Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDXNK54)

• DOT Name: Leucine-rich repeat-containing protein 56 (LRRC56)
• Gene Name: LRRC56
• Related Disease:
  Ciliary dyskinesia, primary, 39
  Ciliopathy
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia
• UniProt ID: LRC56_HUMAN
• Pfam ID: PF12799
• Sequence:
  MDLGWDRSRGPRRSTSSVRVRELSWQGLHNPCPQSKGPGSQRDRLGEQLVEEYLSPARLQ
  ALARVDDLRLVRTLEMCVDTREGSLGNFGVHLPNLDQLKLNGSHLGSLRDLGTSLGHLQV
  LWLARCGLADLDGIASLPALKELYASYNNISDLSPLCLLEQLEVLDLEGNSVEDLGQVRY
  LQLCPRLAMLTLEGNLVCLQPAPGPTNKVPRGYNYRAEVRKLIPQLQVLDEVPAAHTGPP
  APPRLSQDWLAVKEAIKKGNGLPPLDCPRGAPIRRLDPELSLPETQSRASRPWPFSLLVR
  GGPLPEGLLSEDLAPEDNTSSLTHGAGQVLCGNPTKGLRERRHQCQAREPPEQLPQHRPG
  DPAASTSTPEPDPADSSDFLALAGLRAWREHGVRPLPYRHPESQQEGAVAPWGPRRVPEE
  QVHQAEPKTPSSPPSLASEPSGTSSQHLVPSPPKHPRPRDSGSSSPRWSTDLQSRGRRLR
  VLGSWGPGLGDGVAAVPVLRALEVASRLSPRAQGCPGPKPAPDAAARPPRAAELSHPSPV
  PT
• Function: Required for the assembly of dynein arms.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliary dyskinesia, primary, 39	DISPJM44	Strong	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Strong	Biomarker	[2]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[2]

3 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 Leucine-rich repeat-containing protein 56 (LRRC56).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich repeat-containing protein 56 (LRRC56).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Leucine-rich repeat-containing protein 56 (LRRC56).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Leucine-rich repeat-containing protein 56 (LRRC56).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leucine-rich repeat-containing protein 56 (LRRC56).	[7]

References

• [1] [Improvement of working conditions and reduction of the incidence of occupational diseases among workers engaged in mechanical handling of crystal glass]. Gig Tr Prof Zabol. 1978 Feb;(2):48-50.
• [2] Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects. Am J Hum Genet. 2018 Nov 1;103(5):727-739. doi: 10.1016/j.ajhg.2018.10.003.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [6] 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.
• [7] 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.