Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBP2QQ2)

• DOT Name: Endothelial transcription factor GATA-2 (GATA2)
• Synonyms: GATA-binding protein 2
• Gene Name: GATA2
• Related Disease:
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
  Deafness-lymphedema-leukemia syndrome
  GATA2 deficiency with susceptibility to MDS/AML
  Monocytopenia with susceptibility to infections
  Acquired aplastic anemia
  Acute myelogenous leukaemia
  Acute myelomonocytic leukemia M4
  Adenoma
  Advanced cancer
  Anemia
  Aplastic anemia
  Arteriosclerosis
  Bone marrow failure syndrome
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Fungal lung infectious disease
  Haematological malignancy
  Hepatocellular carcinoma
  Idiopathic thrombocytopenic purpura
  Leukemia
  Leukopenia
  Lung cancer
  Mycobacterium infection
  Myelodysplastic syndrome
  Myeloid leukaemia
  Non-small-cell lung cancer
  Pancytopenia
  Prostate cancer
  Prostate carcinoma
  Sensorineural hearing loss disorder
  Trichohepatoenteric syndrome
  Wilms tumor
  Breast cancer
  Breast carcinoma
  Lung carcinoma
  Lymphedema
  leukaemia
  Acute monocytic leukemia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Childhood myelodysplastic syndrome
  Gastric cancer
  Lymphatic malformation 1
  Severe congenital neutropenia
• UniProt ID: GATA2_HUMAN
• PDB ID: 5O9B; 6ZFV
• Pfam ID: PF00320
• Sequence:
  MEVAPEQPRWMAHPAVLNAQHPDSHHPGLAHNYMEPAQLLPPDEVDVFFNHLDSQGNPYY
  ANPAHARARVSYSPAHARLTGGQMCRPHLLHSPGLPWLDGGKAALSAAAAHHHNPWTVSP
  FSKTPLHPSAAGGPGGPLSVYPGAGGGSGGGSGSSVASLTPTAAHSGSHLFGFPPTPPKE
  VSPDPSTTGAASPASSSAGGSAARGEDKDGVKYQVSLTESMKMESGSPLRPGLATMGTQP
  ATHHPIPTYPSYVPAAAHDYSSGLFHPGGFLGGPASSFTPKQRSKARSCSEGRECVNCGA
  TATPLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPKRRLSAARRAGTCCANCQTTTTTLW
  RRNANGDPVCNACGLYYKLHNVNRPLTMKKEGIQTRNRKMSNKSKKSKKGAECFEELSKC
  MQEKSSPFSAAALAGHMAPVGHLPPFSHSGHILPTPTPIHPSSSLSFGHPHPSSMVTAMG
• Function: Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'.
• Tissue Specificity: Endothelial cells.
• Reactome Pathway:
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Genetic Variation	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Genetic Variation	[1]
Deafness-lymphedema-leukemia syndrome	DISM514S	Definitive	Autosomal dominant	[2]
GATA2 deficiency with susceptibility to MDS/AML	DISDOU6F	Definitive	Autosomal dominant	[3]
Monocytopenia with susceptibility to infections	DISN42Z1	Definitive	Autosomal dominant	[4]
Acquired aplastic anemia	DISCMKMX	Strong	Genetic Variation	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Autosomal dominant	[6]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[7]
Adenoma	DIS78ZEV	Strong	Altered Expression	[8]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[9]
Anemia	DISTVL0C	Strong	Altered Expression	[10]
Aplastic anemia	DISJRSC0	Strong	Altered Expression	[11]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[12]
Bone marrow failure syndrome	DISVUY1J	Strong	Genetic Variation	[13]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Altered Expression	[14]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Altered Expression	[14]
Fungal lung infectious disease	DISH0JV6	Strong	Biomarker	[15]
Haematological malignancy	DISCDP7W	Strong	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Altered Expression	[18]
Leukemia	DISNAKFL	Strong	Altered Expression	[19]
Leukopenia	DISJMBMM	Strong	Altered Expression	[20]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[21]
Mycobacterium infection	DISNSMUD	Strong	Genetic Variation	[22]
Myelodysplastic syndrome	DISYHNUI	Strong	Autosomal dominant	[6]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[24]
Pancytopenia	DISVKEHV	Strong	Genetic Variation	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Altered Expression	[20]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[26]
Wilms tumor	DISB6T16	Strong	Biomarker	[27]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[28]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[28]
Lung carcinoma	DISTR26C	moderate	Posttranslational Modification	[21]
Lymphedema	DISRJKTS	moderate	Biomarker	[29]
leukaemia	DISS7D1V	Disputed	Altered Expression	[19]
Acute monocytic leukemia	DIS28NEL	Limited	Genetic Variation	[30]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Limited	Genetic Variation	[31]
Childhood myelodysplastic syndrome	DISMN80I	Limited	Genetic Variation	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Lymphatic malformation 1	DIS857QZ	Limited	Genetic Variation	[34]
Severe congenital neutropenia	DISES99N	Limited	Genetic Variation	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Endothelial transcription factor GATA-2 (GATA2).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[43]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[44]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[45]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[47]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[48]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[49]
Pomalidomide	DMTGBAX	Approved	Pomalidomide decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[50]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[46]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[37]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[48]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[45]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[58]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[52]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX decreases the expression of Endothelial transcription factor GATA-2 (GATA2).	[48]
Chebulinic acid	DMR8HKC	Investigative	Chebulinic acid increases the expression of Endothelial transcription factor GATA-2 (GATA2).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Endothelial transcription factor GATA-2 (GATA2).	[53]

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