Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT541Z3W)

• DOT Name: CUB and sushi domain-containing protein 2 (CSMD2)
• Synonyms: CUB and sushi multiple domains protein 2
• Gene Name: CSMD2
• Related Disease:
  Head and neck cancer
  Head and neck carcinoma
  Attention deficit hyperactivity disorder
  Colorectal carcinoma
  Depression
  Major depressive disorder
  Neoplasm
  Pancreatic cancer
  Schizophrenia
  Bipolar disorder
  Melanoma
  Acute myelogenous leukaemia
  Dementia
  Endometrial carcinoma
  Psychotic disorder
• UniProt ID: CSMD2_HUMAN
• Pfam ID: PF00431 ; PF00084
• Sequence:
  MRLISIAPGPRWQVQSHHPRSAGQNCTFQLHGPNGTVESPGFPYGYPNYANCTWTITAEE
  QHRIQLVFQSFALEEDFDVLSVFDGPPQPENLRTRLTGFQLPATIVSAATTLSLRLISDY
  AVSAQGFHATYEVLPSHTCGNPGRLPNGIQQGSTFNLGDKVRYSCNLGFFLEGHAVLTCH
  AGSENSATWDFPLPSCRADDACGGTLRGQSGIISSPHFPSEYHNNADCTWTILAELGDTI
  ALVFIDFQLEDGYDFLEVTGTEGSSLWFTGASLPAPVISSKNWLRLHFTSDGNHRQRGFS
  AQYQVKKQIELKSRGVKLMPSKDNSQKTSVLTQVGVSQGHNMCPDPGIPERGKRLGSDFR
  LGSSVQFTCNEGYDLQGSKRITCMKVSDMFAAWSDHRPVCRARMCDAHLRGPSGIITSPN
  FPIQYDNNAHCVWIITALNPSKVIKLAFEEFDLERGYDTLTVGDGGQDGDQKTVLYILTG
  TSVPDLIVSTNHQMWLLFQTDGSGSSLGFKASYEEIEQGSCGDPGIPAYGRREGSRFHHG
  DTLKFECQPAFELVGQKAITCQKNNQWSAKKPGCVFSCFFNFTSPSGVVLSPNYPEDYGN
  HLHCVWLILARPESRIHLAFNDIDVEPQFDFLVIKDGATAEAPVLGTFSGNQLPSSITSS
  GHVARLEFQTDHSTGKRGFNITFTTFRHNECPDPGVPVNGKRFGDSLQLGSSISFLCDEG
  FLGTQGSETITCVLKEGSVVWNSAVLRCEAPCGGHLTSPSGTILSPGWPGFYKDALSCAW
  VIEAQPGYPIKITFDRFKTEVNYDTLEVRDGRTYSAPLIGVYHGTQVPQFLISTSNYLYL
  LFSTDKSHSDIGFQLRYETITLQSDHCLDPGIPVNGQRHGNDFYVGALVTFSCDSGYTLS
  DGEPLECEPNFQWSRALPSCEALCGGFIQGSSGTILSPGFPDFYPNNLNCTWIIETSHGK
  GVFFTFHTFHLESGHDYLLITENGSFTQPLRQLTGSRLPAPISAGLYGNFTAQVRFISDF
  SMSYEGFNITFSEYDLEPCEEPEVPAYSIRKGLQFGVGDTLTFSCFPGYRLEGTARITCL
  GGRRRLWSSPLPRCVAECGNSVTGTQGTLLSPNFPVNYNNNHECIYSIQTQPGKGIQLKA
  RAFELSEGDVLKVYDGNNNSARLLGVFSHSEMMGVTLNSTSSSLWLDFITDAENTSKGFE
  LHFSSFELIKCEDPGTPKFGYKVHDEGHFAGSSVSFSCDPGYSLRGSEELLCLSGERRTW
  DRPLPTCVAECGGTVRGEVSGQVLSPGYPAPYEHNLNCIWTIEAEAGCTIGLHFLVFDTE
  EVHDVLRIWDGPVESGVLLKELSGPALPKDLHSTFNSVVLQFSTDFFTSKQGFAIQFSVS
  TATSCNDPGIPQNGSRSGDSWEAGDSTVFQCDPGYALQGSAEISCVKIENRFFWQPSPPT
  CIAPCGGDLTGPSGVILSPNYPEPYPPGKECDWKVTVSPDYVIALVFNIFNLEPGYDFLH
  IYDGRDSLSPLIGSFYGSQLPGRIESSSNSLFLAFRSDASVSNAGFVIDYTENPRESCFD
  PGSIKNGTRVGSDLKLGSSVTYYCHGGYEVEGTSTLSCILGPDGKPVWNNPRPVCTAPCG
  GQYVGSDGVVLSPNYPQNYTSGQICLYFVTVPKDYVVFGQFAFFHTALNDVVEVHDGHSQ
  HSRLLSSLSGSHTGESLPLATSNQVLIKFSAKGLAPARGFHFVYQAVPRTSATQCSSVPE
  PRYGKRLGSDFSVGAIVRFECNSGYALQGSPEIECLPVPGALAQWNVSAPTCVVPCGGNL
  TERRGTILSPGFPEPYLNSLNCVWKIVVPEGAGIQIQVVSFVTEQNWDSLEVFDGADNTV
