PRMT9

Summary

PRMT9 (protein arginine methyltransferase 9, HGNC:25099) is a protein-coding gene on chromosome 4q31.23, encoding Protein arginine N-methyltransferase 9 (Q6P2P2). Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).

This gene encodes a type II methyltransferase. Post-translational modification of target proteins by PRMTs plays an important regulatory role in many biological processes, whereby PRMTs methylate arginine residues by transferring methyl groups from S-adenosyl-L-methionine to the guanidino nitrogen atoms of arginine. The protein encoded by this gene methylates spliceosome associated protein 145 to regulate alternative splicing and acts as a modulator of small nuclear ribonucleoprotein maturation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 90826 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 138 total — 19 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_138364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25099
Approved symbol	PRMT9
Name	protein arginine methyltransferase 9
Location	4q31.23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46629
Ensembl gene	ENSG00000164169
Ensembl biotype	protein_coding
OMIM	616125
Entrez	90826

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000322396, ENST00000510269, ENST00000511687, ENST00000514886, ENST00000865624, ENST00000865625, ENST00000865626, ENST00000940714, ENST00000940715, ENST00000960614, ENST00000960615

RefSeq mRNA: 6 — MANE Select: NM_138364 NM_001304458, NM_001350141, NM_001350142, NM_001350143, NM_001350144, NM_138364

CCDS: CCDS3771

Canonical transcript exons

ENST00000322396 — 12 exons

Exon	Start	End
ENSE00001224431	147637785	147638747
ENSE00001334399	147680323	147680471
ENSE00002047919	147683799	147684163
ENSE00003475849	147672959	147673126
ENSE00003482499	147668539	147668645
ENSE00003493598	147657792	147657975
ENSE00003513278	147642787	147642940
ENSE00003523970	147673638	147673874
ENSE00003571684	147670641	147670743
ENSE00003607173	147653852	147654566
ENSE00003622066	147660846	147661038
ENSE00003663555	147638960	147639082

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 92.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3928 / max 320.8438, expressed in 1722 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54275	5.6841	1688
54274	1.6717	600
54273	0.0370	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.41	gold quality
left ovary	UBERON:0002119	87.45	gold quality
right ovary	UBERON:0002118	87.33	gold quality
right testis	UBERON:0004534	86.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.32	gold quality
lower esophagus mucosa	UBERON:0035834	86.09	gold quality
oocyte	CL:0000023	85.71	gold quality
tibialis anterior	UBERON:0001385	85.71	silver quality
left testis	UBERON:0004533	85.70	gold quality
adenohypophysis	UBERON:0002196	85.63	gold quality
left lobe of thyroid gland	UBERON:0001120	85.58	gold quality
right lobe of thyroid gland	UBERON:0001119	85.57	gold quality
thyroid gland	UBERON:0002046	85.26	gold quality
testis	UBERON:0000473	85.15	gold quality
ovary	UBERON:0000992	84.63	gold quality
adrenal tissue	UBERON:0018303	84.29	gold quality
mucosa of stomach	UBERON:0001199	83.34	gold quality
pituitary gland	UBERON:0000007	83.14	gold quality
left uterine tube	UBERON:0001303	82.91	gold quality
left adrenal gland cortex	UBERON:0035825	82.77	gold quality
pigmented layer of retina	UBERON:0001782	82.46	gold quality
tibial artery	UBERON:0007610	82.45	gold quality
popliteal artery	UBERON:0002250	82.44	gold quality
adrenal cortex	UBERON:0001235	82.06	gold quality
adrenal gland	UBERON:0002369	82.01	gold quality
right adrenal gland cortex	UBERON:0035827	81.95	gold quality
right adrenal gland	UBERON:0001233	81.90	gold quality
left adrenal gland	UBERON:0001234	81.74	gold quality
sperm	CL:0000019	81.65	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	545.52
E-CURD-46	yes	25.00
E-MTAB-6701	yes	15.55
E-CURD-122	yes	9.80
E-ANND-3	yes	9.78
E-HCAD-10	yes	7.64
E-MTAB-6678	yes	5.82
E-CURD-112	no	2.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting PRMT9, 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-4668-3P	100.00	68.74	2635
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3180-5P	99.82	69.12	2422
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-498-5P	99.76	69.64	1807
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4643	99.49	67.63	1791

