Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIVDSC4)

• DOT Name: CUB and sushi domain-containing protein 1 (CSMD1)
• Synonyms: CUB and sushi multiple domains protein 1
• Gene Name: CSMD1
• Related Disease:
  Gastric cancer
  Intervertebral disc degeneration
  Multiple sclerosis
  Stomach cancer
  Advanced cancer
  Alzheimer disease
  Attention deficit hyperactivity disorder
  Breast cancer
  Breast neoplasm
  Carcinoma
  Chronic bronchitis
  Colorectal neoplasm
  Drug dependence
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  High blood pressure
  Juvenile idiopathic arthritis
  Major depressive disorder
  Malaria
  Mental disorder
  Neoplasm
  Palmoplantar pustulosis
  Prostate cancer
  Prostate neoplasm
  Psoriasis
  Squamous cell carcinoma
  Substance abuse
  Substance dependence
  Urinary bladder neoplasm
  Uterine fibroids
  Acute myelogenous leukaemia
  Asthma
  Bipolar disorder
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Liver cancer
  Schizoaffective disorder
  Skin cancer
  Adenocarcinoma
  Parkinson disease
  Autism spectrum disorder
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Dementia
  Hepatocellular carcinoma
• UniProt ID: CSMD1_HUMAN
• PDB ID: 2EHF
• Pfam ID: PF00431 ; PF00084
• Sequence:
  MTAWRRFQSLLLLLGLLVLCARLLTAAKGQNCGGLVQGPNGTIESPGFPHGYPNYANCTW
  IIITGERNRIQLSFHTFALEEDFDILSVYDGQPQQGNLKVRLSGFQLPSSIVSTGSILTL
  WFTTDFAVSAQGFKALYEVLPSHTCGNPGEILKGVLHGTRFNIGDKIRYSCLPGYILEGH
  AILTCIVSPGNGASWDFPAPFCRAEGACGGTLRGTSSSISSPHFPSEYENNADCTWTILA
  EPGDTIALVFTDFQLEEGYDFLEISGTEAPSIWLTGMNLPSPVISSKNWLRLHFTSDSNH
  RRKGFNAQFQVKKAIELKSRGVKMLPSKDGSHKNSVLSQGGVALVSDMCPDPGIPENGRR
  AGSDFRVGANVQFSCEDNYVLQGSKSITCQRVTETLAAWSDHRPICRARTCGSNLRGPSG
  VITSPNYPVQYEDNAHCVWVITTTDPDKVIKLAFEEFELERGYDTLTVGDAGKVGDTRSV
  LYVLTGSSVPDLIVSMSNQMWLHLQSDDSIGSPGFKAVYQEIEKGGCGDPGIPAYGKRTG
  SSFLHGDTLTFECPAAFELVGERVITCQQNNQWSGNKPSCVFSCFFNFTASSGIILSPNY
  PEEYGNNMNCVWLIISEPGSRIHLIFNDFDVEPQFDFLAVKDDGISDITVLGTFSGNEVP
  SQLASSGHIVRLEFQSDHSTTGRGFNITYTTFGQNECHDPGIPINGRRFGDRFLLGSSVS
  FHCDDGFVKTQGSESITCILQDGNVVWSSTVPRCEAPCGGHLTASSGVILPPGWPGYYKD
  SLHCEWIIEAKPGHSIKITFDRFQTEVNYDTLEVRDGPASSSPLIGEYHGTQAPQFLIST
  GNFMYLLFTTDNSRSSIGFLIHYESVTLESDSCLDPGIPVNGHRHGGDFGIRSTVTFSCD
  PGYTLSDDEPLVCERNHQWNHALPSCDALCGGYIQGKSGTVLSPGFPDFYPNSLNCTWTI
  EVSHGKGVQMIFHTFHLESSHDYLLITEDGSFSEPVARLTGSVLPHTIKAGLFGNFTAQL
  RFISDFSISYEGFNITFSEYDLEPCDDPGVPAFSRRIGFHFGVGDSLTFSCFLGYRLEGA
  TKLTCLGGGRRVWSAPLPRCVAECGASVKGNEGTLLSPNFPSNYDNNHECIYKIETEAGK
  GIHLRTRSFQLFEGDTLKVYDGKDSSSRPLGTFTKNELLGLILNSTSNHLWLEFNTNGSD
  TDQGFQLTYTSFDLVKCEDPGIPNYGYRIRDEGHFTDTVVLYSCNPGYAMHGSNTLTCLS
  GDRRVWDKPLPSCIAECGGQIHAATSGRILSPGYPAPYDNNLHCTWIIEADPGKTISLHF
  IVFDTEMAHDILKVWDGPVDSDILLKEWSGSALPEDIHSTFNSLTLQFDSDFFISKSGFS
  IQFSTSIAATCNDPGMPQNGTRYGDSREAGDTVTFQCDPGYQLQGQAKITCVQLNNRFFW
  QPDPPTCIAACGGNLTGPAGVILSPNYPQPYPPGKECDWRVKVNPDFVIALIFKSFNMEP
  SYDFLHIYEGEDSNSPLIGSYQGSQAPERIESSGNSLFLAFRSDASVGLSGFAIEFKEKP
  REACFDPGNIMNGTRVGTDFKLGSTITYQCDSGYKILDPSSITCVIGADGKPSWDQVLPS
