Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0WRVJC)

• DOT Name: ELMO domain-containing protein 1 (ELMOD1)
• Gene Name: ELMOD1
• Related Disease:
  Autism spectrum disorder
  Intellectual disability
  Pervasive developmental disorder
• UniProt ID: ELMD1_HUMAN
• Pfam ID: PF04727
• Sequence:
  MKHFLRMLIQVCLYFYCKFLWRCLKFVMRKLTGRCELQRICYNTKPGASRTMKIETSLRD
  SKSKLLQTSVSVHPDAIEKTIEDIMELKKINPDVNPQLGISLQACLLQIVGYRNLIADVE
  KLRREAYDSDNPQHEEMLLKLWKFLKPNTPLESRISKQWCEIGFQGDDPKTDFRGMGLLG
  LYNLQYFAERDATAAQQVLSDSLHPKCRDITKEEISKFSKAEWEKKRMDKAIGYSFAIVG
  INITDLAYNLLVSGALKTHFYNIAPEAPTLSHFQQTFCYLMHEFHKFWIEEDPMDIMEFN
  RVREKFRKRIIKQLQNPDMALCPHFAASEGLINM
• Function: Acts as a GTPase-activating protein (GAP) toward guanine nucleotide exchange factors like ARL2, ARL3, ARF1 and ARF6, but not for GTPases outside the Arf family.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ELMO domain-containing protein 1 (ELMOD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of ELMO domain-containing protein 1 (ELMOD1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ELMO domain-containing protein 1 (ELMOD1).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of ELMO domain-containing protein 1 (ELMOD1).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of ELMO domain-containing protein 1 (ELMOD1).	[14]

2 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 ELMO domain-containing protein 1 (ELMOD1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of ELMO domain-containing protein 1 (ELMOD1).	[10]

References

• [1] ELMO Domain Containing 1 (ELMOD1) Gene Mutation Is Associated with Mental Retardation and Autism Spectrum Disorder.J Mol Neurosci. 2019 Oct;69(2):312-315. doi: 10.1007/s12031-019-01359-z. Epub 2019 Jul 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.