PRMT5

Summary

PRMT5 (protein arginine methyltransferase 5, HGNC:10894) is a protein-coding gene on chromosome 14q11.2, encoding Protein arginine N-methyltransferase 5 (O14744). Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. It is a common-essential gene (DepMap: required in 94.9% of cancer cell lines).

This gene encodes an enzyme that belongs to the methyltransferase family. The encoded protein catalyzes the transfer of methyl groups to the amino acid arginine, in target proteins that include histones, transcriptional elongation factors and the tumor suppressor p53. This gene plays a role in several cellular processes, including transcriptional regulation, and the assembly of small nuclear ribonucleoproteins. A pseudogene of this gene has been defined on chromosome 4. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 10419 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 57 total
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 8 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug; 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 94.9% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.27 (highly constrained)
• MANE Select transcript: NM_006109
• Interaction hub: 3,046 STRING partners (top 2% of genes corpus-wide)
• Notable: 57 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10894
Approved symbol	PRMT5
Name	protein arginine methyltransferase 5
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SKB1Hs
Ensembl gene	ENSG00000100462
Ensembl biotype	protein_coding
OMIM	604045
Entrez	10419

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 25 protein_coding, 7 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 4 retained_intron

MANE Select: ENST00000324366

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 8, TSL 3: 10, TSL 4: 4, TSL 5: 4

ENST00000324366, ENST00000216350, ENST00000397440, ENST00000397441, ENST00000421938, ENST00000454731, ENST00000476175, ENST00000553417, ENST00000553502, ENST00000553550, ENST00000553641, ENST00000553787, ENST00000553897, ENST00000553915, ENST00000554716, ENST00000554867, ENST00000554910, ENST00000555454, ENST00000555530, ENST00000556032, ENST00000556043, ENST00000556426, ENST00000556616, ENST00000557015, ENST00000557415, ENST00000557443, ENST00000557758, ENST00000627278, ENST00000903535, ENST00000903536, ENST00000948386, ENST00001054678, ENST00001054679, ENST00001066093, ENST00001066094, ENST00001066095, ENST00001066096, ENST00001110139, ENST00001112746, ENST00001140069

RefSeq mRNA: 6 — MANE Select: NM_006109 NM_001039619, NM_001282953, NM_001282954, NM_001282955, NM_001282956, NM_006109

CCDS: CCDS41922, CCDS61394, CCDS61395, CCDS61396, CCDS9579

Canonical transcript exons

ENST00000324366 — 17 exons

Exon	Start	End
ENSE00002438513	22920529	22921056
ENSE00002524725	22929252	22929376
ENSE00003480646	22928126	22928211
ENSE00003485706	22928497	22928615
ENSE00003490969	22926506	22926555
ENSE00003493346	22924270	22924392
ENSE00003504639	22922176	22922240
ENSE00003506566	22927526	22927660
ENSE00003512765	22922742	22922835
ENSE00003567613	22923051	22923160
ENSE00003580528	22924008	22924183
ENSE00003588053	22922443	22922559
ENSE00003616383	22924632	22924709
ENSE00003629689	22926133	22926296
ENSE00003649944	22924479	22924537
ENSE00003665575	22926702	22926814
ENSE00003672945	22924879	22925040

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6296 / max 155.4802, expressed in 1800 samples.

Highest expression (Bgee): ventricular zone, amniotic fluid, ganglionic eminence, embryo, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRMT5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.4e-60	+0.38	14:22922704:T:C
Whole Blood	sqtl	2.1e-26	+0.51	14:22949515:C:T
Spleen	sqtl	2.4e-04	+0.57	14:22960979:C:T
Artery Tibial	eqtl	4.3e-03	-0.17	14:22901383:T:TTA
Adipose Subcutaneous	eqtl	7.9e-03	-0.36	14:22907337:G:A
Brain Putamen basal ganglia	eqtl	1.2e-02	-0.55	14:22768452:G:C
Brain Hypothalamus	eqtl	2.8e-02	+1.60	14:22551975:CTG:C
Spleen	eqtl	3.4e-02	-0.21	14:23008384:G:A
Testis	eqtl	3.4e-02	-0.19	14:22929623:G:A
Adrenal Gland	eqtl	4.6e-02	+0.49	14:22259195:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
142268	24.3493	1800
142267	0.1505	64
142266	0.1299	55

