Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJYTQ69)

• DOT Name: Biotinidase (BTD)
• Synonyms: Biotinase; EC 3.5.1.12
• Gene Name: BTD
• Related Disease:
  Biotinidase deficiency
  Acute coronary syndrome
  Advanced cancer
  Autism
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Congestive heart failure
  Disorder of glycogen metabolism
  Gerstmann-Straussler-Scheinker syndrome
  Glycogen storage disease due to GLUT2 deficiency
  Glycogen storage disease I
  Hepatitis B virus infection
  Holocarboxylase synthetase deficiency
  Intestinal disorder
  Metabolic disorder
  Multiple carboxylase deficiency
  Myelopathy
  Psoriasis
  Sensorineural hearing loss disorder
  West syndrome
  Leigh syndrome
  Biotin metabolic disease
• UniProt ID: BTD_HUMAN
• EC Number: 3.5.1.12
• Pfam ID: PF00795 ; PF19018
• Sequence:
  MAHAHIQGGRRAKSRFVVCIMSGARSKLALFLCGCYVVALGAHTGEESVADHHEAEYYVA
  AVYEHPSILSLNPLALISRQEALELMNQNLDIYEQQVMTAAQKDVQIIVFPEDGIHGFNF
  TRTSIYPFLDFMPSPQVVRWNPCLEPHRFNDTEVLQRLSCMAIRGDMFLVANLGTKEPCH
  SSDPRCPKDGRYQFNTNVVFSNNGTLVDRYRKHNLYFEAAFDVPLKVDLITFDTPFAGRF
  GIFTCFDILFFDPAIRVLRDYKVKHVVYPTAWMNQLPLLAAIEIQKAFAVAFGINVLAAN
  VHHPVLGMTGSGIHTPLESFWYHDMENPKSHLIIAQVAKNPVGLIGAENATGETDPSHSK
  FLKILSGDPYCEKDAQEVHCDEATKWNVNAPPTFHSEMMYDNFTLVPVWGKEGYLHVCSN
  GLCCYLLYERPTLSKELYALGVFDGLHTVHGTYYIQVCALVRCGGLGFDTCGQEITEATG
  IFEFHLWGNFSTSYIFPLFLTSGMTLEVPDQLGWENDHYFLRKSRLSSGLVTAALYGRLY
  ERD
• Function: Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.
• KEGG Pathway:
  Biotin metabolism (hsa00780)
  Metabolic pathways (hsa01100)
  Vitamin digestion and absorption (hsa04977)
• Reactome Pathway:
  Defective BTD causes biotidinase deficiency (R-HSA-3371598)
  Biotin transport and metabolism (R-HSA-196780)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Biotinidase deficiency	DISFHBBV	Definitive	Autosomal recessive	[1]
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Disorder of glycogen metabolism	DISYGNOB	Strong	Altered Expression	[6]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Biomarker	[6]
Glycogen storage disease due to GLUT2 deficiency	DISXRSZ1	Strong	Altered Expression	[7]
Glycogen storage disease I	DISY4Q9T	Strong	Altered Expression	[7]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[8]
Holocarboxylase synthetase deficiency	DISY6SW9	Strong	Biomarker	[9]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[10]
Metabolic disorder	DIS71G5H	Strong	Genetic Variation	[11]
Multiple carboxylase deficiency	DISV3SZX	Strong	Altered Expression	[12]
Myelopathy	DISXV8FG	Strong	Biomarker	[13]
Psoriasis	DIS59VMN	Strong	Altered Expression	[14]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[15]
West syndrome	DISLIAU9	Strong	Altered Expression	[16]
Leigh syndrome	DISWQU45	Moderate	Autosomal recessive	[1]
Biotin metabolic disease	DISX6152	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Biotinidase (BTD).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Biotinidase (BTD).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Biotinidase (BTD).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Biotinidase (BTD).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Biotinidase (BTD).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Biotinidase (BTD).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Biotinidase (BTD).	[23]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Biotinidase (BTD).	[24]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Biotinidase (BTD).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Biotinidase (BTD).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Biotinidase (BTD).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Biotinidase (BTD).	[26]

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] Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.PLoS One. 2017 Jul 28;12(7):e0182115. doi: 10.1371/journal.pone.0182115. eCollection 2017.
• [3] Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker.BMC Cancer. 2010 Mar 26;10:114. doi: 10.1186/1471-2407-10-114.
• [4] A case of partial biotinidase deficiency associated with autism.Child Neuropsychol. 2003 Sep;9(3):184-8. doi: 10.1076/chin.9.3.184.16457.
• [5] Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.Cardiovasc Drugs Ther. 2018 Aug;32(4):373-379. doi: 10.1007/s10557-018-6796-8.
• [6] Evaluation of the biotinidase activity in hepatic glycogen storage disease patients. Undescribed genetic finding associated with atypical enzymatic behavior: an outlook.J Inherit Metab Dis. 2010 Oct;33(Suppl 2):S289-94. doi: 10.1007/s10545-010-9139-x. Epub 2010 Jun 8.
• [7] Elevated serum biotinidase activity in hepatic glycogen storage disorders--a convenient biomarker.J Inherit Metab Dis. 2007 Nov;30(6):896-902. doi: 10.1007/s10545-007-0734-4. Epub 2007 Nov 12.
• [8] Maternal chronic hepatitis B virus does not affect neonatal biotinidase activity.Acta Paediatr. 2008 Mar;97(3):362-5. doi: 10.1111/j.1651-2227.2007.00636.x. Epub 2008 Jan 31.
• [9] Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.Mitochondrion. 2019 Jan;44:58-64. doi: 10.1016/j.mito.2018.01.001. Epub 2018 Jan 4.
• [10] Biotin: overview of the treatment of diseases of cutaneous appendages and of hyperseborrhea.G Ital Dermatol Venereol. 2019 Oct;154(5):557-566. doi: 10.23736/S0392-0488.19.06434-4.
• [11] Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China.Am J Med Genet A. 2018 Mar;176(3):589-596. doi: 10.1002/ajmg.a.38601. Epub 2018 Jan 23.
• [12] Holocarboxylase synthetase deficiency: novel clinical and molecular findings.Clin Genet. 2010 Jul;78(1):88-93. doi: 10.1111/j.1399-0004.2009.01357.x. Epub 2009 Dec 2.
• [13] Profound biotinidase deficiency in a child with predominantly spinal cord disease.J Child Neurol. 2008 Sep;23(9):1043-8. doi: 10.1177/0883073808318062. Epub 2008 Jul 21.
• [14] Proteomic plasma profile of psoriatic patients.J Pharm Biomed Anal. 2018 Jun 5;155:185-193. doi: 10.1016/j.jpba.2018.03.068. Epub 2018 Apr 4.
• [15] Developmental window of sensorineural deafness in biotinidase-deficient mice.J Inherit Metab Dis. 2017 Sep;40(5):733-744. doi: 10.1007/s10545-017-0049-z. Epub 2017 May 17.
• [16] Novel mutation causing partial biotinidase deficiency in a Syrian boy with infantile spasms and retardation.J Child Neurol. 2006 Nov;21(11):978-81. doi: 10.1177/08830738060210110301.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] 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.
• [19] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [20] 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.
• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [23] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [24] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [25] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [26] 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.
• [27] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [28] Chromium(VI) causes down regulation of biotinidase in human bronchial epithelial cells by modifications of histone acetylation. Toxicol Lett. 2011 Aug 28;205(2):140-5. doi: 10.1016/j.toxlet.2011.05.1032. Epub 2011 May 27.