Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA3QKKG)

• DOT Name: Bone morphogenetic protein 10 (BMP10)
• Synonyms: BMP-10
• Gene Name: BMP10
• Related Disease:
  Congenital heart disease
  Left ventricular noncompaction
  Pulmonary arterial hypertension
• UniProt ID: BMP10_HUMAN
• PDB ID: 6SF1; 6SF3; 7PPA; 7PPB; 7PPC
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MGSLVLTLCALFCLAAYLVSGSPIMNLEQSPLEEDMSLFGDVFSEQDGVDFNTLLQSMKD
  EFLKTLNLSDIPTQDSAKVDPPEYMLELYNKFATDRTSMPSANIIRSFKNEDLFSQPVSF
  NGLRKYPLLFNVSIPHHEEVIMAELRLYTLVQRDRMIYDGVDRKITIFEVLESKGDNEGE
  RNMLVLVSGEIYGTNSEWETFDVTDAIRRWQKSGSSTHQLEVHIESKHDEAEDASSGRLE
  IDTSAQNKHNPLLIVFSDDQSSDKERKEELNEMISHEQLPELDNLGLDSFSSGPGEEALL
  QMRSNIIYDSTARIRRNAKGNYCKRTPLYIDFKEIGWDSWIIAPPGYEAYECRGVCNYPL
  AEHLTPTKHAIIQALVHLKNSQKASKACCVPTKLEPISILYLDKGVVTYKFKYEGMAVSE
  CGCR
• Function: Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.
• Tissue Specificity: Detected in mammary epithelia (at protein level).
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  Signaling by BMP (R-HSA-201451)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital heart disease	DISQBA23	Limited	Autosomal dominant	[1]
Left ventricular noncompaction	DISJ4QEG	Limited	Autosomal dominant	[2]
Pulmonary arterial hypertension	DISP8ZX5	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoproterenol	DMK7MEY	Approved	Bone morphogenetic protein 10 (BMP10) decreases the response to substance of Isoproterenol.	[5]

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 decreases the methylation of Bone morphogenetic protein 10 (BMP10).	[3]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Bone morphogenetic protein 10 (BMP10).	[4]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] 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.
• [3] 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.
• [4] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.
• [5] BMP10 preserves cardiac function through its dual activation of SMAD-mediated and STAT3-mediated pathways. J Biol Chem. 2019 Dec 27;294(52):19877-19888. doi: 10.1074/jbc.RA119.010943. Epub 2019 Nov 11.