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.95	gold quality
amniotic fluid	UBERON:0000173	96.22	gold quality
ganglionic eminence	UBERON:0004023	95.67	gold quality
embryo	UBERON:0000922	95.52	gold quality
lower esophagus mucosa	UBERON:0035834	95.39	gold quality
cortical plate	UBERON:0005343	95.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.97	gold quality
right uterine tube	UBERON:0001302	94.90	gold quality
left ovary	UBERON:0002119	94.60	gold quality
right ovary	UBERON:0002118	94.57	gold quality
esophagus mucosa	UBERON:0002469	94.51	gold quality
gastrocnemius	UBERON:0001388	94.43	gold quality
mucosa of transverse colon	UBERON:0004991	94.39	gold quality
islet of Langerhans	UBERON:0000006	94.31	gold quality
left uterine tube	UBERON:0001303	94.29	gold quality
muscle of leg	UBERON:0001383	94.17	gold quality
right testis	UBERON:0004534	94.04	gold quality
stromal cell of endometrium	CL:0002255	94.00	gold quality
right lobe of thyroid gland	UBERON:0001119	94.00	gold quality
ovary	UBERON:0000992	93.93	gold quality
left testis	UBERON:0004533	93.84	gold quality
esophagus	UBERON:0001043	93.70	gold quality
left lobe of thyroid gland	UBERON:0001120	93.66	gold quality
rectum	UBERON:0001052	93.65	gold quality
body of uterus	UBERON:0009853	93.63	gold quality
body of pancreas	UBERON:0001150	93.51	gold quality
ectocervix	UBERON:0012249	93.36	gold quality
right adrenal gland	UBERON:0001233	93.20	gold quality
thyroid gland	UBERON:0002046	93.16	gold quality
testis	UBERON:0000473	93.07	gold quality
metanephros cortex	UBERON:0010533	93.01	gold quality
left adrenal gland cortex	UBERON:0035825	92.93	gold quality
right adrenal gland cortex	UBERON:0035827	92.90	gold quality
left adrenal gland	UBERON:0001234	92.89	gold quality
tibial nerve	UBERON:0001323	92.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.80	gold quality
lower esophagus	UBERON:0013473	92.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.77	gold quality
endocervix	UBERON:0000458	92.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.69	gold quality
transverse colon	UBERON:0001157	92.62	gold quality
colonic epithelium	UBERON:0000397	92.55	gold quality
body of stomach	UBERON:0001161	92.55	gold quality
adenohypophysis	UBERON:0002196	92.53	gold quality
pancreas	UBERON:0001264	92.52	gold quality
heart left ventricle	UBERON:0002084	92.45	gold quality
skin of abdomen	UBERON:0001416	92.38	gold quality
skin of leg	UBERON:0001511	92.35	gold quality
calcaneal tendon	UBERON:0003701	92.35	gold quality
minor salivary gland	UBERON:0001830	92.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.29	gold quality
adrenal gland	UBERON:0002369	92.19	gold quality
cardiac ventricle	UBERON:0002082	92.15	gold quality
muscle organ	UBERON:0001630	91.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.91	gold quality
vagina	UBERON:0000996	91.90	gold quality
right atrium auricular region	UBERON:0006631	91.89	gold quality
left coronary artery	UBERON:0001626	91.79	gold quality
right frontal lobe	UBERON:0002810	91.79	gold quality
adrenal cortex	UBERON:0001235	91.75	gold quality
cartilage tissue	UBERON:0002418	91.72	gold quality
stomach	UBERON:0000945	91.69	gold quality
right coronary artery	UBERON:0001625	91.67	gold quality
prefrontal cortex	UBERON:0000451	91.65	gold quality
popliteal artery	UBERON:0002250	91.63	gold quality
tibial artery	UBERON:0007610	91.63	gold quality
mouth mucosa	UBERON:0003729	91.62	gold quality
heart	UBERON:0000948	91.55	gold quality
apex of heart	UBERON:0002098	91.55	gold quality
cerebellar hemisphere	UBERON:0002245	91.55	gold quality
pituitary gland	UBERON:0000007	91.48	gold quality
cerebellar cortex	UBERON:0002129	91.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.37	gold quality
prostate gland	UBERON:0002367	91.35	gold quality
oocyte	CL:0000023	91.33	gold quality
adult mammalian kidney	UBERON:0000082	91.30	gold quality
aorta	UBERON:0000947	91.30	gold quality
descending thoracic aorta	UBERON:0002345	91.21	gold quality
colon	UBERON:0001155	91.18	gold quality
coronary artery	UBERON:0001621	91.17	gold quality
cardiac atrium	UBERON:0002081	91.17	gold quality
upper lobe of left lung	UBERON:0008952	91.12	gold quality
saliva-secreting gland	UBERON:0001044	91.09	gold quality
thoracic aorta	UBERON:0001515	91.05	gold quality
adrenal tissue	UBERON:0018303	91.05	gold quality
ascending aorta	UBERON:0001496	91.00	gold quality
zone of skin	UBERON:0000014	90.98	gold quality
omental fat pad	UBERON:0010414	90.98	gold quality
peritoneum	UBERON:0002358	90.97	gold quality
large intestine	UBERON:0000059	90.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.94	gold quality
anterior cingulate cortex	UBERON:0009835	90.81	gold quality
female reproductive system	UBERON:0000474	90.74	gold quality
cingulate cortex	UBERON:0003027	90.72	gold quality
mucosa of stomach	UBERON:0001199	90.68	gold quality
intestine	UBERON:0000160	90.53	gold quality
tendon	UBERON:0000043	90.50	gold quality
secondary oocyte	CL:0000655	90.47	gold quality
right lobe of liver	UBERON:0001114	90.44	gold quality
upper lobe of lung	UBERON:0008948	90.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	45.9
Parathyroid gland	tissue	44.4	medium
Ovary	tissue	42.8	medium
Skeletal muscle	tissue	42.3	low
Fallopian tube	tissue	41.9	high
Frontal cortex	tissue	40.7
Esophagus	tissue	39.7	medium
Tongue	tissue	39.4
Choroid plexus	tissue	37.2
Hippocampal formation	tissue	37.2
Cerebral cortex	tissue	37.1	medium
Somatosensory cortex	tissue	37.1
Colon	tissue	35.9	high
Putamen	tissue	35.6
Basal ganglia	tissue	35.5	medium
Thyroid gland	tissue	35.4	medium
Kidney	tissue	34.5	medium
Motor cortex	tissue	34.0
Prefrontal cortex	tissue	33.6
Rectum	tissue	33.4	high
Smooth muscle	tissue	33.1	not detected
Occipital cortex	tissue	32.9
Vagina	tissue	32.8	low
Breast	tissue	32.6	not detected
Skin 1	tissue	32.5	low
Retrosplenial and cingulate cortex	tissue	32.5
Temporal cortex	tissue	32.4
Septum	tissue	32.3
Tonsil	tissue	32.1	high
Ventral forebrain	tissue	32.1
Locus coeruleus	tissue	31.7
Entorhinal cortex	tissue	31.7
Endometrium 1	tissue	31.5	medium
Thalamus	tissue	31.5
Seminal vesicle	tissue	31.4	medium
Retrosplenial cortex	tissue	31.2
Midbrain	tissue	30.9
Thymus	tissue	30.9
Insular cortex	tissue	30.4
Pons	tissue	30.1
Hypothalamus	tissue	30.1
Nucleus accumbens	tissue	29.8
Substantia nigra	tissue	29.8
Urinary bladder	tissue	29.3	high
Superior colliculi	tissue	29.3
Periaqueductal gray	tissue	29.1
Epididymis	tissue	28.9	high
Medulla oblongata	tissue	28.9
Spinal cord	tissue	28.9
Placenta	tissue	28.8	medium
Retina	tissue	28.5
Testis	tissue	28.3	medium
Amygdala	tissue	28.2
Olfactory bulb	tissue	27.7
Corpus callosum	tissue	27.5
Cervix	tissue	27.3	low
Postcentral gyrus	tissue	27.1
Appendix	tissue	26.3	medium
Prostate	tissue	26.2	high
Cerebellum	tissue	26.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral hippocampus (37.2), Dorsal hippocampus (36.9), Subiculum (33.5), Median raphe nucleus (32.0), Corpus callosum, genu (white matter) (31.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
SMAD7

Upstream regulators (CollecTRI, top): KMT2B, SMARCA1

miRNA regulators (miRDB)

Targeting PRMT5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-4268	94.45	64.09	819

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.272, missense Z 4.52 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000324366 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:22,920,907–22,924,935	219 / 433.6	0.51	no
14:22,924,936–22,928,568	215 / 301.1	0.71	no
14:22,928,569–22,928,610	1 / 19.5	0.05	yes (p 2.9e-05)
14:22,928,611–22,929,361	51 / 53.8	0.95	no
DepMap (CRISPR cell-line fitness): dependent in 94.9% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HUP-T4 (-3.342), HCC38 (-2.37), SNU-840 (-2.367), OCI-LY-19 (-2.266), MCF-7 (-2.177), EFM-19 (-2.168), TE-10 (-2.055), DAN-G (-2.045), S-117 (-2.001), PK-45H (-2.001), KE-37 (-1.965), NB-4 (-1.954), JURL-MK1 (-1.938), TOV-112D (-1.931), HCC1187 (-1.922).

Literature-anchored findings (GeneRIF, showing 40)

