Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8OMCFD)

• DOT Name: NALCN channel auxiliary factor 1 (NALF1)
• Synonyms: Transmembrane protein FAM155A
• Gene Name: NALF1
• UniProt ID: NALF1_HUMAN
• PDB ID: 6XIW; 7CM3; 7SX3; 7SX4; 7WJI
• Sequence:
  MTRGAWMCRQYDDGLKIWLAAPRENEKPFIDSERAQKWRLSLASLLFFTVLLSDHLWFCA
  EAKLTRARDKEHQQQQRQQQQQQQQQRQRQQQQQQRRQQEPSWPALLASMGESSPAAQAH
  RLLSASSSPTLPPSPGDGGGGGGKGNRGKDDRGKALFLGNSAKPVWRLETCYPQGASSGQ
  CFTVENADAVCARNWSRGAAGGDGQEVRSKHPTPLWNLSDFYLSFCNSYTLWELFSGLSS
  PNTLNCSLDVVLKEGGEMTTCRQCVEAYQDYDHHAQEKYEEFESVLHKYLQSEEYSVKSC
  PEDCKIVYKAWLCSQYFEVTQFNCRKTIPCKQYCLEVQTRCPFILPDNDEVIYGGLSSFI
  CTGLYETFLTNDEPECCDVRREEKSNNPSKGTVEKSGSCHRTSLTVSSATRLCNSRLKLC
  VLVLILLHTVLTASAAQNTAGLSFGGINTLEENSTNEE
• Function: Auxillary component of the NALCN sodium channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of NALCN channel auxiliary factor 1 (NALF1).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of NALCN channel auxiliary factor 1 (NALF1).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of NALCN channel auxiliary factor 1 (NALF1).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of NALCN channel auxiliary factor 1 (NALF1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of NALCN channel auxiliary factor 1 (NALF1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of NALCN channel auxiliary factor 1 (NALF1).	[7]

2 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 NALCN channel auxiliary factor 1 (NALF1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of NALCN channel auxiliary factor 1 (NALF1).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] 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.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.