Details of Drug Off-Target (DOT)

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

• DOT Name: SET-binding protein (SETBP1)
• Synonyms: SEB
• Gene Name: SETBP1
• Related Disease:
  Autism
  Childhood myelodysplastic syndrome
  Complex neurodevelopmental disorder
  Hepatitis
  Hepatitis A virus infection
  Neurodevelopmental disorder
  Schinzel-Giedion syndrome
  Acute myelogenous leukaemia
  Androgen insensitivity syndrome
  Arthrogryposis
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chromosomal disorder
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Fanconi anemia complementation group A
  Fanconi's anemia
  Gastric cancer
  Gastric neoplasm
  Intellectual disability, autosomal dominant 29
  Myelodysplastic syndrome
  Neoplasm
  Refractory chronic myeloid leukaemia
  Stomach cancer
  Toxic shock syndrome
  Trichohepatoenteric syndrome
  Triple negative breast cancer
  Intellectual disability
  leukaemia
  Myeloid leukaemia
  Primary myelofibrosis
  Obsolete intellectual disability-expressive aphasia-facial dysmorphism syndrome
  Advanced cancer
  Alopecia
  Asthma
  Leukemia
  Myeloproliferative neoplasm
  Plasma cell myeloma
  T-cell acute lymphoblastic leukaemia
• UniProt ID: SETBP_HUMAN
• Sequence:
  MESRETLSSSRQRGGESDFLPVSSAKPPAAPGCAGEPLLSTPGPGKGIPVGGERMEPEEE
  DELGSGRDVDSNSNADSEKWVAGDGLEEQEFSIKEANFTEGSLKLKIQTTKRAKKPPKNL
  ENYICPPEIKITIKQSGDQKVSRAGKNSKATKEEERSHSKKKLLTASDLAASDLKGFQPQ
  AYERPQKHSTLHYDTGLPQDFTGDTLKPKHQQKSSSQNHMDWSTNSDSGPVTQNCFISPE
  SGRETASTSKIPALEPVASFAKAQGKKGSAGNTWSQLSNNNKDLLLGGVAPSPSSHSSPA
  PPSSSAECNGLQPLVDQDGGGTKEPPEPPTVGSKKKSSKKDVISQTIPNPDLDWVKNAQK
  AFDNTEGKREGYSADSAQEASPARQNVSSASNPENDSSHVRITIPIKAPSLDPTNHKRKK
  RQSIKAVVEKIMPEKALASGITMSSEVVNRILSNSEGNKKDPRVPKLSKMIENESPSVGL
  ETGGNAEKVIPGGVSKPRKPPMVMTPPTCTDHSPSRKLPEIQHPKFAAKRRWTCSKPKPS
  TMLREAVMATSDKLMLEPPSAYPITPSSPLYTNTDSLTVITPVKKKRGRPKKQPLLTVET
  IHEGTSTSPVSPISREFPGTKKRKRRRNLAKLAQLVPGEDKPMSEMKFHKKVGKLGVLDK
  KTIKTINKMKTLKRKNILNQILSCSSSVALKAKAPPETSPGAAAIESKLGKQINVSKRGT
  IYIGKKRGRKPRAELPPPSEEPKTAIKHPRPVSSQPDVPAVPSNFQSLVASSPAAMHPLS
  TQLGGSNGNLSPASTETNFSELKTMPNLQPISALPTKTQKGIHSGTWKLSPPRLMANSPS
  HLCEIGSLKEITLSPVSESHSEETIPSDSGIGTDNNSTSDQAEKSSESRRRYSFDFCSLD
  NPEAIPSDTSTKNRHGHRQKHLIVDNFLAHESLKKPKHKRKRKSLQNRDDLQFLADLEEL
  ITKFQVFRISHRSYTFYHENPYPSIFRINFDHYYPVPYIQYDPLLYLRRTSDLKSKKKRG
  RPAKTNDTMTKVPFLQGFSYPIPSGSYYAPYGMPYTSMPMMNLGYYGQYPAPLYLSHTLG
  AASPFMRPTVPPPQFHTNSHVKMSGAAKHKAKHGVHLQGPVSMGLGDMQPSLNPPKVGSA
  SLSSGRLHKRKHKHKHKHKEDRILGTHDNLSGLFAGKATGFSSHILSERLSSADKELPLV
  SEKNKHKEKQKHQHSEAGHKASKNNFEVDTLSTLSLSDAQHWTQAKEKGDLSSEPVDSCT
  KRYSGSGGDGGSTRSENLDVFSEMNPSNDKWDSDVSGSKRRSYEGFGTYREKDIQAFKMN
  RKERSSYDSSMSPGMPSPHLKVDQTAVHSKNEGSVPTMMTRKKPAAVDSVTIPPAPVLSL
  LAASAATSDAVGSSLKKRFKRREIEAIQCEVRKMCNYTKILSTKKNLDHVNKILKAKRLQ
  RQSKTGNNFVKKRRGRPRKQPTQFDEDSRDQMPVLEKCIDLPSKRGQKPSLSPLVLEPAA
  SQDTIMATIEAVIHMAREAPPLPPPPPPPLPPPPPPPLPPPPPLPKTPRGGKRKHKPQAP
  AQPPQQSPPQQPLPQEEEVKAKRQRKSRGSESEVLP
• Tissue Specificity: Expressed in numerous tissues. Expressed at low levels in myeloid and monocytic cells as well as in CD34+ cells; expression levels are higher in myeloid malignancies.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Childhood myelodysplastic syndrome	DISMN80I	Definitive	Genetic Variation	[2]
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[3]
Hepatitis	DISXXX35	Definitive	Biomarker	[4]
Hepatitis A virus infection	DISUMFQV	Definitive	Biomarker	[4]
Neurodevelopmental disorder	DIS372XH	Definitive	Biomarker	[5]
