Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHLBM3Z)

• DOT Name: Ankyrin repeat domain-containing protein 18A (ANKRD18A)
• Gene Name: ANKRD18A
• Related Disease:
  Lung cancer
  Lung carcinoma
  Lung neoplasm
• UniProt ID: AN18A_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF14915 ; PF12001
• Sequence:
  MRKLFSFGRRLGQALLSSMDQEYAGPGYDIRDWELRKIHRAAIKGDAAEVERCLTRRFRD
  LDARDRKDRTVLHLACAHGRVQVVTLLLHRRCQIDICDRLNRTPLMKAVHSQEEACAIVL
  LECGANPNIEDIYGNTALHYAVYNKGTSLAERLLSHHANIEALNKEGNTPLLFAINSRRQ
  HMVEFLLKNQANIHAVDNFKRTALILAVQHNLSSIVTLLLQQNIRISSQDMFGQTAEDYA
  LCSDLRSIRQQILEHKNKMLKNHLRNDNQETAAMKPANLKKRKERAKAEHNLKVASEEKQ
  ERLQRSENKQPQDSQSYGKKKDAMYGNFMLKKDIAMLKEELYAIKNDSLRKEKKYIQEIK
  SITEINANFEKSVRLNEKMITKTVARYSQQLNDLKAENARLNSELEKEKHNKERLEAEVE
  SLHSSLATAINEYNEIVERKDLELVLWRADDVSRHEKMGSNISQLTDKNELLTEQVHKAR
  VKFNTLKGKLRETRDALREKTLALGSVQLDLRQAQHRIKEMKQMHPNGEAKESQSIGKQN
  SLEERIRQQELENLLLERQLEDARKEGDNKEIVINIHRDCLENGKEDLLEERNKELMKEY
  NYLKEKLLQCEKEKAEREVIVREFQEELVDHLKTFSISESPLEGTSHCHINLNETWTSKK
  KLFQVEIQPEEKHEEFRKLFELISLLNYTADQIRKKNRELEEEATGYKKCLEMTINMLNA
  FANEDFSCHGDLNTDQLKMDILFKKLKQKFNDLVAEKEAVSSECVNLAKDNEVLHQELLS
  MRNVQEKCEKLEKDKKMLEEEVLNLKTHMEKDMVELGKLQEYKSELDERAVQEIEKLEEI
  HLQKQAEYEKQLEQLNKDNTASLKKKELTLKDVECKFSKMKTAYEEVTTELEEFKEAFAG
  AVKANNSMSKKLMKSDKKIAVISTKLFTEKQRMKYFLSTLPTRPEPELPCVENLNSIELN
  RKYIPKTAIRIPTSNPQTSNNCKNFLTEVLLC

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A).	[9]

References

• [1] ANKRD18A as a novel epigenetic regulation gene in lung cancer.Biochem Biophys Res Commun. 2012 Dec 14;429(3-4):180-5. doi: 10.1016/j.bbrc.2012.10.116. Epub 2012 Nov 3.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
• [9] 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.