Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9V0ZBY)

• DOT Name: Leucine-rich repeat-containing protein 10 (LRRC10)
• Gene Name: LRRC10
• Related Disease:
  Dilated cardiomyopathy 1A
  Atrial fibrillation
  Familial atrial fibrillation
  Arrhythmia
  Brugada syndrome
  Cardiomyopathy
  Dilated cardiomyopathy
• UniProt ID: LRC10_HUMAN
• Pfam ID: PF13855
• Sequence:
  MGNTIRALVAFIPADRCQNYVVRDLREMPLDKMVDLSGSQLRRFPLHVCSFRELVKLYLS
  DNHLNSLPPELGQLQNLQILALDFNNFKALPQVVCTLKQLCILYLGNNKLCDLPSELSLL
  QNLRTLWIEANCLTQLPDVVCELSLLKTLHAGSNALRLLPGQLRRLQELRTIWLSGNRLT
  DFPTVLLHMPFLEVIDVDWNSIRYFPSLAHLSSLKLVIYDHNPCRNAPKVAKGVRRVGRW
  AEETPEPDPRKARRYALVREESQELQAPVPLLPPTNS
• Function: May play important roles in cardiac development and/or cardiac function.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[2]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]
Arrhythmia	DISFF2NI	Limited	Biomarker	[3]
Brugada syndrome	DISSGN0E	Limited	Biomarker	[3]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[3]
Dilated cardiomyopathy	DISX608J	No Known	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Leucine-rich repeat-containing protein 10 (LRRC10).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat-containing protein 10 (LRRC10).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leucine-rich repeat-containing protein 10 (LRRC10).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine-rich repeat-containing protein 10 (LRRC10).	[9]

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 Leucine-rich repeat-containing protein 10 (LRRC10).	[8]

References

• [1] Pediatric Dilated Cardiomyopathy-Associated LRRC10 (Leucine-Rich Repeat-Containing 10) Variant Reveals LRRC10 as an Auxiliary Subunit of Cardiac L-Type Ca(2+) Channels.J Am Heart Assoc. 2018 Feb 3;7(3):e006428. doi: 10.1161/JAHA.117.006428.
• [2] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [3] Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population.Int J Legal Med. 2017 May;131(3):621-628. doi: 10.1007/s00414-016-1516-z. Epub 2016 Dec 28.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] 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.