4	nM	CHEMBL3901808
8.30	IC50	5	nM	CHEMBL3901808
8.30	IC50	5	nM	CHEMBL5633822
8.15	IC50	7	nM	CHEMBL3589030
8.00	IC50	10	nM	CHEMBL3589031
8.00	IC50	10	nM	CHEMBL3589028
8.00	IC50	10	nM	CHEMBL3589026
7.85	IC50	14	nM	CHEMBL3589027
7.77	Ki	17	nM	CHEMBL5722978
7.68	IC50	21	nM	CHEMBL3589037
7.66	IC50	22	nM	CHEMBL3589033
7.66	IC50	22	nM	CHEMBL3589032
7.64	IC50	23	nM	CHEMBL3589036
7.62	IC50	24	nM	CHEMBL5558087
7.55	IC50	28	nM	CHEMBL3589913
7.51	IC50	31	nM	CHEMBL5562404
7.49	IC50	32.1	nM	CHEMBL5613785
7.38	IC50	42	nM	CHEMBL5722978
7.36	IC50	44	nM	CHEMBL3589038
7.26	IC50	55	nM	CHEMBL3589034
7.19	IC50	65	nM	CHEMBL3590417
7.17	IC50	67	nM	CHEMBL3589912
7.16	IC50	70	nM	CHEMBL3589035
7.14	IC50	73	nM	CHEMBL5566004
6.96	IC50	110	nM	CHEMBL4463793
6.89	IC50	130	nM	CHEMBL4544587
6.75	IC50	179	nM	CHEMBL3589042
6.65	IC50	223	nM	CHEMBL3589039
6.65	IC50	223	nM	CHEMBL5633815
6.46	IC50	347	nM	CHEMBL3589043
6.45	IC50	352	nM	CHEMBL5431366
6.35	IC50	450	nM	CHEMBL3589040
6.24	IC50	573	nM	CHEMBL3970878
6.12	IC50	759	nM	ADEMETIONINE
6.04	IC50	920	nM	CHEMBL5266562
5.85	IC50	1410	nM	CHEMBL5191769
5.82	IC50	1500	nM	CHEMBL3589041
5.82	Ki	1500	nM	CHEMBL5722993
5.80	IC50	1600	nM	CHEMBL3961701
5.76	IC50	1740	nM	CHEMBL3409550
5.73	IC50	1850	nM	CHEMBL3955728
5.71	IC50	1950	nM	CHEMBL5173678
5.71	IC50	1970	nM	CHEMBL5396270
5.68	IC50	2100	nM	CHEMBL3780926

PubChem BioAssay actives

68 with measured affinity, of 279 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’-[[2-(2-chlorophenyl)sulfanylphenyl]methyl]-N’-methylethane-1,2-diamine	1471461: Inhibition of PRMT8 (unknown origin) incubated for 15 mins followed by substrate addition measured after 60 mins by AlphaLisa method	ic50	0.0011	uM
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	0.0013	uM
N’-[[5-[4,4-bis(ethoxymethyl)cyclohexyl]-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	2069869: Inhibition of PRMT8 (unknown origin) 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	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0020	uM
N’-[[4-(4-propan-2-yloxyphenyl)-1H-pyrrol-3-yl]methyl]ethane-1,2-diamine	2138377: Inhibition of PRMT8 (unknown origin)	ic50	0.0050	uM
N’-[[5-(3-chloro-4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]-N’-methylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0070	uM
N’-methyl-N’-[[5-[4-(2-methylpropyl)phenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) 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	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0100	uM
N’-methyl-N’-[[5-(4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0100	uM
N,N’-dimethyl-N’-[[5-(4-propan-2-yloxyphenyl)-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0140	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	0.0170	uM
N’-[[5-[3-(2-cyclohexylethoxy)-5-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0210	uM
N’-[[5-(3-chloro-4-propan-2-yloxyphenyl)-1-methylpyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0220	uM
2-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]butan-1-ol	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0220	uM
N,N’-dimethyl-N’-[[5-[3-(2-phenylethoxy)-5-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0230	uM
N’-[[2-[4,4-bis(methoxymethyl)cyclohexyl]oxyphenyl]methyl]-N,N’-dimethylethane-1,2-diamine;dihydrochloride	2069841: Inhibition of PRMT8 (unknown origin) by AlphaLISA assay	ic50	0.0240	uM
N’-[[5-(4-ethoxyphenyl)-1H-pyrazol-4-yl]methyl]-N,N’-dimethylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0280	uM
(2S)-1-[[2-[4,4-bis(ethoxymethyl)cyclohexyl]oxyphenyl]methyl-methylamino]-3-(methylamino)propan-2-ol	2069841: Inhibition of PRMT8 (unknown origin) by AlphaLISA assay	ic50	0.0310	uM
2-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethyl]-1-(2-bromophenyl)guanidine	2127586: Inhibition of PRMT8 (unknown origin)	ic50	0.0321	uM
