Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT505E7T)

• DOT Name: Sodium channel modifier 1 (SCNM1)
• Gene Name: SCNM1
• Related Disease:
  Dystonia
  Orofaciodigital syndrome 19
  Nervous system disease
• UniProt ID: SCNM1_HUMAN
• PDB ID: 7DVQ
• Pfam ID: PF15805 ; PF15803
• Sequence:
  MSFKREGDDWSQLNVLKKRRVGDLLASYIPEDEALMLRDGRFACAICPHRPVLDTLAMLT
  AHRAGKKHLSSLQLFYGKKQPGKERKQNPKHQNELRREETKAEAPLLTQTRLITQSALHR
  APHYNSCCRRKYRPEAPGPSVSLSPMPPSEVKLQSGKISREPEPAAGPQAEESATVSAPA
  PMSPTRRRALDHYLTLRSSGWIPDGRGRWVKDENVEFDSDEEEPPDLPLD
• Function: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Plays a role in the regulation of primary cilia length and Hedgehog signaling.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dystonia	DISJLFGW	Strong	Biomarker	[1]
Orofaciodigital syndrome 19	DISJ4JUS	Strong	Autosomal recessive	[2]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sodium channel modifier 1 (SCNM1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium channel modifier 1 (SCNM1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sodium channel modifier 1 (SCNM1).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sodium channel modifier 1 (SCNM1).	[8]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium channel modifier 1 (SCNM1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sodium channel modifier 1 (SCNM1).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Sodium channel modifier 1 (SCNM1).	[10]

References

• [1] Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.Hum Mol Genet. 1999 Mar;8(3):471-9. doi: 10.1093/hmg/8.3.471.
• [2] Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia. Am J Hum Genet. 2022 Oct 6;109(10):1828-1849. doi: 10.1016/j.ajhg.2022.08.009. Epub 2022 Sep 8.
• [3] High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot.Genomics. 2003 Oct;82(4):452-9. doi: 10.1016/s0888-7543(03)00152-6.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.