Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT80XOJB)

• DOT Name: Class A basic helix-loop-helix protein 9 (BHLHA9)
• Synonyms: bHLHa9; Class F basic helix-loop-helix factor 42; bHLHf42
• Gene Name: BHLHA9
• Related Disease:
  Split hand-foot malformation 1 with sensorineural hearing loss
  Congenital deformities of limbs
  Hemimelia
  Mesoaxial synostotic syndactyly with phalangeal reduction
  Polydactyly
  Split hand-foot malformation
  Camptosynpolydactyly, complex
  Split-hand/foot malformation with long bone deficiency 1
  Syndactyly
• UniProt ID: BHA09_HUMAN
• Pfam ID: PF00010
• Sequence:
  MLRGAPGLGLTARKGAEDSAEDLGGPCPEPGGDSGVLGANGASCSRGEAEEPAGRRRARP
  VRSKARRMAANVRERKRILDYNEAFNALRRALRHDLGGKRLSKIATLRRAIHRIAALSLV
  LRASPAPRGPCGHLECHGPAARGDTGDTGASPPPPAGPSLARPDAARPSVPSAPRCASCP
  PHAPLARPSAVAEGPGLAQASGGSWRRCPGASSAGPPPWPRGYLRSAPGMGHPRS
• Function: Transcription factor, which play a role in limb development. Is an essential player in the regulatory network governing transcription of genes implicated in limb morphogenesis.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Split hand-foot malformation 1 with sensorineural hearing loss	DISEHK38	Definitive	Autosomal dominant	[1]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[2]
Hemimelia	DIS6GPFJ	Strong	Genetic Variation	[1]
Mesoaxial synostotic syndactyly with phalangeal reduction	DIS3IXR5	Strong	Autosomal recessive	[3]
Polydactyly	DIS25BMZ	Strong	Genetic Variation	[4]
Split hand-foot malformation	DIS8PKGD	Strong	Biomarker	[2]
Camptosynpolydactyly, complex	DISDUJB9	Limited	Autosomal recessive	[5]
Split-hand/foot malformation with long bone deficiency 1	DISF5YQK	Limited	Unknown	[3]
Syndactyly	DISZK2BT	Limited	Genetic Variation	[4]

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 Class A basic helix-loop-helix protein 9 (BHLHA9).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Class A basic helix-loop-helix protein 9 (BHLHA9).	[7]

References

• [1] Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion. J Med Genet. 2012 Feb;49(2):119-25. doi: 10.1136/jmedgenet-2011-100409. Epub 2011 Dec 6.
• [2] Gene dosage of the transcription factor Fingerin (bHLHA9) affects digit development and links syndactyly to ectrodactyly.Hum Mol Genet. 2014 Oct 15;23(20):5394-401. doi: 10.1093/hmg/ddu257. Epub 2014 May 22.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] A novel insertion and deletion mutation in the BHLHA9 underlies polydactyly and mesoaxial synostotic syndactyly with phalangeal reduction.Eur J Med Genet. 2019 Apr;62(4):278-281. doi: 10.1016/j.ejmg.2018.08.005. Epub 2018 Aug 11.
• [5] Complex Camptosynpolydactyly and Mesoaxial synostotic syndactyly with phalangeal reduction are allelic disorders. Am J Med Genet A. 2016 Jun;170(6):1622-5. doi: 10.1002/ajmg.a.37643. Epub 2016 Apr 4.
• [6] 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.
• [7] 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.