• Data show that PRMT5 can be found in association with hSWI/SNF complexes and is involved in regulating the expression of carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase. (PMID:14559996)
• suppressor of tumorigenicity 7 (ST7) and nonmetastatic 23 (NM23) are direct targets of PRMT5-containing BRG1 and hBRM complexes (PMID:15485929)
• It was found that is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression. (PMID:15654770)
• found that FCP1 is a genuine substrate of PRMT5-methylation both in vivo and in vitro, and FCP1-associated PRMT5 can methylate histones H4 in vitro (PMID:15670829)
• Up-regulation of SKB1 is associated with gastric cancer (PMID:15701830)
• contrast to PRMT3, DAL-1/4.1B was found to mediate PRMT5 by either inhibiting (Sm proteins) or enhancing (myelin basic protein) protein methylation. (PMID:15737618)
• Lsm10 and Lsm11, which replace the Sm proteins D1 and D2 in the histone RNA processing U7 snRNPs, associate with pICln in vitro and in vivo without receiving sDMA modifications and with PRMT5 and SMN complexes (PMID:16087681)
• SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A (PMID:16712789)
• results suggest distinct functions of the nuclear and the p44/protein arginine methyltransferase 5 complexes in the developing fetal testis and in the oncogenesis of testicular tumors. (PMID:17437848)
• aberrant expression of PRMT5 leads to altered epigenetic modification of chromatin, which in turn impacts transcriptional performance of anti-cancer genes and growth of transformed lymphoid cells (PMID:17627275)
• that in human cells, PRMT5 and PRMT7 are required for Sm protein sDMA modification, and that Sm protein symmetric dimethylarginine modification is required for snRNP biogenesis in human cells. (PMID:17709427)
• identification of the protein arginine methyltransferase 5 (PRMT5) as an effector recruited to SNAIL through an interaction with AJUBA that functions to repress the SNAIL target gene, E-cadherin (PMID:18347060)
• These results indicate that PRMT5 overexpression epigenetically alters the transcription of key tumor suppressor genes. (PMID:18694959)
• BLIMP1 and PRMT5 were expressed and arginine dimethylation of histones H2A and H4 was detected in human male gonocytes and intratubular germ cell neoplasia unclassified and most seminomas, while downregulated in embryonal carcinoma. (PMID:18992153)
• These results indicate that Ski complexes serve to maintain a TGF-beta-responsive promoter at a repressed basal level via the activities of histone deacetylase and histone arginine methyltransferase. (PMID:19032343)
• FGF-2 is a new substrate of PRMT5. (PMID:19086919)
• Loss of the H4 arginine 3 methylation mark through short hairpin RNA-mediated knockdown of PRMT5 leads to reduced DNMT3A binding, loss of DNA methylation and gene activation. (PMID:19234465)
• ZNF224 recruits the arginine methyltransferase PRMT5 on the transcriptional repressor complex of the aldolase A gene (PMID:19741270)
• The protein arginine methyltransferase 5 (PRMT5) localizes to the GA and forms complexes with several components involved in GA ribbon formation and vesicle tethering. (PMID:20421892)
• PRMT5 induces multiprotein repressor complex containing the histone modifying enzymes SUV4-20h1, casein kinase 2alpha in silencing fetal globin gene expression resulting in beta-thalassemia and sickle cell disease. (PMID:20495075)
• Increased PRMT5 activity mediates key events associated with cyclin D1-dependent neoplastic growth, including CUL4 repression, CDT1 overexpression, and DNA rereplication. (PMID:20951943)
• RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. (PMID:21081503)
• loss of Prmt5 function is early embryonic-lethal due to the abrogation of pluripotent cells in blastocysts (PMID:21159818)
• The activity of SHP is also increased by posttranslational methylation at Arg-57 by protein arginine methyltransferase 5 (PRMT5). (PMID:21262773)
• results indicate that phosphorylation of PRMT5 contributes to the mutant JAK2-induced myeloproliferative phenotype (PMID:21316606)
• COX2-dependent and independent activation of CK2alpha-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival (PMID:21592330)
• results reveal a new cofactor for PDCD4 that alters its tumor suppressor functions and point to the utility of PDCD4/PRMT5 status as both a prognostic biomarker and a potential target for chemotherapy (PMID:21700716)
• Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. (PMID:21917714)
• The results not only provide insight into the molecular mechanisms by which PRMT5 contributes to growth control, but also justify therapeutic targeting of PRMT5. (PMID:21975038)
• analysis of structural insights into protein arginine symmetric dimethylation by PRMT5 (PMID:22143770)
• PRMT5 inhibits the PKCdelta- or 12-O-tetradecanoylphorbol-13-acetate-dependent increase in human involucrin expression, and PRMT5 dimethylates proteins in the p38delta complex. (PMID:22199349)
• Here the authors report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. (PMID:22231400)
• PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation. (PMID:22266372)
• HOXA9 is required for TNF-alpha-dependent binding of PRMT5 to the E-selectin promoter in endothelial cells. (PMID:22269951)
• Data suggest that PRMT5 is highly expressed in lung cancer cells; PRMT5 expression is not detectable in benign lung tissues. Silencing PRMT5 expression strongly inhibits proliferation of lung adenocarcinoma cells in culture and in a xenograft model. (PMID:22708516)
• Protein arginine methyltransferase 5 is a potential oncoprotein that upregulates G1 cyclins/cyclin-dependent kinases and the phosphoinositide 3-kinase/AKT signaling cascade. (PMID:22726390)
• These results imply a novel mechanism by which PRMT5 controls cell growth and contributes to prostate tumorigenesis. (PMID:22952863)
• structure of the surprising hetero-octameric complex reveals the close interaction between the seven-bladed beta-propeller MEP50 and the N-terminal domain of PRMT5, and delineates the structural elements of substrate recognition. (PMID:23071334)
• type II protein arginine methyltransferase 5 has a role in the regulation of Circadian Per1 and CRY1 genes (PMID:23133559)
• PRMT5 triggers the symmetric dimethylation of EBNA2 RG domain to coordinate with EBNA2-mediated transcription. (PMID:23261437)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prmt5	ENSDARG00000079605
mus_musculus	Prmt5	ENSMUSG00000023110
rattus_norvegicus	Prmt5	ENSRNOG00000012046
drosophila_melanogaster	csul	FBGN0015925
caenorhabditis_elegans		WBGENE00016408

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1351645) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 33 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vertebrae morphology	1
scoliosis	1
abnormal chondrocyte morphology	1
tremors	1
decreased brain size	1
abnormal lateral ventricle morphology	1
abnormal cerebellum external granule cell layer morphology	1
decreased body size	1
impaired balance	1
decreased embryo size	1
decreased brain weight	1
akinesia	1
increased neuron apoptosis	1
delayed endochondral bone ossification	1
pallor	1
embryonic growth retardation	1
abnormal intervertebral disk morphology	1
abnormal embryonic/fetal subventricular zone morphology	1
small vertebrae	1
abnormal neuronal precursor proliferation	1
abnormal vertebral body development	1
abnormal intervertebral disk development	1
thin cerebral cortex	1
abnormal endochondral bone ossification	1
abnormal cortical plate morphology	1

+8 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2X0Q3	99.8%	Diamond
Oryza sativa Japonica Group	Q6YXZ7	99.8%	Diamond
Macaca fascicularis	Q4R5M3	99.7%	Diamond
Pongo abelii	Q5R698	99.5%	Diamond
Bos taurus	A7YW45	99.2%	Diamond
Xenopus laevis	Q6NUA1	84.4%	Diamond
Arabidopsis thaliana	Q8GWT4	71.4%	Diamond
Dictyostelium discoideum	Q54KI3	47.7%	Diamond
Schizosaccharomyces pombe 972h-	P78963	38.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRMT5-AS1	ncRNA	100505758
MIR4707	ncRNA	100616424
PRMT5-DT	ncRNA	101926933
HAUS4	protein-coding	54930
AJUBA	protein-coding	84962
TRR-ACG1-3	tRNA	100189243
REM2	protein-coding	161253
RBM23	protein-coding	55147
AJUBA-DT	ncRNA	107984660
C14orf93	protein-coding	60686
LRP10	protein-coding	26020
MMP14	protein-coding	4323

Protein

Protein identifiers

Protein arginine N-methyltransferase 5 — O14744 (reviewed: O14744)

Alternative names: 72 kDa ICln-binding protein, Histone-arginine N-methyltransferase PRMT5, Jak-binding protein 1, Shk1 kinase-binding protein 1 homolog

All UniProt accessions (15): C9JSX3, O14744, G3V2F5, G3V2L6, G3V2X6, G3V3A3, G3V507, G3V580, G3V5L5, G3V5T6, H0YJ77, H0YJD3, H0YJX6, H0YJY6, H7BZ44

UniProt curated annotations — full annotation on UniProt →

Function. Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Methylates SUPT5H and may regulate its transcriptional elongation properties. May methylate the N-terminal region of MBD2. Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 ‘Arg-3’ during germ cell development. Methylates histone H3 ‘Arg-8’, which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage. Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR ‘Tyr-1197’ phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter. Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression. Symmetrically methylates NCL. Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity. Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6.

Subunit / interactions. Forms, at least, homodimers and homotetramers. Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A. Found in a complex composed of PRMT5, WDR77 and RIOK1. RIOK1 and CLNS1A associate with PRMT5 in a mutually exclusive fashion, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively. Interacts with PRDM1. Identified in a complex composed of methylosome and PRMT1 and ERH. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2. Found in a complex with COPRS, RUNX1 and CBFB. Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1. Interacts with EPB41L3; this modulates methylation of target proteins. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1. Interacts with LSM11, PRMT7 and SNRPD3. Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln. Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10. Interacts with WDR77. Interacts with IWS1. Interacts with CRY1. Interacts with POLR2A. Interacts with SMN1/SMN2. Interacts with LYAR; this interaction is direct. Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53. Interacts with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP dependent. Interacts with FAM47E; the interaction is direct, promotes PRMT5 localization to chromatin, and does not disrupt its association with WDR77 or STUB1. Interacts with TDRD6. Interacts with STUB1. Interacts with MBD2. Does not interact with MBD3.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Golgi apparatus.