4-methyl-2-[3-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenoxy]pentan-1-ol	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0440	uM
3-methyl-2-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]butan-1-ol	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0550	uM
N-methyl-2-[4-[5-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-4-yl]phenoxy]benzamide	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0650	uM
N’-[[5-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl]-N’-methylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0670	uM
N’-[[4-[3-chloro-4-propan-2-yloxy-5-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl]methyl]-N’-methylethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.0700	uM
(2S)-1-[[2-[[3-chloro-4-(1,3-thiazol-2-yl)phenyl]methoxy]phenyl]methyl-methylamino]-3-(methylamino)propan-2-ol	2104092: Inhibition of PRMT8 (unknown origin)	ic50	0.0730	uM
N-[3-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrrol-3-yl]phenyl]prop-2-enamide	1549202: Inhibition of human PRMT8 using [3H]SAM as donor and [3H]methylated biotin-labeled peptide as substrate by scintillation proximity assay	ic50	0.1100	uM
N-[3-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrrol-3-yl]phenyl]propanamide	1549202: Inhibition of human PRMT8 using [3H]SAM as donor and [3H]methylated biotin-labeled peptide as substrate by scintillation proximity assay	ic50	0.1300	uM
N,N-dimethyl-3-[4-[4-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-5-yl]phenoxy]benzamide	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.1790	uM
N’-[[5-[4-[3-(2-cyclohexylethoxy)cyclobutyl]oxyphenyl]-1H-pyrazol-4-yl]methyl]-N-methylethane-1,2-diamine	2138377: Inhibition of PRMT8 (unknown origin)	ic50	0.2230	uM
N,N’-dimethyl-N’-[[5-[4-[3-[2-(oxan-4-yl)ethoxy]cyclobutyl]oxyphenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.2230	uM
N,N-dimethyl-3-[4-[5-[[methyl-[2-(methylamino)ethyl]amino]methyl]-1H-pyrazol-4-yl]phenoxy]benzamide	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.3470	uM
N-[4-[5-[[methyl-[2-(methylamino)ethyl]amino]methyl]-3-pyridinyl]phenyl]cyclopropanesulfonamide	1980610: Inhibition of PRMT8 (unknown origin) by AlphaLISA assay in vitro assay	ic50	0.3520	uM
N’-methyl-N’-[[5-[4-(3-morpholin-4-ylpropoxy)phenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	0.4500	uM
N-methyl-2-[4-[(3-phenylphenyl)methoxy]piperidin-1-yl]ethanamine	1319874: Inhibition of PRMT8 (unknown origin) assessed as inhibition of methylation activity measured after 3 hrs using [3H]-SAM by scintillation proximity assay	ic50	0.5730	uM
N’-[[3-[4-anilino-6-(3,5-dimethyl-1,2-oxazol-4-yl)-5-methylpyrimidin-2-yl]phenyl]methyl]-N-methylethane-1,2-diamine	1934159: Inhibition of PRMT8 (unknown origin) incubated for 15 mins measured after 60 min by AlphaLISA assay	ic50	0.9200	uM
methyl 6-[4-[[N’-[3-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]propyl]carbamimidoyl]amino]butylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	1.4100	uM
1-[4-[4-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrazol-5-yl]phenyl]piperazin-1-yl]-2-phenylethanone	1233972: Inhibition of N-terminal GST tagged full-length human PRMT8 expressed in Escherichia coli (BL21(DE3) pre-incubated for 30 mins before addition of a [3H]SAM and peptide mix	ic50	1.5000	uM
N’-methyl-N’-[[5-[3-(trifluoromethyl)phenyl]triazolidin-4-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	1.5000	uM
N’-methyl-N’-[[5-[3-(trifluoromethyl)phenyl]-2H-triazol-4-yl]methyl]ethane-1,2-diamine	2197562: Binding affinity to human PRMT8 assessed as inhibition constant using (3H) methylated biotin labelled peptide as substrate in presence of 3H-SAM by scintillation proximity assay	ki	1.5000	uM
