Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLFL6K8)

• DOT Name: Neurogenic differentiation factor 6 (NEUROD6)
• Synonyms: NeuroD6; Class A basic helix-loop-helix protein 2; bHLHa2; Protein atonal homolog 2
• Gene Name: NEUROD6
• Related Disease:
  Alzheimer disease
  Acute myelogenous leukaemia
  Advanced cancer
  Lewy body dementia
  Parkinson disease
• UniProt ID: NDF6_HUMAN
• Pfam ID: PF00010 ; PF12533
• Sequence:
  MLTLPFDESVVMPESQMCRKFSRECEDQKQIKKPESFSKQIVLRGKSIKRAPGEETEKEE
  EEEDREEEDENGLPRRRGLRKKKTTKLRLERVKFRRQEANARERNRMHGLNDALDNLRKV
  VPCYSKTQKLSKIETLRLAKNYIWALSEILRIGKRPDLLTFVQNLCKGLSQPTTNLVAGC
  LQLNARSFLMGQGGEAAHHTRSPYSTFYPPYHSPELTTPPGHGTLDNSKSMKPYNYCSAY
  ESFYESTSPECASPQFEGPLSPPPINYNGIFSLKQEETLDYGKNYNYGMHYCAVPPRGPL
  GQGAMFRLPTDSHFPYDLHLRSQSLTMQDELNAVFHN
• Function: Activates E box-dependent transcription in collaboration with TCF3/E47. May be a trans-acting factor involved in the development and maintenance of the mammalian nervous system. Transactivates the promoter of its own gene.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Lewy body dementia	DISAE66J	Limited	Biomarker	[4]
Parkinson disease	DISQVHKL	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Neurogenic differentiation factor 6 (NEUROD6).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neurogenic differentiation factor 6 (NEUROD6).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neurogenic differentiation factor 6 (NEUROD6).	[6]

References

• [1] Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.Sci Rep. 2015 Sep 23;5:14324. doi: 10.1038/srep14324.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.Neuropsychopharmacology. 2017 Dec;42(13):2516-2526. doi: 10.1038/npp.2017.91. Epub 2017 May 4.
• [4] Differential -synuclein expression contributes to selective vulnerability of hippocampal neuron subpopulations to fibril-induced toxicity.Acta Neuropathol. 2018 Jun;135(6):855-875. doi: 10.1007/s00401-018-1829-8. Epub 2018 Mar 3.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] 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.
• [7] 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.