Literature-anchored findings (GeneRIF, showing 8)

• PRMT9 is a type II methyltransferase that methylates the splicing factor SAP145. (PMID:25737013)
• The decrease in PRMT10 was canceled by knockdown of AR or an AR antagonist. These results indicate that PRMT10 plays an important role in androgen-dependent proliferation of prostate cancer cells (PMID:25799006)
• Although amino acid substitutions of residues surrounding Arg-508 had no great effect on PRMT9 recognition of SF3B2, moving the arginine residue within this sequence abolished methylation. (PMID:25979344)
• Mechanistically, miR-543 inhibited PRMT9-enhanced cell oxidative phosphorylation, while miR-543 depletion promoted PRMT9-increased HIF-1alpha instability and inhibited glycolysis in osteosarcoma (OS) cells. Clinically, miR-543 expression was negatively correlated with PRMT9 expression in OS tissues. (PMID:27911265)
• Study demonstrated that PRMT9 is an oncogene that plays an important role in hepatocellular carcinoma cells invasion and metastasis through EMT by regulating Snail expression via activation of the PI3K/Akt/GSK-3beta/Snail signaling pathway. (PMID:29603830)
• The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation. (PMID:36028484)
• Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression. (PMID:37715221)
• Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing. (PMID:38561334)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prmt9	ENSDARG00000036755
mus_musculus	Prmt9	ENSMUSG00000037134
rattus_norvegicus	Prmt9	ENSRNOG00000012928
drosophila_melanogaster	Art2	FBGN0031592
caenorhabditis_elegans		WBGENE00011939

Paralogs (7): PRMT8 (ENSG00000111218), PRMT1 (ENSG00000126457), PRMT7 (ENSG00000132600), CARM1 (ENSG00000142453), PRMT2 (ENSG00000160310), PRMT3 (ENSG00000185238), PRMT6 (ENSG00000198890)

Protein

Protein identifiers

Protein arginine N-methyltransferase 9 — Q6P2P2 (reviewed: Q6P2P2)

Alternative names: Protein arginine N-methyltransferase 10

All UniProt accessions (2): D6REN0, Q6P2P2

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). Specifically mediates the symmetrical dimethylation of SF3B2. Involved in the regulation of alternative splicing of pre-mRNA.

Subunit / interactions. Found in a complex with PRMT9, SF3B2 and SF3B4. Interacts with SF3B2.

Subcellular location. Cytoplasm.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P2P2-1	1	yes
Q6P2P2-2	2

RefSeq proteins (6): NP_001291387, NP_001337070, NP_001337071, NP_001337072, NP_001337073, NP_612373* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR025799	Arg_MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR055135	PRMT_dom	Domain

Pfam: PF06325, PF22528

Enzyme classification (BRENDA):

• EC 2.1.1.320 — 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), 1 shown:

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

UniProt features (79 total): strand 37, helix 24, mutagenesis site 4, repeat 3, turn 3, sequence conflict 2, domain 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7RBQ	X-RAY DIFFRACTION	2.2
9AY9	X-RAY DIFFRACTION	2.22
6PDM	X-RAY DIFFRACTION	2.45
7T39	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P2P2-F1	86.94	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
258	abolishes enzymatic activity.
260	abolishes enzymatic activity.
431	8-fold increase in mma production and almost complete elimination of sdma production.
182–185	loss of interaction with sf3b2; abolishes enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION, EVI1_04, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_N_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOMF_HISTONE_METHYLTRANSFERASE_ACTIVITY, GOBP_MRNA_PROCESSING, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, GCNP_SHH_UP_EARLY.V1_UP, GOMF_PROTEIN_ARGININE_N_METHYLTRANSFERASE_ACTIVITY, EIF4E_DN

GO Biological Process (5): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), mRNA processing (GO:0006397), methylation (GO:0032259), peptidyl-arginine methylation (GO:0018216)