Tissue specificity. Ubiquitous.

Activity regulation. Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.

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

Isoforms (5)

UniProt ID	Names	Canonical?
O14744-1	1	yes
O14744-2	2
O14744-4	4
O14744-5	5
O14744-3	3

RefSeq proteins (6): NP_001034708, NP_001269882, NP_001269883, NP_001269884, NP_001269885, NP_006100* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007857	Arg_MeTrfase_PRMT5	Family
IPR025799	Arg_MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR035075	PRMT5	Domain
IPR035247	PRMT5_TIM	Domain
IPR035248	PRMT5_C	Domain

Pfam: PF05185, PF17285, PF17286

Enzyme classification (BRENDA)

• EC 2.1.1.320 — type II protein arginine methyltransferase (BRENDA: 10 organisms, 87 substrates, 243 inhibitors, 6 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	—	3
[HISTONE H4 PEPTIDE]-L-ARGININE	0.0042–0.0102	2
[HISTONE H4(1-21)]-L-ARGININE	0.002	1

Catalyzed reactions (Rhea)

• L-arginyl-[protein] + 2 S-adenosyl-L-methionine = N(omega),N(omega)’-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:48108)

UniProt features (106 total): helix 39, strand 33, binding site 7, turn 7, sequence conflict 4, splice variant 3, region of interest 3, chain 2, mutagenesis site 2, active site 2, initiator methionine 1, site 1, modified residue 1, domain 1

Structure

Experimental structures (PDB)

showing 30 of 94 structures by resolution:

PDB	Title	Method	Resolution (Å)
9ZL3	Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 18	X-RAY DIFFRACTION	1.71
9MGQ	Crystal structure of PRMT5:MEP50 in complex with sinefungin and compound 47	X-RAY DIFFRACTION	1.85
6V0P	PRMT5 complex bound to covalent PBM inhibitor BRD6711	X-RAY DIFFRACTION	1.88
7ZVU	HUMAN PRMT5:MEP50 Crystal Structure With MTA and Fragment Bound	X-RAY DIFFRACTION	1.95
9ZL4	Crystal structure of PRMT5:MEP50 in complex with MTA and TNG456	X-RAY DIFFRACTION	1.95
7ZUY	HUMAN PRMT5:MEP50 Crystal Structure With MTA and Fragment Bound	X-RAY DIFFRACTION	2
7S0U	PRMT5/MEP50 crystal structure with MTA and phthalazinone fragment bound	X-RAY DIFFRACTION	2.01
7ZUP	Human PRMT5:MEP50 structure with Fragment (Example 18) and MTA Bound	X-RAY DIFFRACTION	2.01
7ZV2	HUMAN PRMT5:MEP50 Crystal Structure With MTA and Fragment Bound	X-RAY DIFFRACTION	2.01
8VEO	Crystal structure of PRMT5:MEP50 in complex with MTA	X-RAY DIFFRACTION	2.03
4GQB	Crystal Structure of the human PRMT5:MEP50 Complex	X-RAY DIFFRACTION	2.06
9MGR	Crystal structure of PRMT5:MEP50 in complex with MTA and compound 51	X-RAY DIFFRACTION	2.07
7ZUU	HUMAN PRMT5:MEP50 Crystal Structure With MTA and Fragment Bound	X-RAY DIFFRACTION	2.09
7S1R	PRMT5/MEP50 crystal structure with MTA and a phthalazinone inhibitor bound (compound …	X-RAY DIFFRACTION	2.1
6V0N	PRMT5 bound to PBM peptide from Riok1	X-RAY DIFFRACTION	2.11
7SER	PRMT5/MEP50 with compound 30 bound	X-RAY DIFFRACTION	2.14
9EYV	Human PRMT5 in complex with AZ compound 12	X-RAY DIFFRACTION	2.15
9T43	Human PRMT5:MEP50 in complex with AZD3470	X-RAY DIFFRACTION	2.18
9EYX	Human PRMT5 in complex with AZ compound 28	X-RAY DIFFRACTION	2.2
9PCA	HUMAN PRMT5:MEP50 COMPLEX IN COMPLEX WITH LIGAND 18	X-RAY DIFFRACTION	2.2
7S1P	PRMT5/MEP50 crystal structure with sinefungin bound	X-RAY DIFFRACTION	2.21
6RLL	CRYSTAL STRUCTURE OF THE HUMAN PRMT5:MEP50 COMPLEX with JNJ44064146	X-RAY DIFFRACTION	2.22
9MGL	Crystal structure of PRMT5:MEP50 in complex with MTA and GSK3326595	X-RAY DIFFRACTION	2.25
9MGM	Crystal structure of PRMT5:MEP50 in complex with MTA and compound 24	X-RAY DIFFRACTION	2.25
9MRE	From DNA-Encoded Library Screening to AM-9747 - an MTA-Cooperative PRMT5 Inhibitor with …	X-RAY DIFFRACTION	2.25
5EMJ	Crystal structure of PRMT5:MEP50 with Compound 8 and sinefungin	X-RAY DIFFRACTION	2.27
9EYW	Human PRMT5 in complex with AZ compound 21	X-RAY DIFFRACTION	2.3
5FA5	Crystal Structure of PRMT5:MEP50 in complex with MTA and H4 peptide	X-RAY DIFFRACTION	2.34
4X60	Crystal structure of PRMT5:MEP50 with EPZ015666 and sinefungin	X-RAY DIFFRACTION	2.35
9EYU	Human PRMT5 in complex with AZ compound 1	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14744-F1	93.68	0.89

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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 (3)

Position	Role
327	critical for specifying symmetric addition of methyl groups
435	proton donor/acceptor
444	proton donor/acceptor

Ligand- & substrate-binding residues (7)

Position	Role
327	a protein
333–334	S-adenosyl-L-methionine
392	S-adenosyl-L-methionine
419–420	S-adenosyl-L-methionine
435	a protein
444	a protein
324	S-adenosyl-L-methionine

Post-translational modifications (1)

Type	Positions
N-acetylalanine	2

Mutagenesis-validated functional residues (2)

Position	Phenotype
365–369	increased mapk1/mapk3 phosphorylation in response to egf.
367–368	abolishes enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-3214858	RMTs methylate histone arginines	curated
R-HSA-6804760	Regulation of TP53 Activity through Methylation	curated
R-HSA-191859	snRNP Assembly	curated
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-194441	Metabolism of non-coding RNA	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 340 (showing top): GOBP_CIRCADIAN_RHYTHM, PID_HDAC_CLASSI_PATHWAY, GOBP_RIBOSOME_BIOGENESIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, NKX25_02, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (25): spliceosomal snRNP assembly (GO:0000387), chromatin remodeling (GO:0006338), DNA-templated transcription termination (GO:0006353), regulation of DNA-templated transcription (GO:0006355), regulation of mitotic nuclear division (GO:0007088), peptidyl-arginine methylation (GO:0018216), circadian regulation of gene expression (GO:0032922), peptidyl-arginine N-methylation (GO:0035246), endothelial cell activation (GO:0042118), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), negative regulation of cell differentiation (GO:0045596), positive regulation of mRNA splicing, via spliceosome (GO:0048026), positive regulation of oligodendrocyte differentiation (GO:0048714), regulation of ERK1 and ERK2 cascade (GO:0070372), Golgi ribbon formation (GO:0090161), liver regeneration (GO:0097421), regulation of signal transduction by p53 class mediator (GO:1901796), positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway (GO:1904992), positive regulation of rRNA processing (GO:2000234), chromatin organization (GO:0006325), protein methylation (GO:0006479), regulation of gene expression (GO:0010468), methylation (GO:0032259), negative regulation of DNA-templated transcription (GO:0045892), rhythmic process (GO:0048511)

