Details of Drug Off-Target (DOT)

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

• DOT Name: Protein turtle homolog B (IGSF9B)
• Synonyms: Immunoglobulin superfamily member 9B; IgSF9B
• Gene Name: IGSF9B
• Related Disease:
  Multiple sclerosis
  Schizophrenia
  Alcohol dependence
  Alcohol-induced disorders
  Alcohol-related disorders
  Bipolar disorder
  Major depressive disorder
  Anxiety
  Anxiety disorder
  Mood disorder
• UniProt ID: TUTLB_HUMAN
• Pfam ID: PF00041 ; PF13895 ; PF13927
• Sequence:
  MIWYVATFIASVIGTRGLAAEGAHGLREEPEFVTARAGESVVLRCDVIHPVTGQPPPYVV
  EWFKFGVPIPIFIKFGYYPPHVDPEYAGRASLHDKASLRLEQVRSEDQGWYECKVLMLDQ
  QYDTFHNGSWVHLTINAPPTFTETPPQYIEAKEGGSITMTCTAFGNPKPIVTWLKEGTLL
  GASGKYQVSDGSLTVTSVSREDRGAYTCRAYSIQGEAVHTTHLLVQGPPFIVSPPENITV
  NISQDALLTCRAEAYPGNLTYTWYWQDENVYFQNDLKLRVRILIDGTLIIFRVKPEDSGK
  YTCVPSNSLGRSPSASAYLTVQYPARVLNMPPVIYVPVGIHGYIRCPVDAEPPATVVKWN
  KDGRPLQVEKNLGWTLMEDGSIRIEEATEEALGTYTCVPYNTLGTMGQSAPARLVLKDPP
  YFTVLPGWEYRQEAGRELLIPCAAAGDPFPVITWRKVGKPSRSKHSALPSGSLQFRALSK
  EDHGEWECVATNVVTSITASTHLTVIGTSPHAPGSVRVQVSMTTANVSWEPGYDGGYEQT
  FSVWMKRAQFGPHDWLSLPVPPGPSWLLVDTLEPETAYQFSVLAQNKLGTSAFSEVVTVN
  TLAFPITTPEPLVLVTPPRCLIANRTQQGVLLSWLPPANHSFPIDRYIMEFRVAERWELL
  DDGIPGTEGEFFAKDLSQDTWYEFRVLAVMQDLISEPSNIAGVSSTDIFPQPDLTEDGLA
  RPVLAGIVATICFLAAAILFSTLAACFVNKQRKRKLKRKKDPPLSITHCRKSLESPLSSG
  KVSPESIRTLRAPSESSDDQGQPAAKRMLSPTREKELSLYKKTKRAISSKKYSVAKAEAE
  AEATTPIELISRGPDGRFVMDPAEMEPSLKSRRIEGFPFAEETDMYPEFRQSDEENEDPL
  VPTSVAALKSQLTPLSSSQESYLPPPAYSPRFQPRGLEGPGGLEGRLQATGQARPPAPRP
  FHHGQYYGYLSSSSPGEVEPPPFYVPEVGSPLSSVMSSPPLPTEGPFGHPTIPEENGENA
  SNSTLPLTQTPTGGRSPEPWGRPEFPFGGLETPAMMFPHQLPPCDVPESLQPKAGLPRGL
  PPTSLQVPAAYPGILSLEAPKGWAGKSPGRGPVPAPPAAKWQDRPMQPLVSQGQLRHTSQ
  GMGIPVLPYPEPAEPGAHGGPSTFGLDTRWYEPQPRPRPSPRQARRAEPSLHQVVLQPSR
  LSPLTQSPLSSRTGSPELAARARPRPGLLQQAEMSEITLQPPAAVSFSRKSTPSTGSPSQ
  SSRSGSPSYRPAMGFTTLATGYPSPPPGPAPAGPGDSLDVFGQTPSPRRTGEELLRPETP
  PPTLPTSGKLQRDRPAPATSPPERALSKL
• Function: Transmembrane protein which is abundantly expressed in interneurons, where it may regulate inhibitory synapse development. May mediate homophilic cell adhesion.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[3]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[3]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[3]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[4]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[3]
Anxiety	DISIJDBA	Limited	Biomarker	[5]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[5]
Mood disorder	DISLVMWO	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein turtle homolog B (IGSF9B).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein turtle homolog B (IGSF9B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein turtle homolog B (IGSF9B).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein turtle homolog B (IGSF9B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein turtle homolog B (IGSF9B).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein turtle homolog B (IGSF9B).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein turtle homolog B (IGSF9B).	[11]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of Protein turtle homolog B (IGSF9B).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein turtle homolog B (IGSF9B).	[14]

References

• [1] Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course.J Neuroinflammation. 2018 Sep 14;15(1):265. doi: 10.1186/s12974-018-1307-1.
• [2] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [3] Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression.JAMA Psychiatry. 2017 Dec 1;74(12):1234-1241. doi: 10.1001/jamapsychiatry.2017.3275.
• [4] A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.Mol Psychiatry. 2018 Mar;23(3):639-647. doi: 10.1038/mp.2016.259. Epub 2017 Jan 24.
• [5] IgSF9b regulates anxiety behaviors through effects on centromedial amygdala inhibitory synapses.Nat Commun. 2018 Dec 20;9(1):5400. doi: 10.1038/s41467-018-07762-1.
• [6] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] 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.
• [12] Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211065972. doi: 10.1177/09603271211065972.
• [13] 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.
• [14] 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.