Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAIQ6V6)

• DOT Name: Transmembrane and coiled-coil domain protein 3 (TMCC3)
• Gene Name: TMCC3
• Related Disease: Small lymphocytic lymphoma
• UniProt ID: TMCC3_HUMAN
• Pfam ID: PF10267
• Sequence:
  MPGSDTALTVDRTYSYPGRHHRCKSRVERHDMNTLSLPLNIRRGGSDTNLNFDVPDGILD
  FHKVKLTADSLKQKILKVTEQIKIEQTSRDGNVAEYLKLVNNADKQQAGRIKQVFEKKNQ
  KSAHSIAQLQKKLEQYHRKLREIEQNGASRSSKDISKDHLKDIHRSLKDAHVKSRTAPHC
  MESSKSGMPGVSLTPPVFVFNKSREFANLIRNKFGSADNIAHLKNSLEEFRPEASARAYG
  GSATIVNKPKYGSDDECSSGTSGSADSNGNQSFGAGGASTLDSQGKLAVILEELREIKDT
  QAQLAEDIEALKVQFKREYGFISQTLQEERYRYERLEDQLHDLTDLHQHETANLKQELAS
  IEEKVAYQAYERSRDIQEALESCQTRISKLELHQQEQQALQTDTVNAKVLLGRCINVILA
  FMTVILVCVSTIAKFVSPMMKSRCHILGTFFAVTLLAIFCKNWDHILCAIERMIIPR
• Tissue Specificity: Widely expressed, with highest levels in brain, spinal cord and testis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[1]

16 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 Transmembrane and coiled-coil domain protein 3 (TMCC3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[4]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[6]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[7]
Bleomycin	DMNER5S	Approved	Bleomycin decreases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[5]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[9]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transmembrane and coiled-coil domain protein 3 (TMCC3).	[10]

References

• [1] Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation.Mol Cell Proteomics. 2018 Apr;17(4):776-791. doi: 10.1074/mcp.RA117.000539. Epub 2018 Jan 24.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] 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.
• [6] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [7] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [8] 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.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] 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.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.