GO Molecular Function (17): p53 binding (GO:0002039), transcription corepressor activity (GO:0003714), methyltransferase activity (GO:0008168), methyl-CpG binding (GO:0008327), protein-arginine N-methyltransferase activity (GO:0016274), protein-arginine omega-N symmetric methyltransferase activity (GO:0035243), histone methyltransferase activity (GO:0042054), identical protein binding (GO:0042802), ribonucleoprotein complex binding (GO:0043021), histone H4R3 methyltransferase activity (GO:0044020), protein heterodimerization activity (GO:0046982), E-box binding (GO:0070888), histone H3 methyltransferase activity (GO:0140938), protein binding (GO:0005515), protein methyltransferase activity (GO:0008276), transferase activity (GO:0016740), protein-containing complex binding (GO:0044877)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), methylosome (GO:0034709), histone methyltransferase complex (GO:0035097), chromosome (GO:0005694), protein-containing complex (GO:0032991)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Metabolism of non-coding RNA	1
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
Metabolism of RNA	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

showing 60 of 72 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
mRNA splicing, via spliceosome	2
DNA-templated transcription	2
regulation of gene expression	2
protein binding	2
protein methyltransferase activity	2
protein-arginine N-methyltransferase activity	2
binding	2
intracellular membrane-bounded organelle	2
methyltransferase complex	2
protein-RNA complex assembly	1
chromatin organization	1
RNA biosynthetic process	1
regulation of RNA biosynthetic process	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
protein methylation	1
peptidyl-arginine modification	1
circadian rhythm	1
peptidyl-arginine methylation	1
cell activation	1
negative regulation of gene expression, epigenetic	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
positive regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
Golgi organization	1
liver development	1
animal organ regeneration	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1
positive regulation of dopamine receptor signaling pathway	1
regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway	1
rRNA processing	1
positive regulation of RNA metabolic process	1
regulation of rRNA processing	1
cellular component organization	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
transferase activity, transferring one-carbon groups	1
nucleotide binding	1
sequence-specific DNA binding	1
arginine N-methyltransferase activity	1
histone modifying activity	1
protein-containing complex binding	1
histone H4 methyltransferase activity	1
protein dimerization activity	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 52 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
DNA-templated transcription termination	BP	mutant phenotype
Golgi ribbon formation	BP	mutant phenotype
chromatin remodeling	BP	direct assay
endothelial cell activation	BP	mutant phenotype
peptidyl-arginine N-methylation	BP	direct assay
peptidyl-arginine methylation	BP	mutant phenotype
positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway	BP	genetic interaction
spliceosomal snRNP assembly	BP	mutant phenotype
Golgi apparatus	CC	direct assay
chromatin	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
histone methyltransferase complex	CC	direct assay
methylosome	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
histone H4R3 methyltransferase activity	MF	direct assay
identical protein binding	MF	physical interaction
methyl-CpG binding	MF	direct assay
methyltransferase activity	MF	direct assay
p53 binding	MF	physical interaction
protein heterodimerization activity	MF	direct assay
protein-arginine N-methyltransferase activity	MF	direct assay
protein-arginine omega-N symmetric methyltransferase activity	MF	direct assay
ribonucleoprotein complex binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,046 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRMT5	WDR77	Q9BQA1	979
PRMT5	PRMT7	Q9NVM4	961
PRMT5	PRMT1	Q99873	915
PRMT5	SNRPD3	P43331	900
PRMT5	TET1	Q8NFU7	886
PRMT5	CLNS1A	P54105	881
PRMT5	TET3	O43151	874
PRMT5	PRMT6	Q96LA8	844
PRMT5	PRMT3	O60678	818
PRMT5	TET2	Q6N021	810
PRMT5	PRMT8	Q9NR22	792
PRMT5	MTAP	Q13126	783
PRMT5	AKT1	P31749	770
PRMT5	H4C7	Q99525	760
PRMT5	H4C16	P02304	757

IntAct

Human interaction partners of PRMT5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 123 partners by confidence:

Partner	Interaction type	MIscore	Records
WDR77	physical association	0.960	9
CLNS1A	association	0.830	6
COPRS	association	0.770	8
H4C16	physical association	0.760	6
RIOK1	association	0.710	5
GRB2	physical association	0.670	3
SNRPB	physical association	0.670	3
E2F1	physical association	0.650	8
YWHAZ	physical association	0.650	3
RBM23	physical association	0.630	3
SRGAP2	physical association	0.610	4
DNMT3A	direct interaction	0.600	4
SMN1	association	0.600	2
CTDP1	physical association	0.590	3
POLR2A	association	0.560	6
AGT	physical association	0.560	3
AIRIM	physical association	0.560	3
BRK1	physical association	0.560	3
CACNB2	physical association	0.560	3
CCT2	physical association	0.560	3
CDC37	physical association	0.560	3
COMT	physical association	0.560	3
EHHADH	physical association	0.560	3
EIF4A3	physical association	0.560	3
ELOA	physical association	0.560	3
EPHB6	physical association	0.560	3
FOS	physical association	0.560	3
GAS8	physical association	0.560	3
HSF1	physical association	0.560	3
KANK2	physical association	0.560	3

BioGRID (817 interactions; top human partners by supporting records in a sample of 600 records): WDR77 (Co-fractionation; 28 records), CLNS1A (Two-hybrid; 17 records), RIOK1 (Affinity Capture-MS; 12 records), STUB1 (Affinity Capture-MS; 7 records), COPRS (Two-hybrid; 6 records), DUSP14 (Affinity Capture-MS; 6 records), PHF1 (Affinity Capture-MS; 6 records), RBFOX2 (Affinity Capture-MS; 6 records), BCL6 (Affinity Capture-Western; 5 records), CUL4B (Affinity Capture-MS; 5 records), FAM47E (Two-hybrid; 4 records), GAR1 (Affinity Capture-MS; 4 records), HIST1H4A (Biochemical Activity; 4 records), MXI1 (Affinity Capture-Western; 4 records), RNF4 (Affinity Capture-Western; 4 records)

SIGNOR signaling

showing 4 of 5 signaling interactions:

A	Effect	B	Mechanism
JAK2	down-regulates	PRMT5	phosphorylation
PRMT5	“up-regulates activity”	HOXA9	methylation
SRC	“down-regulates activity”	PRMT5	phosphorylation
STK11	“up-regulates activity”	PRMT5	phosphorylation

Protein complexes (CORUM) (25)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

25 complexes by size:

