Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFPK182)

• DOT Name: Transmembrane and coiled-coil domain-containing protein 4 (TMCO4)
• Gene Name: TMCO4
• Related Disease: Isolated cleft lip
• UniProt ID: TMCO4_HUMAN
• Pfam ID: PF05277
• Sequence:
  MAMWNRPCQRLPQQPLVAEPTAEGEPHLPTGRELTEANRFAYAALCGISLSQLFPEPEHS
  SFCTEFMAGLVQWLELSEAVLPTMTAFASGLGGEGADVFVQILLKDPILKDDPTVITQDL
  LSFSLKDGHYDARARVLVCHMTSLLQVPLEELDVLEEMFLESLKEIKEEESEMAEASRKK
  KENRRKWKRYLLIGLATVGGGTVIGVTGGLAAPLVAAGAATIIGSAGAAALGSAAGIAIM
  TSLFGAAGAGLTGYKMKKRVGAIEEFTFLPLTEGRQLHITIAVTGWLASGKYRTFSAPWA
  ALAHSREQYCLAWEAKYLMELGNALETILSGLANMVAQEALKYTVLSGIVAALTWPASLL
  SVANVIDNPWGVCLHRSAEVGKHLAHILLSRQQGRRPVTLIGFSLGARVIYFCLQEMAQE
  KDCQGIIEDVILLGAPVEGEAKHWEPFRKVVSGRIINGYCRGDWLLSFVYRTSSVQLRVA
  GLQPVLLQDRRVENVDLTSVVSGHLDYAKQMDAILKAVGIRTKPGWDEKGLLLAPGCLPS
  EEPRQAAAAASSGETPHQVGQTQGPISGDTSKLAMSTDPSQAQVPVGLDQSEGASLPAAA
  SPERPPICSHGMDPNPLGCPDCACKTQGPSTGLD

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[1]

5 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-containing protein 4 (TMCO4).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane and coiled-coil domain-containing protein 4 (TMCO4).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane and coiled-coil domain-containing protein 4 (TMCO4).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane and coiled-coil domain-containing protein 4 (TMCO4).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane and coiled-coil domain-containing protein 4 (TMCO4).	[7]

1 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-containing protein 4 (TMCO4).	[6]

References

• [1] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.