  TMLGSFSGTTVPALLNSTSNQLYLHFYSDISVSAAGFHLEYKTVGLSSCPEPAVPSNGVK
  TGERYLVNDVVSFQCEPGYALQGHAHISCMPGTVRRWNYPPPLCIAQCGGTVEEMEGVIL
  SPGFPGNYPSNMDCSWKIALPVGFGAHIQFLNFSTEPNHDYIEIRNGPYETSRMMGRFSG
  SELPSSLLSTSHETTVYFHSDHSQNRPGFKLEYQDLTYSHQISSFLRGFDLSELERTNST
  PPVAASYVWDLDPGCEAYELQECPDPEPFANGIVRGAGYNVGQSVTFECLPGYQLTGHPV
  LTCQHGTNRNWDHPLPKCEVPCGGNITSSNGTVYSPGFPSPYSSSQDCVWLITVPIGHGV
  RLNLSLLQTEPSGDFITIWDGPQQTAPRLGVFTRSMAKKTVQSSSNQVLLKFHRDAATGG
  IFAIAFSAYPLTKCPPPTILPNAEVVTENEEFNIGDIVRYRCLPGFTLVGNEILTCKLGT
  YLQFEGPPPICEVHCPTNELLTDSTGVILSQSYPGSYPQFQTCSWLVRVEPDYNISLTVE
  YFLSEKQYDEFEIFDGPSGQSPLLKALSGNYSAPLIVTSSSNSVYLRWSSDHAYNRKGFK
  IRYSAPYCSLPRAPLHGFILGQTSTQPGGSIHFGCNAGYRLVGHSMAICTRHPQGYHLWS
  EAIPLCQALSCGLPEAPKNGMVFGKEYTVGTKAMYSCSEGYHLQAGAEATAECLDTGLWS
  NRNVPPQCVPVTCPDVSSISVEHGRWRLIFETQYQFQAQLMLICDPGYYYTGQRVIRCQA
  NGKWSLGDSTPTCRIISCGELPIPPNGHRIGTLSVYGATAIFSCNSGYTLVGSRVRECMA
  NGLWSGSEVRCLAGHCGTPEPIVNGHINGENYSYRGSVVYQCNAGFRLIGMSVRICQQDH
  HWSGKTPFCVLVSCGHPGSPPHSQMSGDSYTVGAVVRYSCIGKRTLVGNSTRMCGLDGHW
  TGSLPHCSGTSVGVCGDPGIPAHGIRLGDSFDPGTVMRFSCEAGHVLRGSSERTCQANGS
  WSGSQPECGVISCGNPGTPSNARVVFSDGLVFSSSIVYECREGYYATGLLSRHCSVNGTW
  TGSDPECLVINCGDPGIPANGLRLGNDFRYNKTVTYQCVPGYMMESHRVSVLSCTKDRTW
  NGTKPVCKALMCKPPPLIPNGKVVGSDFMWGSSVTYACLEGYQLSLPAVFTCEGNGSWTG
  ELPQCFPVFCGDPGVPSRGRREDRGFSYRSSVSFSCHPPLVLVGSPRRFCQSDGTWSGTQ
  PSCIDPTLTTCADPGVPQFGIQNNSQGYQVGSTVLFRCQKGYLLQGSTTRTCLPNLTWSG
  TPPDCVPHHCRQPETPTHANVGALDLPSMGYTLIYSCQEGFSLKGGSEHRTCKADGSWTG
  KPPICLEVRPSGRPINTAREPPLTQALIPGDVFAKNSLWKGAYEYQGKKQPAMLRVTGFQ
  VANSKVNATMIDHSGVELHLAGTYKKEDFHLLLQVYQITGPVEIFMNKFKDDHWALDGHV
  SSESSGATFIYQGSVKGQGFGQFGFQRLDLRLLESDPESIGRHFASNSSSVAAAILVPFI
  ALIIAGFVLYLYKHRRRPKVPFNGYAGHENTNVRATFENPMYDRNIQPTDIMASEAEFTV
  STVCTAV
• Tissue Specificity: Weakly expressed in most tissues, except in brain. Expressed at intermediate level in brain, including cerebellum, substantia nigra, hippocampus and fetal brain. Overexpressed in some head and neck cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head and neck cancer	DISBPSQZ	Definitive	Altered Expression	[1]
Head and neck carcinoma	DISOU1DS	Definitive	Altered Expression	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	Posttranslational Modification	[6]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[7]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[8]
Melanoma	DIS1RRCY	moderate	Biomarker	[9]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[10]
Dementia	DISXL1WY	Limited	Genetic Variation	[7]
Endometrial carcinoma	DISXR5CY	Limited	Genetic Variation	[11]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[7]