Complex	Subunits	Members
★ BRM-SIN3A complex	15	RBBP4, SMARCA2, SMARCB1, SMARCC2, SMARCD1, ACTL6A, HDAC1, HDAC2, PRMT5, SIN3A, SMARCD3, ARID1A, SMARCC1, SMARCD2, SMARCE1
★ BRG1-SIN3A complex	14	SMARCD1, SMARCD2, SMARCD3, ARID1A, RBBP4, SIN3A, SMARCA4, SMARCB1, SMARCE1, ACTL6A, HDAC2, PRMT5, SMARCC1, SMARCC2
★ BRM-SIN3A-HDAC complex	12	SMARCE1, ACTL6A, PRMT5, SMARCC2, SMARCD1, ARID1A, HDAC2, SIN3A, SMARCA2, SMARCB1, SMARCC1, SMARCD2
BRD7-SWI–SNF complex	11	ACTL6A, ARID1A, PRMT5, SMARCC1, SMARCC2, SMARCD1, BRD7, PHF10, SMARCA2, SMARCA4, SMARCE1
★ BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I	11	SMARCE1, ACTL6A, PRMT5, SIN3A, SMARCA4, SMARCC2, ARID1A, HDAC2, SMARCB1, SMARCC1, SMARCD1
BRM-associated complex	10	ACTL6A, ARID1A, SMARCA2, SMARCD1, SMARCD2, SMARCE1, PRMT5, SMARCB1, SMARCC1, SMARCC2
Brm-associated complex	9	ACTL6A, ARID1A, PRMT5, SMARCC1, SMARCC2, SMARCE1, SMARCA2, SMARCB1, SMARCD1
BRG1-associated complex	9	ACTL6A, ARID1A, PRMT5, SMARCD1, SMARCA4, SMARCB1, SMARCC1, SMARCC2, SMARCE1
Brg1-associated complex II	7	ACTL6A, ARID1A, PRMT5, SMARCA4, SMARCB1, SMARCC1, SMARCC2
BRD7-CBP-SWI–SNF complex	7	PRMT5, SMARCA2, SMARCA4, SMARCE1, BRD7, PAG1, PHF10
FCP1-associated protein complex	7	POLR2B, PRMT5, STK38, WDR77, CTDP1, ERH, GTF2F1
Anti-Sm protein complex	7	DDX20, GEMIN2, GEMIN4, PRMT5, SMN1, SNRPB, CLNS1A
★ FIB-associated protein complex	6	PRMT1, PRMT5, TUBA1A, TUBB1, C1QBP, FBL
20S methylosome and RG-containing Sm protein complex	6	SNRPD1, SNRPD2, SNRPD3, CLNS1A, PRMT5, SNRPB
CHTOP-ERH-PRMT1-PRMT5-WDR77 complex	5	PRMT5, WDR77, CHTOP, ERH, PRMT1
COPRS-PRMT5-RUNX1-CBFB complex	4	CBFB, COPRS, PRMT5, RUNX1
20S methylosome-SmD complex	4	CLNS1A, PRMT5, SNRPD1, SNRPD3
★ AR-CLNS1A-PRMT5-WDR77 complex	4	CLNS1A, PRMT5, WDR77, AR
MEP50-PRMT5-ICLN complex	3	CLNS1A, PRMT5, WDR77
AJUBA-PRMT5-SNAI1 complex	3	SNAI1, AJUBA, PRMT5
JBP1-pICln complex	3	CLNS1A, PRMT5, SNRPB
COPRS-PRMT5 complex	2	COPRS, PRMT5
CAPG-PRMT5 complex	2	CAPG, PRMT5
20S methyltransferase core complex	2	CLNS1A, PRMT5
PRMT5 complex	1	PRMT5

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
Metabolism of non-coding RNA	6	43.8×	4e-07
Abortive elongation of HIV-1 transcript in the absence of Tat	5	28.5×	3e-05
MicroRNA (miRNA) biogenesis	5	26.2×	3e-05
Pausing and recovery of Tat-mediated HIV elongation	6	25.4×	8e-06
Tat-mediated HIV elongation arrest and recovery	6	25.4×	8e-06
HIV elongation arrest and recovery	6	23.9×	9e-06
Pausing and recovery of HIV elongation	6	23.9×	9e-06
Formation of the Early Elongation Complex	5	19.3×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	8	40.8×	1e-08
U2-type prespliceosome assembly	5	27.4×	2e-04
positive regulation of mRNA splicing, via spliceosome	5	23.8×	3e-04
regulation of circadian rhythm	5	11.4×	6e-03
RNA splicing	14	10.8×	2e-08
mRNA splicing, via spliceosome	12	9.6×	1e-06
mRNA processing	9	6.2×	2e-03

Disease & clinical

Genetic variants

Variant evidence for PRMT5: 57 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,001):

Position(s)	Effect	Δscore	Sites
14:22922441–22922442	donor_loss	1.0000	5
14:22922740–22922741	donor_loss	1.0000	3
14:22922836–22922837	acceptor_loss	1.0000	6
14:22922841	acceptor_gain	1.0000
14:22922847	acceptor_gain	1.0000
14:22924006–22924007	donor_loss	1.0000	4
14:22924268	donor_loss	1.0000
14:22924393	acceptor_gain	1.0000
14:22924477–22924478	donor_loss	1.0000	5
14:22924538–22924539	acceptor_loss	1.0000	5

AlphaMissense

2,317 missense substitutions predicted likely pathogenic (of 4,190 scored), across 508 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M420	9	0.971	0.998
M316	9	0.863	0.990
D306	8	0.999	1.000
F327	8	0.999	1.000
D330	8	0.999	1.000
D442	8	0.999	1.000
N394	8	0.998	1.000
N443	8	0.997	1.000
D419	8	0.996	0.999
F555	8	0.995	1.000
F580	8	0.993	1.000
F440	8	0.990	0.999
H523	8	0.990	0.999
N627	8	0.990	1.000
N239	8	0.987	0.999
D70	8	0.985	0.997
F236	8	0.980	1.000
D317	8	0.980	0.995
F521	8	0.977	0.999
F40	8	0.975	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.93e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.21e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.00056
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000728

Disease associations

OMIM: gene MIM:604045 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST009723_51	Vertical cup-disc ratio (adjusted for vertical disc diameter)	1e-13
GCST006135_9	Cortical amyloid beta load	4e-7
GCST006135_10	Cortical amyloid beta load	4e-6
GCST006135_8	Cortical amyloid beta load	5e-6
GCST006135_13	Cortical amyloid beta load	6e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0006939	cup-to-disc ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1795116 (SINGLE PROTEIN), CHEMBL3137261 (PROTEIN COMPLEX), CHEMBL4748215 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483002 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PRMT5 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
PEMRAMETOSTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,433 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1088977	ADEMETIONINE	3	1,588
CHEMBL4466233	PEMRAMETOSTAT	2	567
CHEMBL1214186	SINEFUNGIN	2	2,181
CHEMBL142304	STILBAMIDINE	2	891
CHEMBL4249337	ONAMETOSTAT	1	206

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein arginine N-methyltransferases

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
onametostat	Inhibition	9.2	pKd
ralometostat	Binding	8.72	pKd
EPZ015666	Inhibition	8.3	pKi
AZ-PRMT5i-1	Inhibition	8.26	pIC50
GSK591	Inhibition	7.96	pIC50
navlimetostat	Inhibition	7.92	pIC50
LLY-283	Inhibition	7.7	pIC50
PRMT5 inhibitor D3	Inhibition	7.68	pIC50
pemrametostat	Inhibition	7.33	pIC50
DS-437	Inhibition	5.23	pIC50

Binding affinities (BindingDB)

