Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAHW9M8)

• DOT Name: Arylsulfatase D (ARSD)
• Synonyms: ASD; EC 3.1.6.-
• Gene Name: ARSD
• Related Disease:
  Cognitive impairment
  Fragile X syndrome
  Adult respiratory distress syndrome
  Aortic valve stenosis
  Atrial septal defect
  Atrioventricular block
  Autoimmune disease
  Bacterial endocarditis
  Breast cancer
  Breast carcinoma
  Cardiac disease
  Cardiac failure
  Cardiovascular disease
  Cerebral palsy
  Chromosomal disorder
  Congestive heart failure
  Cowden disease
  Endometriosis
  Epilepsy
  High blood pressure
  Hypertrophic cardiomyopathy
  Infective endocarditis
  Intellectual disability
  Mental disorder
  Neurodevelopmental disorder
  Nicotine dependence
  Pervasive developmental disorder
  Polycystic ovarian syndrome
  Post-traumatic stress disorder
  Promyelocytic leukaemia
  Ventricular septal defect
  Glaucoma/ocular hypertension
  Immune system disorder
  Language disorder
  Obesity
  OPTN-related open angle glaucoma
  Small lymphocytic lymphoma
  Aorta coarctation
  Acute myelogenous leukaemia
  Asperger syndrome
  Attention deficit hyperactivity disorder
  Cardiomyopathy
  Microphthalmia
  Patent ductus arteriosus
  Rett syndrome
• UniProt ID: ARSD_HUMAN
• EC Number: 3.1.6.-
• Pfam ID: PF00884 ; PF14707
• Sequence:
  MRSAARRGRAAPAARDSLPVLLFLCLLLKTCEPKTANAFKPNILLIMADDLGTGDLGCYG
  NNTLRTPNIDQLAEEGVRLTQHLAAAPLCTPSRAAFLTGRHSFRSGMDASNGYRALQWNA
  GSGGLPENETTFARILQQHGYATGLIGKWHQGVNCASRGDHCHHPLNHGFDYFYGMPFTL
  TNDCDPGRPPEVDAALRAQLWGYTQFLALGILTLAAGQTCGFFSVSARAVTGMAGVGCLF
  FISWYSSFGFVRRWNCILMRNHDVTEQPMVLEKTASLMLKEAVSYIERHKHGPFLLFLSL
  LHVHIPLVTTSAFLGKSQHGLYGDNVEEMDWLIGKVLNAIEDNGLKNSTFTYFTSDHGGH
  LEARDGHSQLGGWNGIYKGGKGMGGWEGGIRVPGIFHWPGVLPAGRVIGEPTSLMDVFPT
  VVQLVGGEVPQDRVIDGHSLVPLLQGAEARSAHEFLFHYCGQHLHAARWHQKDSGSVWKV
  HYTTPQFHPEGAGACYGRGVCPCSGEGVTHHRPPLLFDLSRDPSEARPLTPDSEPLYHAV
  IARVGAAVSEHRQTLSPVPQQFSMSNILWKPWLQPCCGHFPFCSCHEDGDGTP
• Tissue Specificity: Expressed in the pancreas, kidney, liver, lung, placenta, brain and heart.
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  The activation of arylsulfatases (R-HSA-1663150)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Fragile X syndrome	DISE8W3A	Definitive	Biomarker	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Genetic Variation	[3]
Aortic valve stenosis	DISW7AQ9	Strong	Biomarker	[4]
Atrial septal defect	DISJT76B	Strong	Genetic Variation	[5]
Atrioventricular block	DIS8YLE6	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Bacterial endocarditis	DIS920N0	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Cardiac disease	DISVO1I5	Strong	Biomarker	[10]
Cardiac failure	DISDC067	Strong	Biomarker	[11]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[12]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[13]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[14]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[11]
Cowden disease	DISMYKCE	Strong	Biomarker	[15]
Endometriosis	DISX1AG8	Strong	Biomarker	[16]
Epilepsy	DISBB28L	Strong	Biomarker	[17]
High blood pressure	DISY2OHH	Strong	Biomarker	[18]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[19]
Infective endocarditis	DIS88NSA	Strong	Biomarker	[8]
Intellectual disability	DISMBNXP	Strong	Biomarker	[20]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[21]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[22]
Nicotine dependence	DISZD9W7	Strong	Genetic Variation	[23]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[24]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[16]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[25]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[26]
Ventricular septal defect	DISICO41	Strong	Genetic Variation	[27]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Biomarker	[28]
Immune system disorder	DISAEGPH	moderate	Biomarker	[29]
Language disorder	DISTLKP7	moderate	Biomarker	[30]
Obesity	DIS47Y1K	moderate	Biomarker	[31]
OPTN-related open angle glaucoma	DISDR98A	moderate	Genetic Variation	[28]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[32]
Aorta coarctation	DISAFXDJ	Disputed	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[33]
Asperger syndrome	DIS7IBSP	Limited	Biomarker	[34]
Attention deficit hyperactivity disorder	DISL8MX9	Limited	Biomarker	[22]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[35]
Microphthalmia	DISGEBES	Limited	Biomarker	[28]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[36]
Rett syndrome	DISGG5UV	Limited	Biomarker	[37]

