Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4EHIP4)

• DOT Name: Ryanodine receptor 3 (RYR3)
• Synonyms: RYR-3; RyR3; Brain ryanodine receptor-calcium release channel; Brain-type ryanodine receptor; Type 3 ryanodine receptor
• Gene Name: RYR3
• Related Disease:
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Glioma
  High blood pressure
  HIV infectious disease
  Myocardial infarction
  Myopathy
  Obsessive compulsive disorder
  Osteoarthritis
  Type-1/2 diabetes
  Hirschsprung disease
  Neuromuscular disease
  Non-hodgkin lymphoma
  Stroke
  Congenital myopathy
  Arteriosclerosis
  Atherosclerosis
  Infantile spasm
• UniProt ID: RYR3_HUMAN
• PDB ID: 4ERV; 6UHA; 6UHB; 6UHE; 6UHH
• Pfam ID: PF08709 ; PF00520 ; PF02815 ; PF08454 ; PF06459 ; PF01365 ; PF21119 ; PF02026 ; PF00622
• Sequence:
  MAEGGEGGEDEIQFLRTEDEVVLQCIATIHKEQRKFCLAAEGLGNRLCFLEPTSEAKYIP
  PDLCVCNFVLEQSLSVRALQEMLANTGENGGEGAAQGGGHRTLLYGHAVLLRHSFSGMYL
  TCLTTSRSQTDKLAFDVGLREHATGEACWWTIHPASKQRSEGEKVRIGDDLILVSVSSER
  YLHLSVSNGNIQVDASFMQTLWNVHPTCSGSSIEEGYLLGGHVVRLFHGHDECLTIPSTD
  QNDSQHRRIFYEAGGAGTRARSLWRVEPLRISWSGSNIRWGQAFRLRHLTTGHYLALTED
  QGLILQDRAKSDTKSTAFSFRASKELKEKLDSSHKRDIEGMGVPEIKYGDSVCFVQHIAS
  GLWVTYKAQDAKTSRLGPLKRKVILHQEGHMDDGLTLQRCQREESQAARIIRNTTALFSQ
  FVSGNNRTAAPITLPIEEVLQTLQDLIAYFQPPEEEMRHEDKQNKLRSLKNRQNLFKEEG
  MLALVLNCIDRLNVYNSVAHFAGIAREESGMAWKEILNLLYKLLAALIRGNRNNCAQFSN
  NLDWLISKLDRLESSSGILEVLHCILTESPEALNLIAEGHIKSIISLLDKHGRNHKVLDI
  LCSLCLCNGVAVRANQNLICDNLLPRRNLLLQTRLINDVTSIRPNIFLGVAEGSAQYKKW
  YFELIIDQVDPFLTAEPTHLRVGWASSSGYAPYPGGGEGWGGNGVGDDLYSYGFDGLHLW
  SGRIPRAVASINQHLLRSDDVVSCCLDLGVPSISFRINGQPVQGMFENFNTDGLFFPVMS
  FSAGVKVRFLMGGRHGEFKFLPPSGYAPCYEALLPKEKMRLEPVKEYKRDADGIRDLLGT
  TQFLSQASFIPCPVDTSQVILPPHLEKIRDRLAENIHELWGMNKIELGWTFGKIRDDNKR
  QHPCLVEFSKLPETEKNYNLQMSTETLKTLLALGCHIAHVNPAAEEDLKKVKLPKNYMMS
  NGYKPAPLDLSDVKLLPPQEILVDKLAENAHNVWAKDRIKQGWTYGIQQDLKNKRNPRLV
  PYALLDERTKKSNRDSLREAVRTFVGYGYNIEPSDQELADSAVEKVSIDKIRFFRVERSY
  AVRSGKWYFEFEVVTGGDMRVGWARPGCRPDVELGADDQAFVFEGNRGQRWHQGSGYFGR
  TWQPGDVVGCMINLDDASMIFTLNGELLITNKGSELAFADYEIENGFVPICCLGLSQIGR