3615 measured of 4942 human assays (4954 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5180177	KI	0.02 nM
CHEMBL5426836	KI	0.05 nM
CHEMBL4872234	KI	0.05 nM
CHEMBL6163998	KI	0.1 nM
CHEMBL6166947	KI	0.1 nM
CHEMBL6143724	KI	0.1 nM
CHEMBL6143495	KI	0.1 nM
CHEMBL6148651	KI	0.1 nM
CHEMBL5203719	IC50	0.13 nM
CHEMBL4564327	IC50	0.16 nM
CHEMBL6145605	KI	0.2 nM
CHEMBL6168533	KI	0.2 nM
(2S,3S,4R,5R)-2-[(1R)-1-(3,4-dichlorocyclohexa-2,4-dien-1-yl)-1-hydroxyethyl]-5-[(4E)-4-hydroxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-(2-amino-3-chloroquinolin-7-yl)ethyl]-5-[(4Z)-4-methoxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(4R)-6-bromo-4-ethyl-2-[(2S)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-3,4-dihydroisoquinolin-1-one	IC50	0.21 nM	US-11098059
(4R)-4-ethyl-2-[(2S)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-3,4-dihydroisoquinolin-1-one	IC50	0.24 nM	US-11098059
CHEMBL4541714	IC50	0.25 nM
6-(2-cyclopropyl-1,2,4-triazol-3-yl)-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]spiro[3H-isoquinoline-4,1’-cyclobutane]-1-one	IC50	0.29 nM	US-11098059
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(2-methylhydrazinyl)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.3 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(4S)-6-bromo-4-ethyl-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-3,4-dihydroisoquinolin-1-one	IC50	0.31 nM	US-11098059
CHEMBL4577464	IC50	0.32 nM
(1S,2R,3S,5R)-3-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]-5-[(4Z)-4-hydroxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.33 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
6-(5,8-dioxa-2-azatricyclo[4.3.0.03,7]nonane-2-carbonyl)-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.35 nM	US-11098059
(4R)-4-ethyl-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-3,4-dihydroisoquinolin-1-one	IC50	0.36 nM	US-11098059
CHEMBL2169919	IC50	0.4 nM
CHEMBL4454890	IC50	0.4 nM
CHEMBL5187591	IC50	0.4 nM
CHEMBL6133844	KI	0.4 nM
6-(2-cyclopropyl-1,2,4-triazol-3-yl)-4-ethyl-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-3,4-dihydroisoquinolin-1-one	IC50	0.4 nM	US-11098059
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
CHEMBL6176251	IC50	0.42 nM
2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.44 nM	US-11098059
6-(2-cyclopropyl-1,2,4-triazol-3-yl)-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.47 nM	US-11098059
(2R,3S,4R,5R)-2-[(2-amino-3-bromoquinolin-7-yl)oxymethyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3-methyloxolane-3,4-diol	IC50	0.5 nM	US-10570140: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.5 nM	US-11098059
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]benzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-5-chlorobenzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-4-chlorobenzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-4-methoxybenzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-5-methylbenzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
2-[4-[4-(aminomethyl)-1-oxo-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-6-methoxybenzonitrile	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
4-(aminomethyl)-6-[5-(2-methoxyphenoxy)-3-pyridinyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	0.5 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
6-[(1R,5S)-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.52 nM	US-11098059
2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-6-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-3H-isoquinolin-1-one	IC50	0.53 nM	US-11098059
CHEMBL4536042	IC50	0.6 nM
CHEMBL6167929	KI	0.6 nM
US11220524, Example 20	IC50	0.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-difluorophenyl)-hydroxymethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
4-(aminomethyl)-6-[5-(2,4-dimethylphenoxy)-3-pyridinyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	0.6 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
4-(aminomethyl)-6-[3-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	0.6 nM	US-11479551: MTA-cooperative PRMT5 inhibitors

ChEMBL bioactivities

4903 potent at pChembl≥5 of 5224 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.94	Kd	0.0114	nM	CHEMBL4563402
10.70	Ki	0.02	nM	CHEMBL4441584
10.70	Ki	0.02	nM	CHEMBL5180177
10.30	Ki	0.05	nM	CHEMBL5426836
10.30	Ki	0.05	nM	CHEMBL4872234
10.00	Ki	0.1	nM	CHEMBL6163998
10.00	Ki	0.1	nM	CHEMBL6166947
10.00	Ki	0.1	nM	CHEMBL6143724
10.00	Ki	0.1	nM	CHEMBL6143495
10.00	Ki	0.1	nM	CHEMBL6148651
9.89	IC50	0.13	nM	ONAMETOSTAT
9.89	IC50	0.13	nM	CHEMBL5203719
9.85	IC50	0.14	nM	ONAMETOSTAT
9.80	IC50	0.16	nM	CHEMBL4564327
9.80	IC50	0.16	nM	CHEMBL4541714
9.70	IC50	0.2	nM	CHEMBL5865819
9.70	IC50	0.2	nM	CHEMBL5796835
9.70	Ki	0.2	nM	CHEMBL6145605
9.70	Ki	0.2	nM	CHEMBL6168533
9.68	IC50	0.21	nM	CHEMBL5757382
9.62	Kd	0.241	nM	CHEMBL4441584
9.62	IC50	0.24	nM	CHEMBL5790903
9.60	IC50	0.25	nM	CHEMBL4541714
9.60	IC50	0.25	nM	ONAMETOSTAT
9.54	IC50	0.29	nM	CHEMBL5747648
9.52	IC50	0.3	nM	CHEMBL5861732
9.51	IC50	0.31	nM	CHEMBL5810961
9.49	IC50	0.32	nM	CHEMBL4577464
9.48	IC50	0.33	nM	CHEMBL5894143
9.46	IC50	0.35	nM	CHEMBL5863900
9.44	IC50	0.36	nM	CHEMBL5774632
9.40	IC50	0.4	nM	CHEMBL4454890
9.40	IC50	0.4	nM	CHEMBL4543007
9.40	IC50	0.4	nM	CHEMBL5187591
9.40	IC50	0.4	nM	CHEMBL5973136
9.40	IC50	0.4	nM	CHEMBL5761913
9.40	IC50	0.4	nM	CHEMBL6103457
9.40	Ki	0.4	nM	CHEMBL6133844
9.38	IC50	0.42	nM	CHEMBL5283866
9.38	IC50	0.42	nM	CHEMBL5559161
9.38	IC50	0.42	nM	CHEMBL5560909
9.38	IC50	0.42	nM	CHEMBL5613744
9.38	IC50	0.42	nM	CHEMBL6176251
9.36	IC50	0.44	nM	CHEMBL5755426
9.33	IC50	0.47	nM	CHEMBL6055014
9.30	IC50	0.5	nM	CHEMBL6007359
9.30	IC50	0.5	nM	CHEMBL5945691
9.30	IC50	0.5	nM	CHEMBL5076664
9.30	IC50	0.5	nM	CHEMBL5789744
9.30	IC50	0.5	nM	CHEMBL5965955

