Details of Drug Off-Target (DOT)

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

• DOT Name: Neurogenic differentiation factor 4 (NEUROD4)
• Synonyms: NeuroD4; Class A basic helix-loop-helix protein 4; bHLHa4; Protein atonal homolog 3; ATH-3; Atoh3
• Gene Name: NEUROD4
• Related Disease:
  Maturity-onset diabetes of the young
  Pineoblastoma
  Lung neoplasm
  Myelitis
  Neuroendocrine neoplasm
  Small-cell lung cancer
• UniProt ID: NDF4_HUMAN
• Pfam ID: PF00010 ; PF12533
• Sequence:
  MSKTFVKSKEMGELVNTPSWMDKGLGSQNEVKEEESRPGTYGMLSSLTEEHDSIEEEEEE
  EEDGEKPKRRGPKKKKMTKARLERFRARRVKANARERTRMHGLNDALDNLRRVMPCYSKT
  QKLSKIETLRLARNYIWALSEVLETGQTPEGKGFVEMLCKGLSQPTSNLVAGCLQLGPQS
  VLLEKHEDKSPICDSAISVHNFNYQSPGLPSPPYGHMETHLLHLKPQVFKSLGESSFGSH
  LPDCSTPPYEGPLTPPLSISGNFSLKQDGSPDLEKSYSFMPHYPSSSLSSGHVHSTPFQA
  GTPRYDVPIDMSYDSYPHHGIGTQLNTVFTE
• Function: Probably acts as a transcriptional activator. Mediates neuronal differentiation. Required for the regulation of amacrine cell fate specification in the retina.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Maturity-onset diabetes of the young	DISG75M5	Strong	Genetic Variation	[1]
Pineoblastoma	DISQK8F3	Strong	Biomarker	[2]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[3]
Myelitis	DIS1KV65	Limited	Biomarker	[4]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[3]
Small-cell lung cancer	DISK3LZD	Limited	Altered Expression	[3]

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 decreases the methylation of Neurogenic differentiation factor 4 (NEUROD4).	[5]

References

• [1] beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.Diabetes. 2000 Nov;49(11):1955-7. doi: 10.2337/diabetes.49.11.1955.
• [2] Molecular characterization of central neurocytomas: potential markers for tumor typing and progression.Neuropathology. 2013 Apr;33(2):149-61. doi: 10.1111/j.1440-1789.2012.01338.x. Epub 2012 Jul 23.
• [3] Basic helix-loop-helix transcription factor profiling of lung tumors shows aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1) in neuroendocrine tumors.Int J Biol Markers. 2007 Apr-Jun;22(2):114-23. doi: 10.1177/172460080702200205.
• [4] MiR-137 attenuates spinal cord injury by modulating NEUROD4 through reducing inflammation and oxidative stress.Eur Rev Med Pharmacol Sci. 2018 Apr;22(7):1884-1890. doi: 10.26355/eurrev_201804_14709.
• [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.