GO Molecular Function (7): protein-arginine N-methyltransferase activity (GO:0016274), protein-arginine omega-N symmetric methyltransferase activity (GO:0035243), histone methyltransferase activity (GO:0042054), protein binding (GO:0005515), methyltransferase activity (GO:0008168), protein methyltransferase activity (GO:0008276), transferase activity (GO:0016740)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein methyltransferase activity	2
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA processing	1
mRNA metabolic process	1
metabolic process	1
protein methylation	1
peptidyl-arginine modification	1
arginine N-methyltransferase activity	1
protein-arginine N-methyltransferase activity	1
histone modifying activity	1
binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRMT9	PRMT5	O14744	735
PRMT9	TMEM184C	Q9NVA4	716
PRMT9	FBXO10	Q9UK96	666
PRMT9	SF3B2	Q13435	530
PRMT9	SF3B4	Q15427	472
PRMT9	RPS2	P15880	407
PRMT9	PRMT7	Q9NVM4	402
PRMT9	FBXO11	Q86XK2	387
PRMT9	JMJD7	P0C870	352
PRMT9	TTC21B	Q7Z4L5	344
PRMT9	ACBD6	Q9BR61	344
PRMT9	PRMT3	O60678	340
PRMT9	SNRPD3	P43331	329
PRMT9	ELP2	Q6IA86	327
PRMT9	MBD3L5	A6NJ08	317

IntAct

50 interactions, top by confidence:

A	B	Type	Score
SF3B2	SF3B4	psi-mi:“MI:0914”(association)	0.910
PRMT9	SF3B2	psi-mi:“MI:0914”(association)	0.750
PRMT9	SF3B2	psi-mi:“MI:0915”(physical association)	0.750
PRMT9	SF3B2	psi-mi:“MI:0213”(methylation reaction)	0.750
PRMT9	SF3B4	psi-mi:“MI:0915”(physical association)	0.660
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
SF3B4	SF3B1	psi-mi:“MI:0914”(association)	0.610
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
ZBTB42	MID1	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
ZBTB42	GGPS1	psi-mi:“MI:0914”(association)	0.530
TACC3	DHRS2	psi-mi:“MI:0914”(association)	0.350
Dync1li1	SSR3	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RAB5A	ENTPD6	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
PNKD	EXOC5	psi-mi:“MI:0914”(association)	0.350
ST6GAL1	HLA-C	psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3F	psi-mi:“MI:0914”(association)	0.350
RAF1	PRPF3	psi-mi:“MI:0914”(association)	0.350
RAF1	ARID1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), PRMT9 (Proximity Label-MS)

ESM2 similar proteins: A0JMU5, A1A4L5, A2AV36, A2Y8B9, B0X4N1, B3DLB3, B3M1E1, B3MF31, B3P4N5, B4GZ20, B4HJC0, B4I8G2, B4JXV2, B4KA23, B4LVS8, B4NKI9, B4P925, B4PVH6, B4QI55, B4QVW6, B6DMK2, D9IVE5, O14727, O60678, O70467, O88879, Q0V9P1, Q16NS8, Q29B63, Q3EBC8, Q3U213, Q3U3W5, Q4SBY6, Q5RAY7, Q5ZIB9, Q6P2P2, Q6P5U7, Q6PCI6, Q7QIL2, Q80VJ4