  CNAPCGGQYTGSEGVVLSPNYPHNYTAGQICLYSITVPKEFVVFGQFAYFQTALNDLAEL
  FDGTHAQARLLSSLSGSHSGETLPLATSNQILLRFSAKSGASARGFHFVYQAVPRTSDTQ
  CSSVPEPRYGRRIGSEFSAGSIVRFECNPGYLLQGSTALHCQSVPNALAQWNDTIPSCVV
  PCSGNFTQRRGTILSPGYPEPYGNNLNCIWKIIVTEGSGIQIQVISFATEQNWDSLEIHD
  GGDVTAPRLGSFSGTTVPALLNSTSNQLYLHFQSDISVAAAGFHLEYKTVGLAACQEPAL
  PSNSIKIGDRYMVNDVLSFQCEPGYTLQGRSHISCMPGTVRRWNYPSPLCIATCGGTLST
  LGGVILSPGFPGSYPNNLDCTWRISLPIGYGAHIQFLNFSTEANHDFLEIQNGPYHTSPM
  IGQFSGTDLPAALLSTTHETLIHFYSDHSQNRQGFKLAYQAYELQNCPDPPPFQNGYMIN
  SDYSVGQSVSFECYPGYILIGHPVLTCQHGINRNWNYPFPRCDAPCGYNVTSQNGTIYSP
  GFPDEYPILKDCIWLITVPPGHGVYINFTLLQTEAVNDYIAVWDGPDQNSPQLGVFSGNT
  ALETAYSSTNQVLLKFHSDFSNGGFFVLNFHAFQLKKCQPPPAVPQAEMLTEDDDFEIGD
  FVKYQCHPGYTLVGTDILTCKLSSQLQFEGSLPTCEAQCPANEVRTGSSGVILSPGYPGN
  YFNSQTCSWSIKVEPNYNITIFVDTFQSEKQFDALEVFDGSSGQSPLLVVLSGNHTEQSN
  FTSRSNQLYLRWSTDHATSKKGFKIRYAAPYCSLTHPLKNGGILNRTAGAVGSKVHYFCK
  PGYRMVGHSNATCRRNPLGMYQWDSLTPLCQAVSCGIPESPGNGSFTGNEFTLDSKVVYE
  CHEGFKLESSQQATAVCQEDGLWSNKGKPPTCKPVACPSIEAQLSEHVIWRLVSGSLNEY
  GAQVLLSCSPGYYLEGWRLLRCQANGTWNIGDERPSCRVISCGSLSFPPNGNKIGTLTVY
  GATAIFTCNTGYTLVGSHVRECLANGLWSGSETRCLAGHCGSPDPIVNGHISGDGFSYRD
  TVVYQCNPGFRLVGTSVRICLQDHKWSGQTPVCVPITCGHPGNPAHGFTNGSEFNLNDVV
  NFTCNTGYLLQGVSRAQCRSNGQWSSPLPTCRVVNCSDPGFVENAIRHGQQNFPESFEYG
  MSILYHCKKGFYLLGSSALTCMANGLWDRSLPKCLAISCGHPGVPANAVLTGELFTYGAV
  VHYSCRGSESLIGNDTRVCQEDSHWSGALPHCTGNNPGFCGDPGTPAHGSRLGDDFKTKS
  LLRFSCEMGHQLRGSPERTCLLNGSWSGLQPVCEAVSCGNPGTPTNGMIVSSDGILFSSS
  VIYACWEGYKTSGLMTRHCTANGTWTGTAPDCTIISCGDPGTLANGIQFGTDFTFNKTVS
  YQCNPGYVMEAVTSATIRCTKDGRWNPSKPVCKAVLCPQPPPVQNGTVEGSDFRWGSSIS
  YSCMDGYQLSHSAILSCEGRGVWKGEIPQCLPVFCGDPGIPAEGRLSGKSFTYKSEVFFQ
  CKSPFILVGSSRRVCQADGTWSGIQPTCIDPAHNTCPDPGTPHFGIQNSSRGYEVGSTVF
  FRCRKGYHIQGSTTRTCLANLTWSGIQTECIPHACRQPETPAHADVRAIDLPTFGYTLVY
  TCHPGFFLAGGSEHRTCKADMKWTGKSPVCKSKGVREVNETVTKTPVPSDVFFVNSLWKG
  YYEYLGKRQPATLTVDWFNATSSKVNATFSEASPVELKLTGIYKKEEAHLLLKAFQIKGQ
  ADIFVSKFENDNWGLDGYVSSGLERGGFTFQGDIHGKDFGKFKLERQDPLNPDQDSSSHY
  HGTSSGSVAAAILVPFFALILSGFAFYLYKHRTRPKVQYNGYAGHENSNGQASFENPMYD
  TNLKPTEAKAVRFDTTLNTVCTVV
• Function: Potential suppressor of squamous cell carcinomas.
• Tissue Specificity: Weakly expressed in most tissues, except in brain. Expressed at intermediate level in brain, including cerebellum, substantia nigra, hippocampus and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Intervertebral disc degeneration	DISG3AIM	Definitive	Genetic Variation	[2]
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[3]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[5]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Chronic bronchitis	DISS8O8V	Strong	Genetic Variation	[9]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[10]
Drug dependence	DIS9IXRC	Strong	Biomarker	[11]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[12]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Biomarker	[13]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[14]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[6]