16 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 Arylsulfatase D (ARSD).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Arylsulfatase D (ARSD).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Arylsulfatase D (ARSD).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Arylsulfatase D (ARSD).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Arylsulfatase D (ARSD).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Arylsulfatase D (ARSD).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Arylsulfatase D (ARSD).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Arylsulfatase D (ARSD).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Arylsulfatase D (ARSD).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Arylsulfatase D (ARSD).	[47]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Arylsulfatase D (ARSD).	[48]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Arylsulfatase D (ARSD).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Arylsulfatase D (ARSD).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Arylsulfatase D (ARSD).	[51]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Arylsulfatase D (ARSD).	[52]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Arylsulfatase D (ARSD).	[53]

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 Arylsulfatase D (ARSD).	[49]

References

• [1] Do cognitive deficits persist into adolescence in autism?.Autism Res. 2018 Sep;11(9):1229-1238. doi: 10.1002/aur.1976. Epub 2018 Sep 28.
• [2] Language Performance in Preschool-Aged Boys with Nonsyndromic Autism Spectrum Disorder or Fragile X Syndrome.J Autism Dev Disord. 2020 May;50(5):1621-1638. doi: 10.1007/s10803-019-03919-z.
• [3] Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq.PLoS One. 2014 Nov 5;9(11):e111953. doi: 10.1371/journal.pone.0111953. eCollection 2014.
• [4] Association between cardiovascular anomalies and karyotypes in Turner syndrome patients in Taiwan: A local cohort study.Pediatr Neonatol. 2020 Apr;61(2):188-194. doi: 10.1016/j.pedneo.2019.10.001. Epub 2019 Oct 11.
• [5] Adult spinal deformity surgical decision-making score. Part 2: development and validation of a scoring system to guide the selection of treatment modalities for patients above 40years with adult spinal deformity.Eur Spine J. 2020 Jan;29(1):45-53. doi: 10.1007/s00586-019-06068-0. Epub 2019 Jul 17.
• [6] NKX2-5 mutations in an inbred consanguineous population: genetic and phenotypic diversity.Sci Rep. 2015 Mar 6;5:8848. doi: 10.1038/srep08848.
• [7] Association of family history of autoimmune diseases and autism spectrum disorders.Pediatrics. 2009 Aug;124(2):687-94. doi: 10.1542/peds.2008-2445. Epub 2009 Jul 5.
• [8] Infective endocarditis after device closure of atrial septal defects: Case report and review of the literature.Catheter Cardiovasc Interv. 2017 Feb 1;89(2):324-334. doi: 10.1002/ccd.26784. Epub 2016 Sep 19.
• [9] Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study.Psychooncology. 2017 Jan;26(1):74-80. doi: 10.1002/pon.4102. Epub 2016 Feb 22.
• [10] ASD Closure in Structural Heart Disease.Curr Cardiol Rep. 2018 Apr 17;20(6):37. doi: 10.1007/s11886-018-0983-x.
• [11] The promising future of ventricular restraint therapy for the management of end-stage heart failure.Biomed Pharmacother. 2018 Mar;99:25-32. doi: 10.1016/j.biopha.2018.01.003. Epub 2018 Jan 8.
• [12] Outcomes of liver transplantation in pediatric recipients with cardiovascular disease.Pediatr Transplant. 2018 Feb;22(1). doi: 10.1111/petr.13081. Epub 2017 Nov 12.
• [13] Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism.Transl Psychiatry. 2018 Apr 23;8(1):88. doi: 10.1038/s41398-018-0136-4.
• [14] Autism and chromosome abnormalities-A review.Clin Anat. 2016 Jul;29(5):620-7. doi: 10.1002/ca.22719. Epub 2016 Apr 19.
• [15] Clinical presentation of PTEN mutations in childhood in the absence of family history of Cowden syndrome.Eur J Paediatr Neurol. 2015 Mar;19(2):188-92. doi: 10.1016/j.ejpn.2014.11.012. Epub 2014 Dec 16.
• [16] Maternal and Paternal Infertility Disorders and Treatments and Autism Spectrum Disorder: Findings from the Study to Explore Early Development.J Autism Dev Disord. 2017 Dec;47(12):3994-4005. doi: 10.1007/s10803-017-3283-1.
• [17] Why we urgently need improved epilepsy therapies for adult patients.Neuropharmacology. 2020 Jun 15;170:107855. doi: 10.1016/j.neuropharm.2019.107855. Epub 2019 Nov 18.