  MNLGTDASTFKFYTMCGLQEGFEPFAVNMNRDVAMWFSKRLPTFVNVPKDHPHIEVMRID
  GTMDSPPCLKVTHKTFGTQNSNADMIYCRLSMPVECHSSFSHSPCLDSEAFQKRKQMQEI
  LSHTTTQCYYAIRIFAGQDPSCVWVGWVTPDYHLYSEKFDLNKNCTVTVTLGDERGRVHE
  SVKRSNCYMVWGGDIVASSQRSNRSNVDLEIGCLVDLAMGMLSFSANGKELGTCYQVEPN
  TKVFPAVFLQPTSTSLFQFELGKLKNAMPLSAAIFRSEEKNPVPQCPPRLDVQTIQPVLW
  SRMPNSFLKVETERVSERHGWVVQCLEPLQMMALHIPEENRCVDILELCEQEDLMRFHYH
  TLRLYSAVCALGNSRVAYALCSHVDLSQLFYAIDNKYLPGLLRSGFYDLLISIHLASAKE
  RKLMMKNEYIIPITSTTRNIRLFPDESKRHGLPGVGLRTCLKPGFRFSTPCFVVTGEDHQ
  KQSPEIPLESLRTKALSMLTEAVQCSGAHIRDPVGGSVEFQFVPVLKLIGTLLVMGVFDD
  DDVRQILLLIDPSVFGEHSAGTEEGAEKEEVTQVEEKAVEAGEKAGKEAPVKGLLQTRLP
  ESVKLQMCELLSYLCDCELQHRVEAIVAFGDIYVSKLQANQKFRYNELMQALNMSAALTA
  RKTKEFRSPPQEQINMLLNFQLGENCPCPEEIREELYDFHEDLLLHCGVPLEEEEEEEED
  TSWTGKLCALVYKIKGPPKPEKEQPTEEEERCPTTLKELISQTMICWAQEDQIQDSELVR
  MMFNLLRRQYDSIGELLQALRKTYTISHTSVSDTINLLAALGQIRSLLSVRMGKEEELLM
  INGLGDIMNNKVFYQHPNLMRVLGMHETVMEVMVNVLGTEKSQIAFPKMVASCCRFLCYF
  CRISRQNQKAMFEHLSYLLENSSVGLASPSMRGSTPLDVAASSVMDNNELALSLEEPDLE
  KVVTYLAGCGLQSCPMLLAKGYPDVGWNPIEGERYLSFLRFAVFVNSESVEENASVVVKL
  LIRRPECFGPALRGEGGNGLLAAMQGAIKISENPALDLPSQGYKREVSTGDDEEEEEIVH
  MGNAIMSFYSALIDLLGRCAPEMHLIQTGKGEAIRIRSILRSLVPTEDLVGIISIPLKLP
  SLNKDGSVSEPDMAANFCPDHKAPMVLFLDRVYGIKDQTFLLHLLEVGFLPDLRASASLD
  TVSLSTTEAALALNRYICSAVLPLLTRCAPLFAGTEHCTSLIDSTLQTIYRLSKGRSLTK
  AQRDTIEECLLAICNHLRPSMLQQLLRRLVFDVPQLNEYCKMPLKLLTNHYEQCWKYYCL
  PSGWGSYGLAVEEELHLTEKLFWGIFDSLSHKKYDPDLFRMALPCLSAIAGALPPDYLDT
  RITATLEKQISVDADGNFDPKPINTMNFSLPEKLEYIVTKYAEHSHDKWACDKSQSGWKY
  GISLDENVKTHPLIRPFKTLTEKEKEIYRWPARESLKTMLAVGWTVERTKEGEALVQQRE
  NEKLRSVSQANQGNSYSPAPLDLSNVVLSRELQGMVEVVAENYHNIWAKKKKLELESKGG
  GSHPLLVPYDTLTAKEKFKDREKAQDLFKFLQVNGIIVSRGMKDMELDASSMEKRFAYKF
  LKKILKYVDSAQEFIAHLEAIVSSGKTEKSPRDQEIKFFAKVLLPLVDQYFTSHCLYFLS
  SPLKPLSSSGYASHKEKEMVAGLFCKLAALVRHRISLFGSDSTTMVSCLHILAQTLDTRT
  VMKSGSELVKAGLRAFFENAAEDLEKTSENLKLGKFTHSRTQIKGVSQNINYTTVALLPI
  LTSIFEHVTQHQFGMDLLLGDVQISCYHILCSLYSLGTGKNIYVERQRPALGECLASLAA
  AIPVAFLEPTLNRYNPLSVFNTKTPRERSILGMPDTVEDMCPDIPQLEGLMKEINDLAES
  GARYTEMPHVIEVILPMLCNYLSYWWERGPENLPPSTGPCCTKVTSEHLSLILGNILKII
