Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6OBK3K)

• DOT Name: Protein arginine N-methyltransferase 9 (PRMT9)
• Synonyms: Protein arginine N-methyltransferase 10; EC 2.1.1.320
• Gene Name: PRMT9
• Related Disease:
  Bone osteosarcoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities
  Osteosarcoma
• UniProt ID: ANM9_HUMAN
• PDB ID: 6PDM; 7RBQ; 7T39
• EC Number: 2.1.1.320
• Pfam ID: PF06325
• Sequence:
  MSNSRPRSRRDAGGGAGAAGRDELVSRSLQSAEHCLGVQDFGTAYAHYLLVLSLAPELKH
  DVKETFQYTLFRWAEELDALSRIQDLLGCYEQALELFPDDEVICNSMGEHLFRMGFRDEA
  AGYFHKAVKLNPDFSDAKENFYRVANWLVERWHFIMLNDTKRNTIYNAAIQKAVCLGSKS
  VLDIGAGTGILSMFAKKAGAHSVYACELSKTMYELACDVVAANKMEAGIKLLHTKSLDIE
  IPKHIPERVSLVVTETVDAGLFGEGIVESLIHAWEHLLLQPKTKGESANCEKYGKVIPAS
  AVIFGMAVECAEIRRHHRVGIKDIAGIHLPTNVKFQSPAYSSVDTEETIEPYTTEKMSRV
  PGGYLALTECFEIMTVDFNNLQELKSLATKKPDKIGIPVIKEGILDAIMVWFVLQLDDEH
  SLSTSPSEETCWEQAVYPVQDLADYWIKPGDHVMMEVSCQDCYLRIQSISVLGLECEMDV
  AKSFTQNKDLLSLGNEAELCSALANLQTSKPDAVEQTCILESTEIALLNNIPYHEGFKMA
  MSKVLSSLTPEKLYQTMDTHCQNEMSSGTGQSNTVQNILEPFYVLDVSEGFSVLPVIAGT
  LGQVKPYSSVEKDQHRIALDLISEANHFPKETLEFWLRHVEDESAMLQRPKSDKLWSIII
  LDVIEPSGLIQQEIMEKAAISRCLLQSGGKIFPQYVLMFGLLVESQTLLEENAVQGTERT
  LGLNIAPFINQFQVPIRVFLDLSSLPCIPLSKPVELLRLDLMTPYLNTSNREVKVYVCKS
  GRLTAIPFWYHMYLDEEIRLDTSSEASHWKQAAVVLDNPIQVEMGEELVLSIQHHKSNVS
  ITVKQ
• 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.
• BioCyc Pathway: MetaCyc:ENSG00000164169-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[1]
Hepatitis B virus infection	DISLQ2XY	Limited	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	DISJZ467	Limited	Autosomal recessive	[3]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[1]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein arginine N-methyltransferase 9 (PRMT9).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein arginine N-methyltransferase 9 (PRMT9).	[5]

References

• [1] MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1 protein.Oncotarget. 2017 Jan 10;8(2):2342-2355. doi: 10.18632/oncotarget.13672.
• [2] PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK-3/Snail signaling.Cancer Sci. 2018 May;109(5):1414-1427. doi: 10.1111/cas.13598.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.