Details of Drug Off-Target (DOT)

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

• DOT Name: Coiled-coil domain-containing protein 154 (CCDC154)
• Gene Name: CCDC154
• Related Disease:
  Autosomal recessive osteopetrosis 1
  Parkinson disease
  Neoplasm
  Osteopetrosis
• UniProt ID: CC154_HUMAN
• Pfam ID: PF15450
• Sequence:
  MSELADSGPSGASAPSQLRAVTLEDLGLLLAGGLASPEPLSLEELSERYESSHPTSTASV
  PEQDTAKHWNQLEQWVVELQAEVACLREHKQRCERATRSLLRELLQVRARVQLQGSELRQ
  LQQEARPAAQAPEKEAPEFSGLQNQMQALDKRLVEVREALTRLRRRQVQQEAERRGAEQE
  AGLRLAKLTDLLQQEEQGREVACGALQKNQEDSSRRVDLEVARMQAQVTKLGEEVSLRFL
  KREAKLCGFLQKSFLALEKRMKASESSRLKLEGSLRGELESRWEKLRGLMEERLRALQGQ
  HEESHLLEQCQGLDAAVAQLTKFVQQNQASLNRVLLAEEKAWDAKGRLEESRAGELAAYV
  QENLEAAQLAGELARQEMHGELVLLREKSRALEASVAQLAGQLKELSGHLPALSSRLDLQ
  EQMLGLRLSEAKTEWEGAERKSLEDLARWRKEVTEHLRGVREKVDGLPQQIESVSDKCLL
  HKSDSDLRISAEGKAREFKVGALRQELATLLSSVQLLKEDNPGRKIAEMQGKLATFQNQI
  MKLENCVQANKTIQNLRFNTEARLRTQEMATLWESVLRLWSEEGPRTPLGSWKALPSLVR
  PRVFIKDMAPGKVVPMNCWGVYQAVRWLRWKASLIKLRALRRPGGVLEKPHSQEQVQQLT
  PSLFIQK

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive osteopetrosis 1	DISU8DQM	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]
Osteopetrosis	DIS7GHNM	Limited	Biomarker	[3]

3 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 Coiled-coil domain-containing protein 154 (CCDC154).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coiled-coil domain-containing protein 154 (CCDC154).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Coiled-coil domain-containing protein 154 (CCDC154).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[7]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[8]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coiled-coil domain-containing protein 154 (CCDC154).	[10]

References

• [1] A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots.Eur J Oral Sci. 2009 Dec;117(6):625-35. doi: 10.1111/j.1600-0722.2009.00690.x.
• [2] Proteomics and bioinformatics approaches for the identification of plasma biomarkers to detect Parkinson's disease.Exp Ther Med. 2019 Oct;18(4):2833-2842. doi: 10.3892/etm.2019.7888. Epub 2019 Aug 14.
• [3] Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest.Cell Cycle. 2012 Sep 1;11(17):3270-9. doi: 10.4161/cc.21642. Epub 2012 Aug 16.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [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] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.