  NNNLGIDEASWMKRIAVYAQPIISKARPDLLRSHFIPTLEKLKKKAVKTVQEEEQLKADG
  KGDTQEAELLILDEFAVLCRDLYAFYPMLIRYVDNNRSNWLKSPDADSDQLFRMVAEVFI
  LWCKSHNFKREEQNFVIQNEINNLAFLTGDSKSKMSKAMQVKSGGQDQERKKTKRRGDLY
  SIQTSLIVAALKKMLPIGLNMCTPGDQELISLAKSRYSHRDTDEEVREHLRNNLHLQEKS
  DDPAVKWQLNLYKDVLKSEEPFNPEKTVERVQRISAAVFHLEQVEQPLRSKKAVWHKLLS
  KQRKRAVVACFRMAPLYNLPRHRSINLFLHGYQRFWIETEEYSFEEKLVQDLAKSPKVEE
  EEEEETEKQPDPLHQIILYFSRNALTERSKLEDDPLYTSYSSMMAKSCQSGEDEEEDEDK
  EKTFEEKEMEKQKTLYQQARLHERGAAEMVLQMISASKGEMSPMVVETLKLGIAILNGGN
  AGVQQKMLDYLKEKKDAGFFQSLSGLMQSCSVLDLNAFERQNKAEGLGMVTEEGTLIVRE
  RGEKVLQNDEFTRDLFRFLQLLCEGHNSDFQNFLRTQMGNTTTVNVIISTVDYLLRLQES
  ISDFYWYYSGKDIIDESGQHNFSKALAVTKQIFNSLTEYIQGPCIGNQQSLAHSRLWDAV
  VGFLHVFANMQMKLSQDSSQIELLKELLDLLQDMVVMLLSLLEGNVVNGTIGKQMVDTLV
  ESSTNVEMILKFFDMFLKLKDLTSSDTFKEYDPDGKGIISKKEFQKAMEGQKQYTQSEID
  FLLSCAEADENDMFNYVDFVDRFHEPAKDIGFNVAVLLTNLSEHMPNDSRLKCLLDPAES
  VLNYFEPYLGRIEIMGGAKKIERVYFEISESSRTQWEKPQVKESKRQFIFDVVNEGGEQE
  KMELFVNFCEDTIFEMQLASQISESDSADRPEEEEEDEDSSYVLEIAGEEEEDGSLEPAS
  AFAMACASVKRNVTDFLKRATLKNLRKQYRNVKKMTAKELVKVLFSFFWMLFVGLFQLLF
  TILGGIFQILWSTVFGGGLVEGAKNIRVTKILGDMPDPTQFGIHDDTMEAERAEVMEPGI
  TTELVHFIKGEKGDTDIMSDLFGLHPKKEGSLKHGPEVGLGDLSEIIGKDEPPTLESTVQ
  KKRKAQAAEMKAANEAEGKVESEKADMEDGEKEDKDKEEEQAEYLWTEVTKKKKRRCGQK
  VEKPEAFTANFFKGLEIYQTKLLHYLARNFYNLRFLALFVAFAINFILLFYKVTEEPLEE
  ETEDVANLWNSFNDEEEEEAMVFFVLQESTGYMAPTLRALAIIHTIISLVCVVGYYCLKV
  PLVVFKREKEIARKLEFDGLYITEQPSEDDIKGQWDRLVINTPSFPNNYWDKFVKRKVIN
  KYGDLYGAERIAELLGLDKNALDFSPVEETKAEAASLVSWLSSIDMKYHIWKLGVVFTDN
  SFLYLAWYTTMSVLGHYNNFFFAAHLLDIAMGFKTLRTILSSVTHNGKQLVLTVGLLAVV
  VYLYTVVAFNFFRKFYNKSEDDDEPDMKCDDMMTCYLFHMYVGVRAGGGIGDEIEDPAGD
  PYEMYRIVFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQVREDMETKCFICGIGNDY
  FDTTPHGFETHTLQEHNLANYLFFLMYLINKDETEHTGQESYVWKMYQERCWDFFPAGDC
  FRKQYEDQLG
• Function: Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction. May regulate Ca(2+) release by other calcium channels. Calcium channel that mediates Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum in non-muscle cells. Contributes to cellular calcium ion homeostasis. Plays a role in cellular calcium signaling.