PubChem BioAssay actives

1011 with measured affinity, of 1975 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
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(4-chloro-3-fluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1593837: Inhibition of PRMT5 (unknown origin)	ki	<0.0001	uM
(1S,2S,3S,5R)-3-[[6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl]oxy]-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1997206: Binding affinity to N-terminal 6xHis-tagged full length human PRMT5/MEP50 expressed in sf21 cells using S-Adenosyl-L-methionine as substrate assessed as dissociation constant incubated for 25 to 60 mins by liquid scintillation analysis	kd	<0.0001	uM
2-[4-[4-(aminomethyl)-1-oxo-2H-phthalazin-6-yl]-1-methylpyrazol-5-yl]-4-chloro-6-cyclopropyloxy-3-fluorobenzonitrile	1825252: Binding affinity to human PRMT5 assessed as dissociation constant in presence of MTA by SPR analysis	kd	<0.0001	uM
N-(6-amino-5-ethyl-3-pyridinyl)-2-[(2R,5S)-5-methyl-2-[2-(1-methylpiperidin-4-yl)-1,3-benzothiazol-5-yl]piperidin-1-yl]-2-oxoacetamide	2234954: Inhibition of PRMT5/MEP50 (unknown origin) in absence of MTA	ki	<0.0001	uM
(2S,3S,4R,5S)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(4-chloro-3-fluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1882380: Binding affinity to PRMT5 (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
(1S,2R,3S,5R)-3-[2-(2-amino-3-bromoquinolin-7-yl)ethyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1530643: Inhibition of full-length human N-terminal FLAG-tagged PRMT5 expressed in Sf9 insect cells using histone H2A as peptide after 120 mins in presence of SAM by high throughput mass spectrometer assay	ic50	0.0001	uM
2-amino-3-methyl-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
7-amino-6-methyl-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,8-naphthyridine-3-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
2-amino-3-methyl-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,7-naphthyridine-6-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
2-amino-3-methyl-N-[(7R)-4,5,6,7-tetrahydro-1H-indazol-7-yl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	2253822: Binding affinity to PRMT5 (unknown origin) assessed as inhibition constant	ki	0.0001	uM
4-amino-N-methyl-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c]quinoline-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
4-amino-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c][1,7]naphthyridine-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
4-amino-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c]quinoline-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
4-amino-N-ethyl-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c]quinoline-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
[(3R)-4-amino-3-methyl-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl]-[(3S)-3-[4-(trifluoromethyl)phenyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)-[(3S)-3-[4-(trifluoromethyl)phenyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)-[(2R)-2-[4-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c]quinolin-8-yl)-[(3S)-3-[5-(trifluoromethyl)-2-pyridinyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)-[(3R,5S)-3-methyl-5-[4-(trifluoromethyl)phenyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c]quinolin-8-yl)-[(3S)-3-(4-chlorophenyl)morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c]quinolin-8-yl)-[(3S)-3-[4-(trifluoromethyl)phenyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
4-amino-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c][1,8]naphthyridine-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
4-amino-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,3-dihydro-1H-cyclopenta[c]quinoline-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(1R,2S,3R,5S)-3-[2-(2-amino-3-bromoquinolin-7-yl)ethyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1882374: Inhibition of PRMT5 (unknown origin)	ic50	0.0001	uM
4-amino-7-fluoro-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-1,3-dihydrofuro[3,4-c]quinoline-8-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
2-amino-3-methyl-N-[(4R)-4,5,6,7-tetrahydro-1H-indazol-4-yl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	1997247: Binding affinity to PRMT5/MEP50 (unknown origin) using histone H4 peptide assessed as inhibition constant preincubated for 24 hrs followed by substrate addition and measured for 2 hrs in the presence of SAM by MTase-Glo Methyl Transferase Assay	ki	0.0001	uM
(4-amino-1,3-dihydrofuro[3,4-c]quinolin-8-yl)-[3-[5-(trifluoromethyl)-2-pyridinyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0001	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(2-aminoquinolin-7-yl)ethyl]cyclopentane-1,2-diol	1593845: Inhibition of PRMT5 in human A549 cells assessed as reduction in sDMA production after 48 hrs by Hoechst Stain/HCS CellMask Deep Red Stain based immunohistochemistry method	ic50	0.0002	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-chloro-3-methylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0002	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(2,3-dimethylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0002	uM
2-amino-3-chloro-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0002	uM
(4-amino-1,3-dihydrofuro[3,4-c]quinolin-8-yl)-[(3S)-3-[6-(trifluoromethyl)-3-pyridinyl]morpholin-4-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0002	uM
methyl 2-[[2-[(6-methoxy-1H-benzimidazol-2-yl)sulfanyl]acetyl]amino]benzoate	1882374: Inhibition of PRMT5 (unknown origin)	ic50	0.0003	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-fluoro-3-methylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0003	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]cyclopentane-1,2-diol	1593845: Inhibition of PRMT5 in human A549 cells assessed as reduction in sDMA production after 48 hrs by Hoechst Stain/HCS CellMask Deep Red Stain based immunohistochemistry method	ic50	0.0004	uM
(1S,2R,3S,5R)-3-[4-(6-amino-2-pyridinyl)butyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0004	uM
(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)-[(2R)-4,4-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0004	uM
(1R,2S,3R,5S)-3-[3-(6-amino-2-pyridinyl)propyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1882374: Inhibition of PRMT5 (unknown origin)	ic50	0.0004	uM
(2S)-2-amino-N-[2-[[(2R)-1-amino-4-[[amino-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethylamino]methylidene]amino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(diaminomethylideneamino)pentanamide	1946282: Inhibition of human PRMT5 by fluorescence-based SAHH-coupled assay	ic50	0.0004	uM
(2S)-5-amino-N-[(2R)-1-amino-5-[[N’-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]carbamimidoyl]amino]-1-oxopentan-2-yl]-2-[[2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]pentanamide	2073632: Inhibition of PRMT5 (unknown origin) by HotSpot profiling analysis	ic50	0.0004	uM
(2S)-2-amino-N-[2-[[(2S)-1-amino-4-[[N’-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]carbamimidoyl]amino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(diaminomethylideneamino)pentanamide	2074356: Inhibition of PRMT5 (unknown origin)	ic50	0.0004	uM
(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]pentanoyl]amino]-5-[[N’-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]carbamimidoyl]amino]pentanoic acid	2127549: Inhibition of human PRMT5/MEP50 using Histone H2 as substrate and SAM as cofactor by radiometric HotSpot assay	ic50	0.0004	uM
(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-[[N’-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]carbamimidoyl]amino]pentanamide	2222248: Inhibition of PRMT5 (unknown origin)	ic50	0.0004	uM
(2S)-2-amino-5-[[3-[[(2S,3S,4R,5S)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propylamino]methylamino]pentanamide	2265459: Inhibition of PRMT5 (unknown origin)	ic50	0.0004	uM
(2R,3R,3aS,6S,6aR)-6-[(2-amino-3-bromoquinolin-7-yl)methyl]-2-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3,3a-diol	1749891: Inhibition of PRMT5 (unknown origin) assessed as inhibition of symmetric dimethylation of arginine incubated for 3 days by fluorescence based cellular target engagement assay	ec50	0.0005	uM
2-amino-3-methyl-N-(2-methylpropyl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0005	uM
(2R,3S,4R,5R)-2-[(R)-(4-chlorophenyl)-hydroxymethyl]-5-(4-hydrazinylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol	1593838: Inhibition of PRMT5 (unknown origin)/MEP50 (unknown origin) using histone H2 as substrate preincubated for 15 to 20 mins followed by S-[methyl-3H]adenosyl-L-methionine addition measured after 60 mins by liquid scintillation counting	ic50	0.0006	uM
2-amino-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	2239706: Inhibition of PRMT5/MEP50 (unknown origin) preincubated with compound for 24 hrs in presence of SAM and MTA followed by Histone H4 (1-21)-Lys(Biotin) peptide addition and measured after 2 hrs by MTase-Glo reagent based assay	ki	0.0006	uM
(1S,2R,3aR,4S,6aR)-2-(4-amino-5-fluoropyrrolo[2,3-d]pyrimidin-7-yl)-4-[(2-amino-3-fluoroquinolin-7-yl)methyl]-2,3,3a,4,5,6-hexahydro-1H-pentalene-1,6a-diol	1749891: Inhibition of PRMT5 (unknown origin) assessed as inhibition of symmetric dimethylation of arginine incubated for 3 days by fluorescence based cellular target engagement assay	ec50	0.0007	uM
N-(4-amino-1,3-dihydrofuro[3,4-c]pyridin-7-yl)-2-[(2R,5S)-5-methyl-2-[2-(1-methylpiperidin-4-yl)-1,3-benzothiazol-5-yl]piperidin-1-yl]-2-oxoacetamide	2234912: Inhibition of PRMT5 in MTAP-null human HAP1 cells assessed as decrease in SDMA level incubated for 24 hrs by ICW assay	ic50	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
GSK3235025	decreases activity, decreases expression	5
bisphenol A	affects expression, decreases expression	3
Ribavirin	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
OTX015	affects binding, decreases reaction, decreases expression	1
bisphenol F	increases expression	1
JNJ-64619178	decreases activity	1
lly-283	decreases activity	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
PP242	increases activity	1

ChEMBL screening assays

655 unique, capped per target: 624 binding, 30 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1804753	Binding	Inhibition of PRMT5-mediated methylation of histone H4 at 100 uM after 90 mins by scintillation counting in presence of S-adenosyl-l-[methyl-3H]methionine	Novel 3,5-bis(bromohydroxybenzylidene)piperidin-4-ones as coactivator-associated arginine methyltransferase 1 inhibitors: enzyme selectivity and cellular activity. — *J Med Chem*
CHEMBL5210098	Functional	Affinity Phenotypic Cellular interaction (MTT assay (cell proliferation in Z-138 cells)) EUB0000198b PRMT5	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3
CHEMBL5547649	Toxicity	Inhibition of PRMT5 in human HAP1 cells harboring wild type MTAP incubated for 24 hrs by SDMA in-cell western assay	Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP-Deleted Cancers. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRMT5 across ~30M SureChEMBL compounds — explore on Sugi Predict.