Malaria	DISQ9Y50	Strong	Genetic Variation	[15]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[18]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[19]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[20]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[22]
Substance abuse	DIS327VW	Strong	Biomarker	[11]
Substance dependence	DISDRAAR	Strong	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[23]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[24]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[25]
Asthma	DISW9QNS	moderate	Genetic Variation	[26]
Bipolar disorder	DISAM7J2	moderate	Biomarker	[27]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[28]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[29]
Liver cancer	DISDE4BI	moderate	Biomarker	[28]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[30]
Skin cancer	DISTM18U	moderate	Biomarker	[22]
Adenocarcinoma	DIS3IHTY	Disputed	Genetic Variation	[31]
Parkinson disease	DISQVHKL	Disputed	Genetic Variation	[32]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[33]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[4]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[26]
Dementia	DISXL1WY	Limited	Genetic Variation	[34]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[35]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	CUB and sushi domain-containing protein 1 (CSMD1) affects the response to substance of Methamphetamine.	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of CUB and sushi domain-containing protein 1 (CSMD1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of CUB and sushi domain-containing protein 1 (CSMD1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of CUB and sushi domain-containing protein 1 (CSMD1).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of CUB and sushi domain-containing protein 1 (CSMD1).	[38]

References

• [1] Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-B pathway.Int J Biol Sci. 2019 Aug 6;15(10):2075-2086. doi: 10.7150/ijbs.23802. eCollection 2019.
• [2] Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.Ann Rheum Dis. 2013 Jul;72(7):1141-8. doi: 10.1136/annrheumdis-2012-201551. Epub 2012 Sep 19.
• [3] Replication of top markers of a genome-wide association study in multiple sclerosis in Spain.Genes Immun. 2011 Mar;12(2):110-5. doi: 10.1038/gene.2010.52. Epub 2010 Oct 14.
• [4] Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion.Oncol Rep. 2017 Jul;38(1):283-292. doi: 10.3892/or.2017.5656. Epub 2017 May 22.
• [5] Genetic data and cognitively defined late-onset Alzheimer's disease subgroups.Mol Psychiatry. 2020 Nov;25(11):2942-2951. doi: 10.1038/s41380-018-0298-8. Epub 2018 Dec 4.
• [6] Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.
• [7] Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer.Oncotarget. 2016 Nov 22;7(47):76920-76933. doi: 10.18632/oncotarget.12729.
