Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLBB4DJ)

• DOT Name: ELMO domain-containing protein 3 (ELMOD3)
• Synonyms: RNA-binding motif and ELMO domain-containing protein 1; RNA-binding motif protein 29; RNA-binding protein 29
• Gene Name: ELMOD3
• Related Disease:
  Deafness
  Pervasive developmental disorder
  Atrial septal defect
  Autosomal recessive nonsyndromic hearing loss 88
  Intellectual disability
  Hearing loss, autosomal recessive
  Autism spectrum disorder
  Nonsyndromic genetic hearing loss
• UniProt ID: ELMD3_HUMAN
• Pfam ID: PF04727
• Sequence:
  MNEKSCSFHSKEELRDGQGERLSAGYSPSYDKDKSVLAFRGIPISELKNHGILQALTTEA
  YEWEPRVVSTEVVRAQEEWEAVDTIQPETGSQASSEQPGQLISFSEALQHFQTVDLSPFK
  KRIQPTIRRTGLAALRHYLFGPPKLHQRLREERDLVLTIAQCGLDSQDPVHGRVLQTIYK
  KLTGSKFDCALHGNHWEDLGFQGANPATDLRGAGFLALLHLLYLVMDSKTLPMAQEIFRL
  SRHHIQQFPFCLMSVNITHIAIQALREECLSRECNRQQKVIPVVNSFYAATFLHLAHVWR
  TQRKTISDSGFVLKELEVLAKKSPRRLLKTLELYLARVSKGQASLLGAQKCYGPEAPPFK
  DLTFTGESDLQSHSSEGVWLI
• Function: Acts as a GTPase-activating protein (GAP) for ARL2 with low specific activity.
• Tissue Specificity: Both isoform 1 and isoform 6 are widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness	DISKCLH4	Strong	Biomarker	[1]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[2]
Atrial septal defect	DISJT76B	moderate	Biomarker	[1]
Autosomal recessive nonsyndromic hearing loss 88	DISXY86L	Moderate	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[1]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[3]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[2]
Nonsyndromic genetic hearing loss	DISZX61P	Limited	Autosomal dominant	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ELMO domain-containing protein 3 (ELMOD3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ELMO domain-containing protein 3 (ELMOD3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ELMO domain-containing protein 3 (ELMOD3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ELMO domain-containing protein 3 (ELMOD3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of ELMO domain-containing protein 3 (ELMOD3).	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of ELMO domain-containing protein 3 (ELMOD3).	[10]

References

• [1] Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology.J Appl Genet. 2019 Feb;60(1):49-56. doi: 10.1007/s13353-018-0472-3. Epub 2018 Oct 4.
• [2] ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario.J Cell Mol Med. 2020 Jan;24(2):2064-2069. doi: 10.1111/jcmm.14733. Epub 2019 Dec 4.
• [3] An alteration in ELMOD3, an Arl2 GTPase-activating protein, is associated with hearing impairment in humans. PLoS Genet. 2013;9(9):e1003774. doi: 10.1371/journal.pgen.1003774. Epub 2013 Sep 5.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.