N-methyl-2-(4-phenylmethoxypiperidin-1-yl)ethanamine	1319874: Inhibition of PRMT8 (unknown origin) assessed as inhibition of methylation activity measured after 3 hrs using [3H]-SAM by scintillation proximity assay	ic50	1.6000	uM
(2E)-2-[(E)-3-[1,1-dimethyl-3-(3-phenylpropyl)benzo[e]indol-3-ium-2-yl]prop-2-enylidene]-1,1-dimethyl-3-(3-phenylpropyl)benzo[e]indole bromide	1196393: Displacement of [3H]-SAM from recombinant His6-tagged PRMT8 (unknown origin) expressed in Escherichia coli BL21(DE3) incubated for 5 mins prior to H4(1 to 20)-BTN peptide addition measured after 8 mins by scintillation proximity assay	ic50	1.7400	uM
2-[4-[(3-fluorophenyl)methoxy]piperidin-1-yl]-N-methylethanamine	1319874: Inhibition of PRMT8 (unknown origin) assessed as inhibition of methylation activity measured after 3 hrs using [3H]-SAM by scintillation proximity assay	ic50	1.8500	uM
methyl 6-[4-[[N’-[(E)-3-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]prop-2-enyl]carbamimidoyl]amino]butylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	1.9500	uM
methyl 6-[3-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]propylcarbamoylamino]-4-hydroxy-8-(trifluoromethyl)naphthalene-2-carboxylate	2012351: Inhibition of N-terminal/C-terminal His-tagged human recombinant full-length PRMT8 (61 to 394 residues) using histone H4 as substrate and 3H-SAM as cosubstrate incubated for 60 mins by scintillation counter analysis	ic50	1.9700	uM
2-(4-benzylpiperidin-1-yl)ethanamine	1286873: Inhibition of human PRMT8 using 24 residues of biotin labelled histone4 substrate and tritiated 3H-S-adenosylmethionine by scintillation proximity assay	ic50	2.1000	uM
(2R)-1-(methylamino)-3-[5-[[4-(1,3-thiazol-2-yl)phenyl]methoxy]-3,4-dihydro-1H-isoquinolin-2-yl]propan-2-ol	1599068: Inhibition of PRMT8 (unknown origin) preincubated for 15 mins followed by substrate addition and measured after 60 mins by AlphaLisa assay	ic50	3.7000	uM
methyl 7-[6-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]hexylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	3.8200	uM
methyl 6-[7-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]heptylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	5.8400	uM
methyl 6-[5-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]pentylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	5.8700	uM
methyl 6-[4-[[amino-[2-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]ethylamino]methylidene]amino]butylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	1883075: Inhibition of human full length recombinant his-tagged PRMT8 (61 to 394 residues) using histone H4 as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay	ic50	6.0000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	decreases expression, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
aflatoxin B2	increases methylation, decreases methylation	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Berberine	increases expression	1
Copper	decreases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1
Ribavirin	decreases expression	1
Rotenone	decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

99 unique, capped per target: 94 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3111896	Binding	Inhibition of PRMT8 (unknown origin)-mediated incorporation of methyl group from [3H]-SAM into peptide substrate up to 50 uM by scintillation proximity assay	Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. — ACS Med Chem Lett
CHEMBL5444956	Functional	Affinity Phenotypic Cellular interaction: (Western Blot (inhibitor of H4R3 methylation in MCF-7 cells)) EUB0000261b PRMT8	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

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