Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD5YFW2)

• DOT Name: Myosin-binding protein H-like (MYBPHL)
• Gene Name: MYBPHL
• Related Disease: Familial dilated cardiomyopathy
• UniProt ID: MBPHL_HUMAN
• Pfam ID: PF00041 ; PF07679
• Sequence:
  MEAATAPEVAAGSKLKVKEASPADAEPPQASPGQGAGSPTPQLLPPIEEHPKIWLPRALR
  QTYIRKVGDTVNLLIPFQGKPKPQAIWTHDGCALDTRRVSVRNGEQDSILFIREAQRADS
  GRYQLRVQLGGLEATATIDILVIERPGPPQSIKLVDVWGFSATLEWTPPQDTGNTALLGY
  TVQKADTKSGLWFTVLEHYHRTSCIVSDLIIGNSYAFRVFAENQCGLSETAPITTDLAHI
  QKAATVYKTKGFAQRDFSEAPKFTQPLADCTTVTGYNTQLFCCVRASPRPKIIWLKNKMD
  IQGNPKYRALTHLGICSLEIRKPGPFDGGIYTCKAVNPLGEASVDCRVDVKVPN
• Function: Myosin-binding protein which plays a role in cardiac function. Seems to regulate conduction in the atria and ventricular conduction systems.
• Tissue Specificity: Expressed in heart, with higher expression in the atria.; [Isoform 1]: Expressed in left atrium and ventricle, arteria mammaria interna and skeletal muscle.; [Isoform 2]: Expressed specifically en the left atrium.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial dilated cardiomyopathy	DISBHDU9	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myosin-binding protein H-like (MYBPHL).	[2]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Myosin-binding protein H-like (MYBPHL).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myosin-binding protein H-like (MYBPHL).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myosin-binding protein H-like (MYBPHL).	[6]

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 increases the methylation of Myosin-binding protein H-like (MYBPHL).	[5]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.