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
mRNA Splicing - Major Pathway	5	7.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	0
Uncertain significance	112
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1704224	NM_138364.4(PRMT9):c.106_107del (p.Leu36fs)	Pathogenic
1704225	NM_138364.4(PRMT9):c.565G>A (p.Gly189Arg)	Pathogenic
1704226	NM_138364.4(PRMT9):c.576-2A>G	Pathogenic
1704227	NM_138364.4(PRMT9):c.836del (p.Leu279fs)	Pathogenic
1704228	NM_138364.3:c.(846+1_847-1)_(1330+1_1331-1)del	Pathogenic
1704229	NM_138364.4(PRMT9):c.1075C>T (p.Arg359Ter)	Pathogenic
1704230	NM_138364.4(PRMT9):c.1143del (p.Gln382fs)	Pathogenic
1704232	NM_138364.4(PRMT9):c.1318C>T (p.Gln440Ter)	Pathogenic
1704234	NM_138364.4(PRMT9):c.219G>A (p.Trp73Ter)	Pathogenic
1704236	NM_138364.4(PRMT9):c.1918dup (p.Val640fs)	Pathogenic
1704237	NM_138364.4(PRMT9):c.2342del (p.Gly781fs)	Pathogenic
1704238	NM_138364.4(PRMT9):c.2356dup (p.Ile786fs)	Pathogenic
1704240	NM_138364.4(PRMT9):c.257T>A (p.Leu86Ter)	Pathogenic
1704241	NM_138364.4(PRMT9):c.258_261del (p.Leu87fs)	Pathogenic
1704242	NM_138364.4(PRMT9):c.270T>G (p.Tyr90Ter)	Pathogenic
1704243	NM_138364.4(PRMT9):c.415G>T (p.Glu139Ter)	Pathogenic
1704244	NM_138364.4(PRMT9):c.491del (p.Thr164fs)	Pathogenic
1704245	NM_138364.4(PRMT9):c.545del (p.Leu182fs)	Pathogenic
4530584	NM_138364.4(PRMT9):c.734_735del (p.Ile245fs)	Pathogenic

SpliceAI

1927 predictions. Top by Δscore:

Variant	Effect	Δscore
4:147638747:CC:C	acceptor_loss	1.0000
4:147639081:ACCTA:A	acceptor_loss	1.0000
4:147639082:CCTA:C	acceptor_loss	1.0000
4:147639083:CTA:C	acceptor_loss	1.0000
4:147639084:T:A	acceptor_loss	1.0000
4:147642938:CAC:C	acceptor_gain	1.0000
4:147654579:G:GC	acceptor_gain	1.0000
4:147657787:CCTA:C	donor_loss	1.0000
4:147657788:CTAC:C	donor_loss	1.0000
4:147657789:TACCT:T	donor_loss	1.0000
4:147657790:ACCTG:A	donor_loss	1.0000
4:147660830:A:C	donor_gain	1.0000
4:147660840:TTTCA:T	donor_loss	1.0000
4:147660841:TTCA:T	donor_loss	1.0000
4:147660842:TCACC:T	donor_loss	1.0000
4:147660843:CAC:C	donor_loss	1.0000
4:147660845:CC:C	donor_loss	1.0000
4:147661037:CT:C	acceptor_gain	1.0000
4:147661039:C:CC	acceptor_gain	1.0000
4:147668646:C:CC	acceptor_gain	1.0000
4:147672999:T:TA	donor_gain	1.0000
4:147673025:T:TA	donor_gain	1.0000
4:147673122:ACATG:A	acceptor_gain	1.0000
4:147673123:CATG:C	acceptor_gain	1.0000
4:147673123:CATGC:C	acceptor_gain	1.0000
4:147673124:ATG:A	acceptor_gain	1.0000
4:147673125:TG:T	acceptor_gain	1.0000
4:147673127:C:CC	acceptor_gain	1.0000
4:147680319:AAACC:A	donor_loss	1.0000
4:147680320:AACCT:A	donor_loss	1.0000

AlphaMissense

5608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:147673759:A:G	W152R	1.000
4:147673759:A:T	W152R	1.000
4:147653931:A:G	W656R	0.999
4:147653931:A:T	W656R	0.999
4:147680339:C:A	G108W	0.999
4:147657828:A:G	W432R	0.998
4:147657828:A:T	W432R	0.998
4:147670732:A:T	V252D	0.998
4:147673757:C:A	W152C	0.998
4:147673757:C:G	W152C	0.998
4:147673855:C:G	A120P	0.998
4:147680329:A:G	L111P	0.998
4:147680338:C:T	G108E	0.998
4:147680339:C:G	G108R	0.998
4:147680339:C:T	G108R	0.998
4:147657826:C:A	W432C	0.997
4:147657826:C:G	W432C	0.997
4:147670723:T:A	E255V	0.997
4:147673126:G:C	S192R	0.997
4:147673126:G:T	S192R	0.997
4:147673639:T:G	S192R	0.997
4:147673727:C:A	R162S	0.997
4:147673727:C:G	R162S	0.997
4:147654073:A:C	S608R	0.996
4:147654073:A:T	S608R	0.996
4:147654075:T:G	S608R	0.996
4:147673834:C:G	A127P	0.996
4:147683857:G:T	A44D	0.996
4:147642932:A:G	L685P	0.995
4:147670735:A:G	L251P	0.995