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 CUB and sushi domain-containing protein 2 (CSMD2).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of CUB and sushi domain-containing protein 2 (CSMD2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of CUB and sushi domain-containing protein 2 (CSMD2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[16]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CUB and sushi domain-containing protein 2 (CSMD2).	[20]

References

• [1] Identification of two new members of the CSMD gene family.Genomics. 2003 Sep;82(3):412-5. doi: 10.1016/s0888-7543(03)00149-6.
• [2] Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.J Neural Transm (Vienna). 2008 Nov;115(11):1573-85. doi: 10.1007/s00702-008-0119-3. Epub 2008 Oct 7.
• [3] Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients.Tumour Biol. 2014 May;35(5):4419-23. doi: 10.1007/s13277-013-1581-6. Epub 2014 Jan 10.
• [4] Genome-wide association study of comorbid depressive syndrome and alcohol dependence.Psychiatr Genet. 2012 Feb;22(1):31-41. doi: 10.1097/YPG.0b013e32834acd07.
• [5] The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response.Transl Psychiatry. 2015 Apr 21;5(4):e553. doi: 10.1038/tp.2015.47.
• [6] Identification of epigenetically silenced genes in human pancreatic cancer by a novel method "microarray coupled with methyl-CpG targeted transcriptional activation" (MeTA-array). Biochem Biophys Res Commun. 2011 Jul 22;411(1):162-7.
• [7] A genetic association study of CSMD1 and CSMD2 with cognitive function.Brain Behav Immun. 2017 Mar;61:209-216. doi: 10.1016/j.bbi.2016.11.026. Epub 2016 Nov 25.
• [8] Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.Lancet. 2016 Mar 12;387(10023):1085-1093. doi: 10.1016/S0140-6736(16)00143-4. Epub 2016 Jan 22.
• [9] Genome-wide characterization of circulating tumor cells identifies novel prognostic genomic alterations in systemic melanoma metastasis.Clin Chem. 2014 Jun;60(6):873-85. doi: 10.1373/clinchem.2013.213611. Epub 2014 Apr 9.
• [10] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [11] Identification of nine new susceptibility loci for endometrial cancer.Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7.
• [12] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [13] 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.
• [14] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [15] 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.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] 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.
• [20] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.