• Tissue Specificity: Brain, skeletal muscle, placenta and possibly liver and kidney. In brain, highest levels are found in the cerebellum, hippocampus, caudate nucleus and amygdala, with lower levels in the corpus callosum, substantia nigra and thalamus.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Apelin sig.ling pathway (hsa04371)
  Circadian entrainment (hsa04713)
  Oxytocin sig.ling pathway (hsa04921)
  Salivary secretion (hsa04970)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Ion homeostasis (R-HSA-5578775)
  Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[3]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[3]
Glioma	DIS5RPEH	Strong	Genetic Variation	[5]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[1]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[6]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[3]
Myopathy	DISOWG27	Strong	Genetic Variation	[7]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[8]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[1]
Hirschsprung disease	DISUUSM1	moderate	Altered Expression	[10]
Neuromuscular disease	DISQTIJZ	moderate	Biomarker	[11]
Non-hodgkin lymphoma	DISS2Y8A	moderate	Genetic Variation	[12]
Stroke	DISX6UHX	moderate	Genetic Variation	[13]
Congenital myopathy	DISLSK9G	Disputed	Autosomal recessive	[14]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[15]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[15]
Infantile spasm	DISZSKDG	Limited	Autosomal dominant	[14]

13 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 Ryanodine receptor 3 (RYR3).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ryanodine receptor 3 (RYR3).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ryanodine receptor 3 (RYR3).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ryanodine receptor 3 (RYR3).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ryanodine receptor 3 (RYR3).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ryanodine receptor 3 (RYR3).	[21]
Marinol	DM70IK5	Approved	Marinol increases the expression of Ryanodine receptor 3 (RYR3).	[22]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Ryanodine receptor 3 (RYR3).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ryanodine receptor 3 (RYR3).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ryanodine receptor 3 (RYR3).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Ryanodine receptor 3 (RYR3).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ryanodine receptor 3 (RYR3).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ryanodine receptor 3 (RYR3).	[26]

1 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 Ryanodine receptor 3 (RYR3).	[19]

References

• [1] Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of Hypertension, Diabetes, and Alzheimer's Disease.Am J Hypertens. 2018 Jun 11;31(7):818-826. doi: 10.1093/ajh/hpy046.
• [2] Functional SNP in the microRNA-367 binding site in the 3'UTR of the calcium channel ryanodine receptor gene 3 (RYR3) affects breast cancer risk and calcification.Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13653-8. doi: 10.1073/pnas.1103360108. Epub 2011 Aug 2.
• [3] RYR3 gene polymorphisms and cardiovascular disease outcomes in the context of antihypertensive treatment.Pharmacogenomics J. 2013 Aug;13(4):330-4. doi: 10.1038/tpj.2012.22. Epub 2012 Jun 5.
• [4] Functional polymorphism in the MicroRNA-367 binding site as a prognostic factor for colonic cancer.Anticancer Res. 2013 Feb;33(2):513-9.
• [5] GOLGA7 rs11337, a Polymorphism at the MicroRNA Binding Site, Is Associated with Glioma Prognosis.Mol Ther Nucleic Acids. 2019 Dec 6;18:56-65. doi: 10.1016/j.omtn.2019.08.006. Epub 2019 Aug 14.
• [6] Deep sequencing of RYR3 gene identifies rare and common variants associated with increased carotid intima-media thickness (cIMT) in HIV-infected individuals.J Hum Genet. 2015 Feb;60(2):63-7. doi: 10.1038/jhg.2014.104. Epub 2014 Dec 11.
• [7] Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies.Eur J Neurol. 2018 Jun;25(6):841-847. doi: 10.1111/ene.13607. Epub 2018 Mar 26.
• [8] Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD.Hum Genet. 2011 Dec;130(6):795-805. doi: 10.1007/s00439-011-1033-6. Epub 2011 Jun 21.
• [9] A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium.J Med Genet. 2009 Sep;46(9):614-6. doi: 10.1136/jmg.2009.067314. Epub 2009 Jun 8.
• [10] Altered ryanodine receptor gene expression in Hirschsprung's disease.Pediatr Surg Int. 2019 Sep;35(9):923-927. doi: 10.1007/s00383-019-04504-2. Epub 2019 Jul 1.
• [11] The genomic and clinical landscape of fetal akinesia.Genet Med. 2020 Mar;22(3):511-523. doi: 10.1038/s41436-019-0680-1. Epub 2019 Nov 4.
• [12] A polymorphism at the microRNA binding site in the 3' untranslated region of C14orf101 is associated with non-Hodgkin lymphoma overall survival.Cancer Genet. 2014 Apr;207(4):141-6. doi: 10.1016/j.cancergen.2014.03.007. Epub 2014 Mar 22.
• [13] Association of the RYR3 gene polymorphisms with atherosclerosis in elderly Japanese population.BMC Cardiovasc Disord. 2014 Jan 14;14:6. doi: 10.1186/1471-2261-14-6.
• [14] 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.
• [15] RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS).Atherosclerosis. 2014 Apr;233(2):666-672. doi: 10.1016/j.atherosclerosis.2014.01.035. Epub 2014 Jan 30.
• [16] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [17] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [25] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [26] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.