dbSNP variants (sampled 300 via entrez): RS1000014915 (4:147659219 G>A), RS1000066645 (4:147676092 C>A,T), RS1000178961 (4:147665971 C>T), RS1000211217 (4:147644115 A>T), RS1000351255 (4:147676937 C>A,T), RS1000364517 (4:147664905 G>A), RS1000380371 (4:147672612 T>G), RS1000469818 (4:147658989 C>G,T), RS1000483172 (4:147679116 C>A,T), RS1000553842 (4:147639139 G>A), RS1000606159 (4:147638875 T>C,G), RS1000661205 (4:147684604 A>T), RS1000668543 (4:147685493 C>A,T), RS10007255 (4:147664890 A>C,G), RS1000730763 (4:147673040 G>C)

Disease associations

OMIM: gene MIM:616125 | disease phenotypes: MIM:614209

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal recessive
intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	Limited	Autosomal recessive
Mendelian neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (4): Meckel syndrome, type 9 (MONDO:0013630), intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (MONDO:0060760), Mendelian neurodevelopmental disorder (MONDO:0100500), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): Meckel syndrome (Orphanet:564)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_612	Obesity-related traits	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004697	estradiol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105724 (SINGLE PROTEIN)

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

ChEMBL bioactivities

12 potent at pChembl≥5 of 13 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	CHEMBL5558016
6.84	IC50	145	nM	CHEMBL5558016
6.73	Kd	188	nM	CHEMBL5396270
6.70	IC50	200	nM	CHEMBL5396270
6.05	IC50	890	nM	CHEMBL5199380
5.99	IC50	1020	nM	CHEMBL5406557
5.92	IC50	1200	nM	CHEMBL5202088
5.89	IC50	1300	nM	CHEMBL5186617
5.88	IC50	1320	nM	CHEMBL5170047
5.61	IC50	2470	nM	CHEMBL5408585
5.24	IC50	5800	nM	CHEMBL5206272
5.03	IC50	9300	nM	CHEMBL5173678

PubChem BioAssay actives

12 with measured affinity, of 58 total; 10 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,5S)-2-(4-amino-5-methylpyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[(2-tert-butyl-3-pyridinyl)methylamino]ethylsulfanylmethyl]oxolane-3,4-diol	2074376: Inhibition of PRMT9 (unknown origin)	ic50	0.0100	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	2012363: Binding affinity to N-terminal/C-terminal FLAG/6His-tagged human PRMT9 (2 to 845 residues) assessed as dissociation constant by SPR assay	kd	0.1880	uM
methyl 6-[3-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]propylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	0.8900	uM
methyl 6-[6-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]hexylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	1.0200	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	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	1.2000	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	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	1.3000	uM
methyl 6-[4-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]butylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	1.3200	uM
methyl 6-[2-[[N’-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamimidoyl]amino]ethylcarbamoylamino]-4-hydroxynaphthalene-2-carboxylate	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	2.4700	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	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	5.8000	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	2012344: Inhibition of human recombinant PRMT9 using biotinylated SF3B2(500 to 519 residues) as substrate and SAM as cosubstrate pre-incubated with compound for 30 mins followed by substrate addition measured after 60 mins by AlphaLISA assay	ic50	9.3000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
jinfukang	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Cadmium	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases reaction, increases expression	1

ChEMBL screening assays

40 unique, capped per target: 40 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4005630	Binding	Inhibition of PRMT9 (unknown origin) at 10 uM using biotin-labeled peptide as substrate and [3H]-SAM measured after 1 hr by scintillation proximity assay	Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2HZ	HAP1 PRMT9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder