Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTRI3KI)

• DOT Name: Homeobox protein Hox-A13 (HOXA13)
• Synonyms: Homeobox protein Hox-1J
• Gene Name: HOXA13
• Related Disease:
  Hand-foot-genital syndrome
  Guttmacher syndrome
• UniProt ID: HXA13_HUMAN
• PDB ID: 2L7Z
• Pfam ID: PF00046 ; PF12284
• Sequence:
  MTASVLLHPRWIEPTVMFLYDNGGGLVADELNKNMEGAAAAAAAAAAAAAAGAGGGGFPH
  PAAAAAGGNFSVAAAAAAAAAAAANQCRNLMAHPAPLAPGAASAYSSAPGEAPPSAAAAA
  AAAAAAAAAAAAASSSGGPGPAGPAGAEAAKQCSPCSAAAQSSSGPAALPYGYFGSGYYP
  CARMGPHPNAIKSCAQPASAAAAAAFADKYMDTAGPAAEEFSSRAKEFAFYHQGYAAGPY
  HHHQPMPGYLDMPVVPGLGGPGESRHEPLGLPMESYQPWALPNGWNGQMYCPKEQAQPPH
  LWKSTLPDVVSHPSDASSYRRGRKKRVPYTKVQLKELEREYATNKFITKDKRRRISATTN
  LSERQVTIWFQNRRVKEKKVINKLKTTS
• Function: Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.; 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hand-foot-genital syndrome	DISZQ3U9	Definitive	Autosomal dominant	[1]
Guttmacher syndrome	DIS2U14Y	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Homeobox protein Hox-A13 (HOXA13).	[3]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Homeobox protein Hox-A13 (HOXA13).	[5]

1 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 decreases the methylation of Homeobox protein Hox-A13 (HOXA13).	[4]

References

• [1] Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Genet. 2000 Jul;67(1):197-202. doi: 10.1086/302961. Epub 2000 Jun 5.
• [2] A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome. Hum Mutat. 2002 May;19(5):573-4. doi: 10.1002/humu.9036.
• [3] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [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] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.