Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRU3EOK)

• DOT Name: BTB/POZ domain-containing protein KCTD7 (KCTD7)
• Gene Name: KCTD7
• Related Disease:
  Progressive myoclonic epilepsy type 3
  Progressive myoclonus epilepsy
  Unverricht-Lundborg syndrome
  Epilepsy
  Epilepsy, progressive myoclonic, 1B
  Movement disorder
  Neuronal ceroid lipofuscinosis
  Advanced cancer
  Bipolar disorder
  Obesity
  Schizophrenia
  Lysosomal storage disease
  Stroke
• UniProt ID: KCTD7_HUMAN
• Pfam ID: PF02214
• Sequence:
  MVVVTGREPDSRRQDGAMSSSDAEDDFLEPATPTATQAGHALPLLPQEFPEVVPLNIGGA
  HFTTRLSTLRCYEDTMLAAMFSGRHYIPTDSEGRYFIDRDGTHFGDVLNFLRSGDLPPRE
  RVRAVYKEAQYYAIGPLLEQLENMQPLKGEKVRQAFLGLMPYYKDHLERIVEIARLRAVQ
  RKARFAKLKVCVFKEEMPITPYECPLLNSLRFERSESDGQLFEHHCEVDVSFGPWEAVAD
  VYDLLHCLVTDLSAQGLTVDHQCIGVCDKHLVNHYYCKRPIYEFKITWW
• Function: May be involved in the control of excitability of cortical neurons.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive myoclonic epilepsy type 3	DISK80V8	Definitive	Autosomal recessive	[1]
Progressive myoclonus epilepsy	DISAMCNS	Definitive	Autosomal recessive	[2]
Unverricht-Lundborg syndrome	DISG4WLX	Definitive	Biomarker	[3]
Epilepsy	DISBB28L	Strong	Genetic Variation	[3]
Epilepsy, progressive myoclonic, 1B	DISZDF43	Strong	Genetic Variation	[4]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[5]
Neuronal ceroid lipofuscinosis	DIS9A4K4	Strong	Genetic Variation	[6]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Bipolar disorder	DISAM7J2	moderate	Biomarker	[5]
Obesity	DIS47Y1K	moderate	Genetic Variation	[5]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[5]
Lysosomal storage disease	DIS6QM6U	Limited	Genetic Variation	[7]
Stroke	DISX6UHX	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BTB/POZ domain-containing protein KCTD7 (KCTD7).	[12]

References

• [1] Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. Ann Neurol. 2007 Jun;61(6):579-86. doi: 10.1002/ana.21121.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Exome sequencing identifies compound heterozygous KCTD7 mutations in a girl with progressivemyoclonus epilepsy.Clin Chim Acta. 2019 Jun;493:87-91. doi: 10.1016/j.cca.2019.02.028. Epub 2019 Feb 28.
• [4] Linkage analysis and exome sequencing identify a novel mutation in KCTD7 in patients with progressive myoclonus epilepsy with ataxia.Epilepsia. 2014 Sep;55(9):e106-11. doi: 10.1111/epi.12730. Epub 2014 Jul 24.
• [5] KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders.CNS Neurosci Ther. 2019 Jul;25(7):887-902. doi: 10.1111/cns.13156.
• [6] Progressive myoclonus epilepsy and ceroidolipofuscinosis 14: The multifaceted phenotypic spectrum of KCTD7-related disorders.Eur J Med Genet. 2019 Dec;62(12):103591. doi: 10.1016/j.ejmg.2018.11.025. Epub 2018 Nov 27.
• [7] KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect.Ann Neurol. 2018 Nov;84(5):766-780. doi: 10.1002/ana.25351. Epub 2018 Nov 8.
• [8] Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AF(RANDOMISED) Trial.Stroke. 2020 Feb;51(2):395-401. doi: 10.1161/STROKEAHA.119.026496. Epub 2019 Dec 9.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] 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.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.