Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGG9BJS)

• DOT Name: Homeobox protein Hox-C12 (HOXC12)
• Synonyms: Homeobox protein Hox-3F
• Gene Name: HOXC12
• Related Disease:
  Clubfoot
  Congenital vertical talus
  Hydatidiform mole
• UniProt ID: HXC12_HUMAN
• Pfam ID: PF00046
• Sequence:
  MGEHNLLNPGFVGPLVNIHTGDTFYFPNFRASGAQLPGLPSLSYPRRDNVCSLSWPSAEP
  CNGYPQPYLGSPVSLNPPFGRTCELARVEDGKGYYREPCAEGGGGGLKREERGRDPGAGP
  GAALLPLEPSGPPALGFKYDYAAGGGGGDGGGGAGPPHDPPSCQSLESDSSSSLLNEGNK
  GAGAGDPGSLVSPLNPGGGLSASGAPWYPINSRSRKKRKPYSKLQLAELEGEFLVNEFIT
  RQRRRELSDRLNLSDQQVKIWFQNRRMKKKRLLLREQALSFF
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clubfoot	DISLXT4S	Strong	Genetic Variation	[1]
Congenital vertical talus	DISZF3HD	Strong	Genetic Variation	[1]
Hydatidiform mole	DISKNP7O	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Homeobox protein Hox-C12 (HOXC12).	[3]

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 affects the methylation of Homeobox protein Hox-C12 (HOXC12).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Homeobox protein Hox-C12 (HOXC12).	[5]

References

• [1] Deletions of 5' HOXC genes are associated with lower extremity malformations, including clubfoot and vertical talus.J Med Genet. 2016 Apr;53(4):250-5. doi: 10.1136/jmedgenet-2015-103505. Epub 2016 Jan 4.
• [2] The three most downstream genes of the Hox-3 cluster are expressed in human extraembryonic tissues including trophoblast of androgenetic origin.Development. 1990 Mar;108(3):471-7. doi: 10.1242/dev.108.3.471.
• [3] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [4] 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.
• [5] 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.