• [8] Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas.Cancer Res. 2009 May 1;69(9):4036-42. doi: 10.1158/0008-5472.CAN-08-3913. Epub 2009 Apr 21.
• [9] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
• [10] Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1) gene reveals association with early age of diagnosis in colorectal cancer patients.PLoS One. 2013;8(3):e58731. doi: 10.1371/journal.pone.0058731. Epub 2013 Mar 7.
• [11] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [12] Clinical Significance of CUB and Sushi Multiple Domains 1 Inactivation in Head and Neck Squamous Cell Carcinoma.Int J Mol Sci. 2018 Dec 12;19(12):3996. doi: 10.3390/ijms19123996.
• [13] TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.J Hypertens. 2015 Jun;33(6):1301-9. doi: 10.1097/HJH.0000000000000541.
• [14] Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.Pharmacogenomics J. 2014 Aug;14(4):356-64. doi: 10.1038/tpj.2014.3. Epub 2014 Apr 8.
• [15] Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.PLoS Genet. 2018 Jan 30;14(1):e1007172. doi: 10.1371/journal.pgen.1007172. eCollection 2018 Jan.
• [16] Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.Mol Psychiatry. 2014 Feb;19(2):228-34. doi: 10.1038/mp.2012.183. Epub 2013 Jan 15.
• [17] Clinical significance of YAP1 activation in head and neck squamous cell carcinoma.Oncotarget. 2017 Nov 27;8(67):111130-111143. doi: 10.18632/oncotarget.22666. eCollection 2017 Dec 19.
• [18] Association analyses identify six new psoriasis susceptibility loci in the Chinese population.Nat Genet. 2010 Nov;42(11):1005-9. doi: 10.1038/ng.690. Epub 2010 Oct 17.
• [19] A genome-wide association study of prostate cancer in West African men.Hum Genet. 2014 May;133(5):509-21. doi: 10.1007/s00439-013-1387-z. Epub 2013 Nov 2.
• [20] Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse.Cancer Res. 2003 Jul 15;63(14):4196-203.
• [21] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [22] Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues.Cancer Biol Ther. 2009 May;8(10):907-16. doi: 10.4161/cbt.8.10.8132. Epub 2009 May 9.
• [23] Bladder cancer stage and outcome by array-based comparative genomic hybridization.Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):7012-22. doi: 10.1158/1078-0432.CCR-05-0177.
• [24] A multi-stage genome-wide association study of uterine fibroids in African Americans.Hum Genet. 2017 Oct;136(10):1363-1373. doi: 10.1007/s00439-017-1836-1. Epub 2017 Aug 23.
• [25] 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.
• [26] The clinical and genetic features of COPD-asthma overlap syndrome.Eur Respir J. 2014 Aug;44(2):341-50. doi: 10.1183/09031936.00216013. Epub 2014 May 29.
• [27] Genome-Wide Association Study of Psychosis Proneness in the Finnish Population.Schizophr Bull. 2017 Oct 21;43(6):1304-1314. doi: 10.1093/schbul/sbx006.
• [28] Allelic imbalances and homozygous deletion on 8p23.2 for stepwise progression of hepatocarcinogenesis.Hepatology. 2009 Feb;49(2):513-22. doi: 10.1002/hep.22698.
• [29] Copy number variation analysis and targeted NGS in 77 families with suspected Lynch syndrome reveals novel potential causative genes.Int J Cancer. 2018 Dec 1;143(11):2800-2813. doi: 10.1002/ijc.31725. Epub 2018 Oct 3.
• [30] GWAS meta analysis identifies TSNARE1 as a novel Schizophrenia / Bipolar susceptibility locus.Sci Rep. 2013 Oct 29;3:3075. doi: 10.1038/srep03075.
• [31] Somatic mutations to CSMD1 in colorectal adenocarcinomas.Cancer Biol Ther. 2008 Apr;7(4):609-13. doi: 10.4161/cbt.7.4.5623.
• [32] The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson's disease in Iranian population.Neurol Sci. 2016 May;37(5):731-6. doi: 10.1007/s10072-015-2420-x. Epub 2016 Jan 5.
• [33] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [34] 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.
• [35] Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.PeerJ. 2019 Feb 6;7:e6375. doi: 10.7717/peerj.6375. eCollection 2019.
• [36] 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.
• [37] 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.
• [38] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [39] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.