• [18] Iatrogenic atrial septal defect closure after transseptal mitral valve interventions: Indications and outcomes.Catheter Cardiovasc Interv. 2019 Nov 15;94(6):829-836. doi: 10.1002/ccd.28294. Epub 2019 Apr 19.
• [19] Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.Am J Med Genet A. 2013 Oct;161A(10):2420-30. doi: 10.1002/ajmg.a.36098. Epub 2013 Aug 5.
• [20] Anxiety Disorders in Adults with Autism Spectrum Disorder: A Population-Based Study.J Autism Dev Disord. 2020 Jan;50(1):308-318. doi: 10.1007/s10803-019-04234-3.
• [21] Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders.Cell. 2019 Mar 21;177(1):162-183. doi: 10.1016/j.cell.2019.01.015.
• [22] Association Between Prematurity and Diagnosis of Neurodevelopment Disorder: A Case-Control Study.J Autism Dev Disord. 2020 Jan;50(1):145-152. doi: 10.1007/s10803-019-04235-2.
• [23] Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay. Am J Med Genet B Neuropsychiatr Genet. 2010 Jul;153B(5):983-93. doi: 10.1002/ajmg.b.31064.
• [24] "If He Has it, We Know What to Do": Parent Perspectives on Familial Risk for Autism Spectrum Disorder.J Pediatr Psychol. 2020 Mar 1;45(2):121-130. doi: 10.1093/jpepsy/jsz076.
• [25] The Use of Virtual Reality to Facilitate Mindfulness Skills Training in Dialectical Behavioral Therapy for Spinal Cord Injury: A Case Study.Front Psychol. 2018 Apr 23;9:531. doi: 10.3389/fpsyg.2018.00531. eCollection 2018.
• [26] Cytochemistry of acute promyelocytic leukemia (M3): leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation.Blood. 1985 Aug;66(2):350-7.
• [27] A New Perspective of Migraine Symptoms in Patients With Congenital Heart Defect.Headache. 2018 Nov;58(10):1601-1611. doi: 10.1111/head.13453. Epub 2018 Nov 16.
• [28] Analysis of CYP1B1 in pediatric and adult glaucoma and other ocular phenotypes.Mol Vis. 2016 Oct 17;22:1229-1238. eCollection 2016.
• [29] Frequency of Dendritic Cells and Their Expression of Costimulatory Molecules in Children with Autism Spectrum Disorders.J Autism Dev Disord. 2017 Sep;47(9):2671-2678. doi: 10.1007/s10803-017-3190-5.
• [30] A Spectrotemporal Correlate of Language Impairment in Autism Spectrum Disorder.J Autism Dev Disord. 2019 Aug;49(8):3181-3190. doi: 10.1007/s10803-019-04040-x.
• [31] The risk of overweight and obesity in children with autism spectrum disorders: A systematic review and meta-analysis.Obes Rev. 2019 Dec;20(12):1667-1679. doi: 10.1111/obr.12933. Epub 2019 Oct 8.
• [32] Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.Cancer Biomark. 2011-2012;11(1):15-28. doi: 10.3233/CBM-2012-0259.
• [33] B-lymphoid/myeloid stem cell origin in Ph-positive acute leukemia with myeloid markers.Leuk Res. 1993 Jul;17(7):549-55. doi: 10.1016/0145-2126(93)90083-w.
• [34] Changes in Autism Nosology: The Social Impact of the Removal of Asperger's Disorder from the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5).J Autism Dev Disord. 2020 Sep;50(9):3358-3366. doi: 10.1007/s10803-019-04233-4.
• [35] Clinical features in a girl with Duchenne muscular dystrophy with an X-autosome translocation; (X;4)(p21;q26).Brain Dev. 1986;8(6):619-23. doi: 10.1016/s0387-7604(86)80010-9.
• [36] Congenital heart defects are rarely caused by mutations in cardiac and smooth muscle actin genes.Biomed Res Int. 2015;2015:127807. doi: 10.1155/2015/127807. Epub 2015 Mar 10.
• [37] A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.Cell. 2010 Nov 12;143(4):527-39. doi: 10.1016/j.cell.2010.10.016.
• [38] 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.
• [39] 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.
• [40] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [41] 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.
• [42] 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.
• [43] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [44] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [45] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [46] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [47] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [48] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [49] 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.
• [50] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [51] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [52] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [53] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.