Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHK0PS4)

• DOT Name: Dynein axonemal intermediate chain 2 (DNAI2)
• Synonyms: Axonemal dynein intermediate chain 2
• Gene Name: DNAI2
• Related Disease:
  Primary ciliary dyskinesia 9
  Acute otitis media
  B-cell neoplasm
  Disseminated intravascular coagulation
  Male infertility
  Primary ciliary dyskinesia
• UniProt ID: DNAI2_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00400
• Sequence:
  MEIVYVYVKKRSEFGKQCNFSDRQAELNIDIMPNPELAEQFVERNPVDTGIQCSISMSEH
  EANSERFEMETRGVNHVEGGWPKDVNPLELEQTIRFRKKVEKDENYVNAIMQLGSIMEHC
  IKQNNAIDIYEEYFNDEEAMEVMEEDPSAKTINVFRDPQEIKRAATHLSWHPDGNRKLAV
  AYSCLDFQRAPVGMSSDSYIWDLENPNKPELALKPSSPLVTLEFNPKDSHVLLGGCYNGQ
  IACWDTRKGSLVAELSTIESSHRDPVYGTIWLQSKTGTECFSASTDGQVMWWDIRKMSEP
  TEVVILDITKKEQLENALGAISLEFESTLPTKFMVGTEQGIVISCNRKAKTSAEKIVCTF
  PGHHGPIYALQRNPFYPKNFLTVGDWTARIWSEDSRESSIMWTKYHMAYLTDAAWSPVRP
  TVFFTTRMDGTLDIWDFMFEQCDPTLSLKVCDEALFCLRVQDNGCLIACGSQLGTTTLLE
  VSPGLSTLQRNEKNVASSMFERETRREKILEARHREMRLKEKGKAEGRDEEQTDEELAVD
  LEALVSKAEEEFFDIIFAELKKKEADAIKLTPVPQQPSPEEDQVVEEGEEAAGEEGDEEV
  EEDLA
• Function: Part of the dynein complex of respiratory cilia.
• Tissue Specificity: Highly expressed in trachea and testis. Expressed in respiratory ciliated cells (at protein level) .
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 9	DISUMJM1	Definitive	Autosomal recessive	[1]
Acute otitis media	DISL8D8G	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Disseminated intravascular coagulation	DISCAVOZ	moderate	Biomarker	[4]
Male infertility	DISY3YZZ	moderate	Altered Expression	[3]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dynein axonemal intermediate chain 2 (DNAI2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dynein axonemal intermediate chain 2 (DNAI2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dynein axonemal intermediate chain 2 (DNAI2).	[10]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dynein axonemal intermediate chain 2 (DNAI2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Dynein axonemal intermediate chain 2 (DNAI2).	[9]

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] The Role of the Notch Signal Pathway in Mucosal Cell Metaplasia in Mouse Acute Otitis Media.Sci Rep. 2017 Jul 4;7(1):4588. doi: 10.1038/s41598-017-04639-z.
• [3] Dynein axonemal intermediate chain 2 plays a role in gametogenesis by activation of Stat3.J Cell Mol Med. 2019 Jan;23(1):417-425. doi: 10.1111/jcmm.13945. Epub 2018 Nov 1.
• [4] Activation of the coagulation cascade in patients with scrub typhus.Diagn Microbiol Infect Dis. 2017 Sep;89(1):1-6. doi: 10.1016/j.diagmicrobio.2017.06.011. Epub 2017 Jun 19.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.