Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU5AWIS)

• DOT Name: Dynein axonemal light chain 1 (DNAL1)
• Synonyms: LC1
• Gene Name: DNAL1
• Related Disease:
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia 16
  Primary ciliary dyskinesia
• UniProt ID: DNAL1_HUMAN
• PDB ID: 8J07
• Pfam ID: PF12799
• Sequence:
  MAKATTIKEALARWEEKTGQRPSEAKEIKLYAQIPPIEKMDASLSMLANCEKLSLSTNCI
  EKIANLNGLKNLRILSLGRNNIKNLNGLEAVGDTLEELWISYNFIEKLKGIHIMKKLKIL
  YMSNNLVKDWAEFVKLAELPCLEDLVFVGNPLEEKHSAENNWIEEATKRVPKLKKLDGTP
  VIKGDEEEDN
• Function: Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency. Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme. Important for ciliary function in the airways and for the function of the cilia that produce the nodal flow essential for the determination of the left-right asymmetry.
• Tissue Specificity: Expressed in tissues carrying motile cilia such as respiratory epithelia, ependyma and testis.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 1	DISPGX6H	Strong	CausalMutation	[1]
Primary ciliary dyskinesia 16	DIS1LLRC	Strong	Autosomal recessive	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[3]

1 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 Dynein axonemal light chain 1 (DNAL1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dynein axonemal light chain 1 (DNAL1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dynein axonemal light chain 1 (DNAL1).	[6]

References

• [1] Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am J Hum Genet. 2011 May 13;88(5):599-607. doi: 10.1016/j.ajhg.2011.03.018. Epub 2011 Apr 14.
• [2] Co-detection of chimeric bcr/abl (target) and beta-actin (control) messenger RNA in individual CFU-GM colonies derived from CML patients using the polymerase chain reaction. Leuk Res. 1991;15(9):867-74. doi: 10.1016/0145-2126(91)90471-5.
• [3] Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.