Details of Drug Off-Target (DOT)

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

• DOT Name: Pituitary homeobox 2 (PITX2)
• Synonyms: ALL1-responsive protein ARP1; Homeobox protein PITX2; Paired-like homeodomain transcription factor 2; RIEG bicoid-related homeobox transcription factor; Solurshin
• Gene Name: PITX2
• Related Disease:
  Anterior segment dysgenesis 4
  Appendicitis
  Axenfeld-Rieger syndrome type 1
  Peters anomaly
  Ring dermoid of cornea
  Advanced cancer
  Al-Raqad syndrome
  Alzheimer disease
  Arrhythmia
  Breast neoplasm
  Cardiovascular disease
  Congenital glaucoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Fuchs' endothelial dystrophy
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  High blood pressure
  Hypothyroidism
  Juvenile open angle glaucoma
  Lung adenocarcinoma
  Nervous system disease
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Polycystic kidney disease
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Stroke
  Tooth agenesis
  Urinary bladder cancer
  Aniridia
  Clear cell renal carcinoma
  Familial adenomatous polyposis
  Glaucoma/ocular hypertension
  Axenfeld anomaly
  Axenfeld-Rieger syndrome
  Familial atrial fibrillation
  Rieger anomaly
  Cardiac failure
  Cataract
  Colorectal carcinoma
  Congestive heart failure
  Schizophrenia
  Tetralogy of fallot
• UniProt ID: PITX2_HUMAN
• PDB ID: 2L7F; 2L7M; 2LKX
• Pfam ID: PF00046 ; PF03826
• Sequence:
  METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSPESRKEAASSKFFPRQHPGA
  NEKDKSQQGKNEDVGAEDPSKKKRQRRQRTHFTSQQLQELEATFQRNRYPDMSTREEIAV
  WTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGFGPQFNGLMQPYDDMYPGYSYNNWA
  AKGLTSASLSTKSFPFFNSMNVNPLSSQSMFSPPNSISSMSMSSSMVPSAVTGVPGSSLN
  SLNNLNNLSSPSLNSAVPTPACPYAPPTPPYVYRDTCNSSLASLRLKAKQHSSFGYASVQ
  NPASNLSACQYAVDRPV
• Function: May play a role in myoblast differentiation. When unphosphorylated, associates with an ELAVL1-containing complex, which stabilizes cyclin mRNA and ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation; [Isoform PTX2C]: Involved in the establishment of left-right asymmetry in the developing embryo.
• KEGG Pathway: TGF-beta sig.ling pathway (hsa04350)
• Reactome Pathway: TFAP2 (AP-2) family regulates transcription of other transcription factors (R-HSA-8866906)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anterior segment dysgenesis 4	DISSZ066	Definitive	Autosomal dominant	[1]
Appendicitis	DIS4GOLF	Definitive	Biomarker	[2]
Axenfeld-Rieger syndrome type 1	DISCJK7U	Definitive	Autosomal dominant	[3]
Peters anomaly	DISERK0M	Definitive	Autosomal dominant	[1]
Ring dermoid of cornea	DISI2QC5	Definitive	Autosomal dominant	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Al-Raqad syndrome	DISR2J8Q	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Arrhythmia	DISFF2NI	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[9]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[10]
Congenital glaucoma	DISHN3GO	Strong	Genetic Variation	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Genetic Variation	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Posttranslational Modification	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
High blood pressure	DISY2OHH	Strong	Biomarker	[17]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[18]
Juvenile open angle glaucoma	DISZ43T5	Strong	Biomarker	[19]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[20]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Posttranslational Modification	[24]
Prostate carcinoma	DISMJPLE	Strong	Posttranslational Modification	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[25]
Stroke	DISX6UHX	Strong	Biomarker	[26]
Tooth agenesis	DIS1PWC7	Strong	Genetic Variation	[27]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[28]
Aniridia	DIS1P333	Moderate	Autosomal dominant	[29]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[30]
Familial adenomatous polyposis	DISW53RE	moderate	Biomarker	[31]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Genetic Variation	[32]
Axenfeld anomaly	DIS15GVG	Supportive	Autosomal dominant	[33]
Axenfeld-Rieger syndrome	DIS6XY4L	Supportive	Autosomal dominant	[33]
Familial atrial fibrillation	DISL4AGF	Supportive	Autosomal dominant	[34]
Rieger anomaly	DISNBLZ5	Supportive	Autosomal dominant	[33]
Cardiac failure	DISDC067	Limited	Genetic Variation	[35]
Cataract	DISUD7SL	Limited	Biomarker	[36]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[37]
Congestive heart failure	DIS32MEA	Limited	Genetic Variation	[35]
Schizophrenia	DISSRV2N	Limited	Biomarker	[17]
Tetralogy of fallot	DISMHFNW	Limited	Biomarker	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pituitary homeobox 2 (PITX2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pituitary homeobox 2 (PITX2).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pituitary homeobox 2 (PITX2).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pituitary homeobox 2 (PITX2).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pituitary homeobox 2 (PITX2).	[41]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Pituitary homeobox 2 (PITX2).	[40]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pituitary homeobox 2 (PITX2).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pituitary homeobox 2 (PITX2).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pituitary homeobox 2 (PITX2).	[44]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Pituitary homeobox 2 (PITX2).	[43]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Pituitary homeobox 2 (PITX2).	[44]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Pituitary homeobox 2 (PITX2).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Pituitary homeobox 2 (PITX2).	[46]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Pituitary homeobox 2 (PITX2).	[47]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the expression of Pituitary homeobox 2 (PITX2).	[48]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Pituitary homeobox 2 (PITX2).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pituitary homeobox 2 (PITX2).	[51]

References

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