Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7Z1422)

• DOT Name: BEN domain-containing protein 4 (BEND4)
• Synonyms: Coiled-coil domain-containing protein 4
• Gene Name: BEND4
• Related Disease:
  Major depressive disorder
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: BEND4_HUMAN
• Pfam ID: PF10523
• Sequence:
  MEEEMQPAEEGPSVPKIYKQRSPYSVLKTFPSKRPALAKRYERPTLVELPHVRAPPPPPP
  PFAPHAAVSISSSEPPPQQFQAQSSYPPGPGRAAAAASSSSPSCTPATSQGHLRTPAQPP
  PASPAASSSSSFAAVVRYGPGAAAAAGTGGTGSDSASLELSAESRMILDAFAQQCSRVLS
  LLNCGGKLLDSNHSQSMISCVKQEGSSYNERQEHCHIGKGVHSQTSDNVDIEMQYMQRKQ
  QTSAFLRVFTDSLQNYLLSGSFPTPNPSSASEYGHLADVDPLSTSPVHTLGGWTSPATSE
  SHGHPSSSTLPEEEEEEDEEGYCPRCQELEQEVISLQQENEELRRKLESIPVPCQTVLDY
  LKMVLQHHNQLLIPQPADQPTEGSKQLLNNYPVYITSKQWDEAVNSSKKDGRRLLRYLIR
  FVFTTDELKYSCGLGKRKRSVQSGETGPERRPLDPVKVTCLREFIRMHCTSNPDWWMPSE
  EQINKVFSDAVGHARQGRAVGTFLHNGGSFYEGIDHQASQDEVFNKSSQDGSGD

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Disputed	Posttranslational Modification	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]

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 BEN domain-containing protein 4 (BEND4).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of BEN domain-containing protein 4 (BEND4).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BEN domain-containing protein 4 (BEND4).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of BEN domain-containing protein 4 (BEND4).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of BEN domain-containing protein 4 (BEND4).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BEN domain-containing protein 4 (BEND4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of BEN domain-containing protein 4 (BEND4).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of BEN domain-containing protein 4 (BEND4).	[10]

References

• [1] Identification of common genetic risk variants for autism spectrum disorder.Nat Genet. 2019 Mar;51(3):431-444. doi: 10.1038/s41588-019-0344-8. Epub 2019 Feb 25.
• [2] Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning.Endocr Relat Cancer. 2011 Jul 4;18(4):465-78. doi: 10.1530/ERC-11-0083. Print 2011 Aug.
• [3] Asbestos-associated genome-wide DNA methylation changes in lung cancer.Int J Cancer. 2017 Nov 15;141(10):2014-2029. doi: 10.1002/ijc.30897. Epub 2017 Aug 2.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [9] 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.
• [10] 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.