Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCYGL4F)

• DOT Name: LETM1 domain-containing protein LETM2, mitochondrial (LETM2)
• Synonyms: LETM1 and EF-hand domain-containing protein 2; Leucine zipper-EF-hand-containing transmembrane protein 1-like
• Gene Name: LETM2
• Related Disease:
  Esophageal squamous cell carcinoma
  Schizophrenia
• UniProt ID: LETM2_HUMAN
• Pfam ID: PF07766 ; PF19324
• Sequence:
  MAFYSYNSVLAIARTRFPSHFVHPTCSSYSPSCAFLHLPDSHLNKTCMKNYESKKYSDPS
  QPGNTVLHPGTRLIQKLHTSTCWLQEVPGKPQLEQATKHPQVTSPQATKETGMEIKEGKQ
  SYRQKIMDELKYYYNGFYLLWIDAKVAARMVWRLLHGQVLTRRERRRLLRTCVDFFRLVP
  FMVFLIVPFMEFLLPVFLKLFPEMLPSTFESESKKEEKQKKKMAVKLELAKFLQETMTEM
  ARRNRAKMGDASTQLSSYVKQVQTGHKPSTKEIVRFSKLFEDQLALEHLDRPQLVALCKL
  LELQTFGTNNLLRFQLLMKLKSIKADDEIIAKEGVTALSVSELQAACRARGMRSLGLTEE
  QLRQQLTEWQDLHLKENVPPSLLLLSRTFYLIDVKPKPIEIPLSGEAPKTDILVELPTFT
  ESKENMVDLAPQLKGTKDEDFIQPPPVTSSPITPSTPISLPKGPITSSEEPTLQAKSQMT
  AQNSKASSKGA

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]

8 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 LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[7]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of LETM1 domain-containing protein LETM2, mitochondrial (LETM2).	[8]

References

• [1] Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma.Am J Hum Genet. 2016 Feb 4;98(2):256-74. doi: 10.1016/j.ajhg.2015.12.013. Epub 2016 Jan 28.
• [2] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.