Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT30DED5)

• DOT Name: Protein CBFA2T1 (RUNX1T1)
• Synonyms: Cyclin-D-related protein; Eight twenty one protein; Protein ETO; Protein MTG8; Zinc finger MYND domain-containing protein 2
• Gene Name: RUNX1T1
• Related Disease:
  B-cell neoplasm
  Childhood acute lymphoblastic leukemia
  Myeloid leukaemia
  Promyelocytic leukaemia
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute myelomonocytic leukemia M4
  Acute respiratory failure
  Advanced cancer
  Amyloidosis
  Anemia
  Cerebellar degeneration
  Childhood kidney Wilms tumor
  Chromosomal disorder
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Dementia
  Depression
  Epithelial ovarian cancer
  Glaucoma/ocular hypertension
  Influenza
  Lupus
  Metastatic malignant neoplasm
  Myeloproliferative neoplasm
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Rheumatic fever
  Systemic lupus erythematosus
  Systemic mastocytosis
  Wilms tumor
  Breast cancer
  Breast carcinoma
  High blood pressure
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Myelodysplastic syndrome
  Acute monocytic leukemia
  Bacterial infection
  Cognitive impairment
  Intellectual disability
  Neoplasm
• UniProt ID: MTG8_HUMAN
• PDB ID: 1WQ6; 2DJ8; 2H7B; 2KNH; 2KYG; 2OD1; 2ODD; 2PP4; 4JOL
• Pfam ID: PF08788 ; PF07531 ; PF01753
• Sequence:
  MISVKRNTWRALSLVIGDCRKKGNFEYCQDRTEKHSTMPDSPVDVKTQSRLTPPTMPPPP
  TTQGAPRTSSFTPTTLTNGTSHSPTALNGAPSPPNGFSNGPSSSSSSSLANQQLPPACGA
  RQLSKLKRFLTTLQQFGNDISPEIGERVRTLVLGLVNSTLTIEEFHSKLQEATNFPLRPF
  VIPFLKANLPLLQRELLHCARLAKQNPAQYLAQHEQLLLDASTTSPVDSSELLLDVNENG
  KRRTPDRTKENGFDREPLHSEHPSKRPCTISPGQRYSPNNGLSYQPNGLPHPTPPPPQHY
  RLDDMAIAHHYRDSYRHPSHRDLRDRNRPMGLHGTRQEEMIDHRLTDREWAEEWKHLDHL
  LNCIMDMVEKTRRSLTVLRRCQEADREELNYWIRRYSDAEDLKKGGGSSSSHSRQQSPVN
  PDPVALDAHREFLHRPASGYVPEEIWKKAEEAVNEVKRQAMTELQKAVSEAERKAHDMIT
  TERAKMERTVAEAKRQAAEDALAVINQQEDSSESCWNCGRKASETCSGCNTARYCGSFCQ
  HKDWEKHHHICGQTLQAQQQGDTPAVSSSVTPNSGAGSPMDTPPAATPRSTTPGTPSTIE
  TTPR
• Function: Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Can repress the expression of MMP7 in a ZBTB33-dependent manner. Can repress transactivation mediated by TCF12. Acts as a negative regulator of adipogenesis. The AML1-MTG8/ETO fusion protein frequently found in leukemic cells is involved in leukemogenesis and contributes to hematopoietic stem/progenitor cell self-renewal.
• Tissue Specificity: Most abundantly expressed in brain. Lower levels in lung, heart, testis and ovary.
• KEGG Pathway:
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Genetic Variation	[2]
Myeloid leukaemia	DISMN944	Definitive	Genetic Variation	[3]
Promyelocytic leukaemia	DISYGG13	Definitive	Genetic Variation	[4]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[5]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[6]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[7]
Acute respiratory failure	DIS5KQ5Y	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Amyloidosis	DISHTAI2	Strong	Biomarker	[10]
Anemia	DISTVL0C	Strong	Genetic Variation	[11]
Cerebellar degeneration	DISPBCM3	Strong	Genetic Variation	[12]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[13]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[14]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[15]
Colon cancer	DISVC52G	Strong	Biomarker	[16]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[16]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[17]
Dementia	DISXL1WY	Strong	Biomarker	[18]
Depression	DIS3XJ69	Strong	Biomarker	[19]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[20]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Altered Expression	[21]
Influenza	DIS3PNU3	Strong	Genetic Variation	[22]
Lupus	DISOKJWA	Strong	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[24]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Altered Expression	[25]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[26]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[20]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[20]
Rheumatic fever	DISLUF66	Strong	Biomarker	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[23]
Systemic mastocytosis	DISNQ2OY	Strong	Genetic Variation	[27]
Wilms tumor	DISB6T16	Strong	Altered Expression	[28]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[29]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[29]
High blood pressure	DISY2OHH	moderate	Biomarker	[30]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[31]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[32]
Myelodysplastic syndrome	DISYHNUI	Disputed	Biomarker	[33]
Acute monocytic leukemia	DIS28NEL	Limited	Altered Expression	[34]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[35]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[36]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[37]
Neoplasm	DISZKGEW	Limited	Biomarker	[38]

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 Protein CBFA2T1 (RUNX1T1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein CBFA2T1 (RUNX1T1).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein CBFA2T1 (RUNX1T1).	[42]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein CBFA2T1 (RUNX1T1).	[43]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Protein CBFA2T1 (RUNX1T1).	[44]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Protein CBFA2T1 (RUNX1T1).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein CBFA2T1 (RUNX1T1).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein CBFA2T1 (RUNX1T1).	[46]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Protein CBFA2T1 (RUNX1T1).	[43]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Protein CBFA2T1 (RUNX1T1).	[47]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein CBFA2T1 (RUNX1T1).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein CBFA2T1 (RUNX1T1).	[49]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Protein CBFA2T1 (RUNX1T1).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Protein CBFA2T1 (RUNX1T1).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein CBFA2T1 (RUNX1T1).	[48]

References

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