Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ZKCRS)

• DOT Name: Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9)
• Synonyms: EC 2.3.1.308; Embryo brain-specific protein
• Gene Name: NAT9
• Related Disease:
  Crohn disease
  Atopic dermatitis
  Epidermolysis bullosa simplex 1A, generalized severe
  Epidermolysis bullosa simplex 2E, with migratory circinate erythema
  Epidermolysis bullosa simplex 2F, with mottled pigmentation
  Epidermolysis bullosa simplex 5B, with muscular dystrophy
  Melanoma
  Mental disorder
  Muscular dystrophy
  Psoriasis
  Skin disease
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Epidermolysis bullosa simplex
  Prune belly syndrome
• UniProt ID: NAT9_HUMAN
• EC Number: 2.3.1.308
• Pfam ID: PF13302
• Sequence:
  MRLNQNTLLLGKKVVLVPYTSEHVPSRYHEWMKSEELQRLTASEPLTLEQEYAMQCSWQE
  DADKCTFIVLDAEKWQAQPGATEESCMVGDVNLFLTDLEDLTLGEIEVMIAEPSCRGKGL
  GTEAVLAMLSYGVTTLGLTKFEAKIGQGNEPSIRMFQKLHFEQVATSSVFQEVTLRLTVS
  ESEHQWLLEQTSHVEEKPYRDGSAEPC
• Function: N-acetyltransferase that mediates the acetylation of the N-terminal residues of alpha- and beta-tubulin.
• BioCyc Pathway: MetaCyc:ENSG00000109065-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[1]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[2]
Epidermolysis bullosa simplex 1A, generalized severe	DISD362G	Strong	Genetic Variation	[3]
Epidermolysis bullosa simplex 2E, with migratory circinate erythema	DIS4EGXJ	Strong	Genetic Variation	[4]
Epidermolysis bullosa simplex 2F, with mottled pigmentation	DIS7VDBV	Strong	Genetic Variation	[5]
Epidermolysis bullosa simplex 5B, with muscular dystrophy	DIS739SC	Strong	Genetic Variation	[6]
Melanoma	DIS1RRCY	Strong	Biomarker	[7]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[8]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[9]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[1]
Skin disease	DISDW8R6	Strong	Genetic Variation	[3]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[10]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[10]
Epidermolysis bullosa simplex	DIS2CZ6X	Limited	Genetic Variation	[11]
Prune belly syndrome	DISBIBMN	Limited	Biomarker	[12]

5 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 Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9).	[15]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Alpha/beta-tubulin-N-acetyltransferase 9 (NAT9).	[17]

References

• [1] Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study.Circ Cardiovasc Genet. 2009 Apr;2(2):134-41. doi: 10.1161/CIRCGENETICS.108.825273. Epub 2009 Feb 12.
• [2] Investigation of the chromosome 17q25 PSORS2 locus in atopic dermatitis.J Invest Dermatol. 2006 Mar;126(3):603-6. doi: 10.1038/sj.jid.5700108.
• [3] An exvivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex.Br J Dermatol. 2019 Jan;180(1):141-148. doi: 10.1111/bjd.17075. Epub 2018 Oct 7.
• [4] T-lymphocytes are directly involved in the clinical expression of migratory circinate erythema in epidermolysis bullosa simplex patients.Acta Derm Venereol. 2014 May;94(3):307-11. doi: 10.2340/00015555-1691.
• [5] Epidermolysis bullosa simplex with mottled pigmentation - mutation analysis proved the diagnosis in a four-generation pedigree.Eur J Dermatol. 2010 Nov-Dec;20(6):698-700. doi: 10.1684/ejd.2010.1080. Epub 2010 Oct 5.
• [6] Compound heterozygous PLEC mutations in a patient of consanguineous parentage with epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia.Int J Dermatol. 2015 Feb;54(2):185-7. doi: 10.1111/ijd.12655. Epub 2014 Sep 10.
• [7] Sensitivity of human melanoma cells to oestrogens, tamoxifen and quercetin: is there any relationship with type I and II oestrogen binding site expression?.Melanoma Res. 1998 Aug;8(4):313-22. doi: 10.1097/00008390-199808000-00004.
• [8] The 2014 Ontario Child Health Study Emotional Behavioural Scales (OCHS-EBS) Part II: Psychometric Adequacy for Categorical Measurement of Selected DSM-5 Disorders.Can J Psychiatry. 2019 Jun;64(6):434-442. doi: 10.1177/0706743718808251. Epub 2018 Oct 30.
• [9] Immunofluorescence analysis of villous trophoblasts: a tool for prenatal diagnosis of inherited epidermolysis bullosa with pyloric atresia.J Invest Dermatol. 2008 Dec;128(12):2815-9. doi: 10.1038/jid.2008.143. Epub 2008 Jun 19.
• [10] Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: growth inhibitory effect of oestrogen and flavonoids.Br J Haematol. 1990 Aug;75(4):489-95. doi: 10.1111/j.1365-2141.1990.tb07787.x.
• [11] Epidermolysis bullosa simplex with mottled pigmentation: a family report and review.Pediatr Dermatol. 2013 Nov-Dec;30(6):e125-31. doi: 10.1111/j.1525-1470.2012.01748.x. Epub 2012 May 29.
• [12] Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.Pediatr Transplant. 2018 Mar;22(2). doi: 10.1111/petr.13123. Epub 2018 Jan 22.
• [13] 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.
• [14] 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.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.