Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGSOX3C)

• DOT Name: BTB/POZ domain-containing protein KCTD16 (KCTD16)
• Synonyms: Potassium channel tetramerization domain-containing protein 16
• Gene Name: KCTD16
• Related Disease:
  Encephalitis
  Neoplasm
• UniProt ID: KCD16_HUMAN
• PDB ID: 5A15; 6I0Q; 6M8R; 6OCP; 6OCR; 6OCT; 6QB7
• Pfam ID: PF02214
• Sequence:
  MALSGNCSRYYPREQGSAVPNSFPEVVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRD
  TANDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRLKREAEYFQLPDLVK
  LLTPDEIKQSPDEFCHSDFEDASQGSDTRICPPSSLLPADRKWGFITVGYRGSCTLGREG
  QADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDML
  SECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFYREPSRWSPSHCDCCCKNGKGDKE
  GESGTSCNDLSTSSCDSQSEASSPQETVICGPVTRQTNIQTLDRPIKKGPVQLIQQSEMR
  RKSDLLRTLTSGSRESNMSSKKKAVKEKLSIEEELEKCIQDFLKIKIPDRFPERKHPWQS
  ELLRKYHL
• Function: Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Encephalitis	DISLD1RL	moderate	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BTB/POZ domain-containing protein KCTD16 (KCTD16).	[2]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of BTB/POZ domain-containing protein KCTD16 (KCTD16).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BTB/POZ domain-containing protein KCTD16 (KCTD16).	[5]

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 BTB/POZ domain-containing protein KCTD16 (KCTD16).	[4]

References

• [1] The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies.Brain. 2019 Jun 1;142(6):1631-1643. doi: 10.1093/brain/awz094.
• [2] 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.
• [3] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [4] 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.
• [5] 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.