Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTODFO9P)

• DOT Name: Homeobox and leucine zipper protein Homez (HOMEZ)
• Synonyms: Homeodomain leucine zipper-containing factor
• Gene Name: HOMEZ
• Related Disease: Ventricular septal defect
• UniProt ID: HOMEZ_HUMAN
• PDB ID: 2ECC; 2YS9
• Pfam ID: PF11569
• Sequence:
  MVRGWEPPPGLDCAISEGHKSEGTMPPNKEASGLSSSPAGLICLPPISEELQLVWTQAAQ
  TSELDSNEHLLKTFSYFPYPSLADIALLCLRYGLQMEKVKTWFMAQRLRCGISWSSEEIE
  ETRARVVYRRDQLHFKSLLSFTHHAGRPPEEVPPPPVPAPEQVGIGIGPPTLSKPTQTKG
  LKVEPEEPSQMPPLPQSHQKLKESLMTPGSGAFPYQSDFWQHLQSSGLSKEQAGRGPNQS
  HGIGTASWNHSTTVPQPQARDKPPPIALIASSCKEESASSVTPSSSSTSSSFQVLANGAT
  AASKPLQPLGCVPQSVSPSEQALPPHLEPAWPQGLRHNSVPGRVGPTEYLSPDMQRQRKT
  KRKTKEQLAILKSFFLQCQWARREDYQKLEQITGLPRPEIIQWFGDTRYALKHGQLKWFR
  DNAVPGAPSFQDPAIPTPPPSTRSLNERAETPPLPIPPPPPDIQPLERYWAAHQQLRETD
  IPQLSQASRLSTQQVLDWFDSRLPQPAEVVVCLDEEEEEEEEELPEDDEEEEEEEEEDDD
  DDDDDVIIQD
• Function: May function as a transcriptional regulator.
• Tissue Specificity: Ubiquitous. Strongly expressed in adult testis and kidney as well as fetal lung and kidney.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ventricular septal defect	DISICO41	Strong	Genetic Variation	[1]

7 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 Homeobox and leucine zipper protein Homez (HOMEZ).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homeobox and leucine zipper protein Homez (HOMEZ).	[8]

References

• [1] Identification of two novel mutations of the HOMEZ gene in Chinese patients with isolated ventricular septal defect.Genet Test Mol Biomarkers. 2013 May;17(5):390-4. doi: 10.1089/gtmb.2012.0435. Epub 2013 Apr 10.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.