Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBRXY6D)

• DOT Name: Homeobox protein HMX2 (HMX2)
• Synonyms: Homeobox protein H6 family member 2
• Gene Name: HMX2
• Related Disease:
  Ear malformation
  Meniere disease
• UniProt ID: HMX2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MGSKEDAGKGCPAAGGVSSFTIQSILGGGPSEAPREPVGWPARKRSLSVSSEEEEPDDGW
  KAPACFCPDQHGPKEQGPKHHPPIPFPCLGTPKGSGGSGPGGLERTPFLSPSHSDFKEEK
  ERLLPAGSPSPGSERPRDGGAERQAGAAKKKTRTVFSRSQVYQLESTFDMKRYLSSSERA
  CLASSLQLTETQVKTWFQNRRNKWKRQLSAELEAANMAHASAQTLVSMPLVFRDSSLLRV
  PVPRSLAFPAPLYYPGSNLSALPLYNLYNKLDY
• Function: Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ear malformation	DISVJGPS	moderate	Genetic Variation	[1]
Meniere disease	DISC5R5F	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Homeobox protein HMX2 (HMX2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein HMX2 (HMX2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Homeobox protein HMX2 (HMX2).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein HMX2 (HMX2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Homeobox protein HMX2 (HMX2).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Homeobox protein HMX2 (HMX2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein HMX2 (HMX2).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Homeobox protein HMX2 (HMX2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Homeobox protein HMX2 (HMX2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homeobox protein HMX2 (HMX2).	[11]

References

• [1] Molecular (SNP) analyses of overlapping hemizygous deletions of 10q25.3 to 10qter in four patients: evidence for HMX2 and HMX3 as candidate genes in hearing and vestibular function.Am J Med Genet A. 2009 Feb 15;149A(4):669-80. doi: 10.1002/ajmg.a.32705.
• [2] Whole-exome sequencing suggests multiallelic inheritance for childhood-onset Mnire's disease.Ann Hum Genet. 2019 Nov;83(6):389-396. doi: 10.1111/ahg.12327. Epub 2019 May 20.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] 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.
• [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] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [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.