Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW00SHB)

• DOT Name: Death domain-containing protein 1 (DTHD1)
• Gene Name: DTHD1
• Related Disease:
  Inherited retinal dystrophy
  Hepatocellular carcinoma
  LCAT deficiency
• UniProt ID: DTHD1_HUMAN
• Pfam ID: PF00531
• Sequence:
  MHDECTPQQTMSSIQDTKAADIAARGELNVIETATVSPTNGEESHYTNQVQLEKNKTHMS
  SALVEKENNTSLNGRVLGQEESQNKMFPDNAENEDDKQIEHMTVENINGNREETHGIIQT
  TETEIQETSESPREEMTTSSIICDISKKYINSTLPNDSENIKHKNNIMEKEYLDVLSDVT
  GPQVSCYITAPSYVLQQLECRIINHMSSLIVGDNEELVSNVITIECSDKEKRVPFPIGIA
  IPFTARYRGNYRDIMVKVCDINLQSSYLNPNSLEGMKGGYKGTCASVKVYKLGIFSVVSC
  LKKESFTVTKKGLALKSSMDSRISLNYPPGVFTSPVLVQLKIQPVDPALVAHLKAQQDTF
  YSVQSTSPLIHIQHPSTYPFQKPVTLFLPCSPYLDKNNLGSEIDHKRRASATINRITPSY
  FNRTKIASIRKPRKNASECLKLLGFRSQDSGWCGLDDVVKTIQSGLVSVELYEHLERFIV
  LHLSSTMDNSHLVTFVKSLEEAMLSTTACIVLSHQKDNPHRIAVLVVPSKDLSQVLKDLH
  LEGFGGPPEPSRHFQVREGEQLLLRFTGNIFASSNGKDYGKDYTLIFHLQRKPRLELQIK
  EVDEFGNYSCPHYKGTIVVYKVPKGKIVPNLNQSLVINENHSQLPICKLPLKLPKHKKLI
  NRPQSTKRVSKDPVEALWDNLLHWLAEELSEENAESLSSTLPLRRSTIQLIKLKNPDDLT
  EQIHEFLCFWKKSLPTFTDKLRLLARHLRKIGRSDLAEELKFKWENKVFTEPQQCFDVAP
  E

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[2]
LCAT deficiency	DISV6DVF	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Death domain-containing protein 1 (DTHD1).	[3]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Death domain-containing protein 1 (DTHD1).	[4]

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 Death domain-containing protein 1 (DTHD1).	[5]

References

• [1] Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res. 2013 Feb;23(2):236-47. doi: 10.1101/gr.144105.112. Epub 2012 Oct 26.
• [2] An indel polymorphism within pre-miR3131 confers risk for hepatocellular carcinoma.Carcinogenesis. 2017 Feb 1;38(2):168-176. doi: 10.1093/carcin/bgw206.
• [3] 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.
• [4] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [5] 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.