Schinzel-Giedion syndrome	DISSBXAV	Definitive	Autosomal dominant	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Androgen insensitivity syndrome	DISUZBBO	Strong	Biomarker	[6]
Arthrogryposis	DISC81CM	Strong	CausalMutation	[7]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[11]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[12]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Biomarker	[14]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[15]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Genetic Variation	[16]
Fanconi's anemia	DISGW6Q8	Strong	Genetic Variation	[16]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[17]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[17]
Intellectual disability, autosomal dominant 29	DIS3TFC6	Strong	Autosomal dominant	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[19]
Refractory chronic myeloid leukaemia	DIS40YPP	Strong	Genetic Variation	[20]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[17]
Toxic shock syndrome	DISX5S53	Strong	Biomarker	[21]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Intellectual disability	DISMBNXP	moderate	Biomarker	[1]
leukaemia	DISS7D1V	moderate	Genetic Variation	[24]
Myeloid leukaemia	DISMN944	moderate	Biomarker	[25]
Primary myelofibrosis	DIS6L0CN	moderate	Genetic Variation	[11]
Obsolete intellectual disability-expressive aphasia-facial dysmorphism syndrome	DISC0WSY	Supportive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[14]
Alopecia	DIS37HU4	Limited	Genetic Variation	[26]
Asthma	DISW9QNS	Limited	Genetic Variation	[27]
Leukemia	DISNAKFL	Limited	Altered Expression	[28]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[29]
Plasma cell myeloma	DIS0DFZ0	Limited	Genetic Variation	[30]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Genetic Variation	[31]

2 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 SET-binding protein (SETBP1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SET-binding protein (SETBP1).	[43]

14 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 SET-binding protein (SETBP1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SET-binding protein (SETBP1).	[34]
Marinol	DM70IK5	Approved	Marinol increases the expression of SET-binding protein (SETBP1).	[35]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of SET-binding protein (SETBP1).	[36]
Selenium	DM25CGV	Approved	Selenium decreases the expression of SET-binding protein (SETBP1).	[37]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of SET-binding protein (SETBP1).	[38]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of SET-binding protein (SETBP1).	[39]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of SET-binding protein (SETBP1).	[40]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of SET-binding protein (SETBP1).	[41]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of SET-binding protein (SETBP1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of SET-binding protein (SETBP1).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SET-binding protein (SETBP1).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SET-binding protein (SETBP1).	[45]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of SET-binding protein (SETBP1).	[46]

References

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• [3] 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.
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• [33] 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.
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