Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZE4XV7)

• DOT Name: Probable inactive allantoicase (ALLC)
• Synonyms: Allantoate amidinohydrolase
• Gene Name: ALLC
• Related Disease:
  Alcohol dependence
  Angioimmunoblastic T-cell Lymphoma
  Dental caries
  Liver cirrhosis
  Melanoma
  Mixed anxiety and depressive disorder
  Non-alcoholic fatty liver disease
  Asthma
  Small lymphocytic lymphoma
  Neoplasm
  Adult lymphoma
  Anxiety
  Anxiety disorder
  Classic Hodgkin lymphoma
  Lymphoma
  Pediatric lymphoma
• UniProt ID: ALLC_HUMAN
• Pfam ID: PF03561
• Sequence:
  MDMASESVGGKILFATDDFFAPAENLIKSDSPCFKEHEYTEFGKWMDGWETRRKRIPGHD
  WCVLRLGIQGVIRGFDVDVSYFTGDYAPRVSIQAANLEEDKLPEIPERGTRTGAAATPEE
  FEAIAELKSDDWSYLVPMTELKPGNPASGHNYFLVNSQQRWTHIRLNIFPDGGIARLRVF
  GTGQKDWTATDPKEPADLVAIAFGGVCVGFSNAKFGHPNNIIGVGGAKSMADGWETARRL
  DRPPILENDENGILLVPGCEWAVFRLAHPGVITRIEIDTKYFEGNAPDSCKVDGCILTTQ
  EEEAVIRQKWILPAHKWKPLLPVTKLSPNQSHLFDSLTLELQDVITHARLTIVPDGGVSR
  LRLRGFPSSICLLRPREKPMLKFSVSFKANP
• Function: The function of this enzyme is unclear as allantoicase activity is not known to exist in mammals.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[1]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Strong	Genetic Variation	[2]
Dental caries	DISRBCMD	Strong	Genetic Variation	[3]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[4]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[6]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[4]
Asthma	DISW9QNS	moderate	Biomarker	[7]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[8]
Neoplasm	DISZKGEW	Disputed	Biomarker	[9]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[10]
Anxiety	DISIJDBA	Limited	Biomarker	[11]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[11]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Genetic Variation	[12]
Lymphoma	DISN6V4S	Limited	Biomarker	[12]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[10]

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 Probable inactive allantoicase (ALLC).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable inactive allantoicase (ALLC).	[15]

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 Probable inactive allantoicase (ALLC).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable inactive allantoicase (ALLC).	[16]

References

• [1] Association study of DRD2 and MAOA genes with subtyped alcoholism comorbid with bipolar disorder in Han Chinese.Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10;40:144-8. doi: 10.1016/j.pnpbp.2012.09.014. Epub 2012 Oct 5.
• [2] Expression of human recombination activating genes (RAG-1 and RAG-2) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T-type.Br J Haematol. 1993 Apr;83(4):655-9. doi: 10.1111/j.1365-2141.1993.tb04706.x.
• [3] Consortium-based genome-wide meta-analysis for childhood dental caries traits.Hum Mol Genet. 2018 Sep 1;27(17):3113-3127. doi: 10.1093/hmg/ddy237.
• [4] Noninvasive characterization of graft steatosis after liver transplantation.Scand J Gastroenterol. 2015 Feb;50(2):224-32. doi: 10.3109/00365521.2014.983156. Epub 2014 Nov 27.
• [5] Redirecting mouse T hybridoma against human breast and ovarian carcinomas: in vivo activity against HER-2/neu expressing cancer cells.Br J Cancer. 2003 Apr 22;88(8):1292-300. doi: 10.1038/sj.bjc.6600888.
• [6] The relationship between serotonin receptor 1B polymorphisms A-161T and alcohol dependence.Alcohol Clin Exp Res. 2009 Sep;33(9):1589-95. doi: 10.1111/j.1530-0277.2009.00990.x. Epub 2009 Jun 10.
• [7] Genome-wide association study identifies ALLC polymorphisms correlated with FEV?change by corticosteroid.Clin Chim Acta. 2014 Sep 25;436:20-6. doi: 10.1016/j.cca.2014.04.023. Epub 2014 May 2.
• [8] B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome.Blood. 2009 Apr 30;113(18):4188-96. doi: 10.1182/blood-2008-09-176149. Epub 2008 Nov 17.
• [9] Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties.J Immunol. 2008 Jul 1;181(1):146-54. doi: 10.4049/jimmunol.181.1.146.
• [10] Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization.Blood. 1989 Aug 1;74(2):810-6.
• [11] MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence.Alcohol Clin Exp Res. 2010 Jul;34(7):1212-8. doi: 10.1111/j.1530-0277.2010.01198.x. Epub 2010 May 7.
• [12] High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large-cell KI-1-positive lymphomas in HIV-1-positive patients.Int J Cancer. 1993 Apr 22;54(1):53-9. doi: 10.1002/ijc.2910540110.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.