Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5PJZV)

• DOT Name: Paired box protein Pax-3 (PAX3)
• Synonyms: HuP2
• Gene Name: PAX3
• Related Disease:
  Craniofacial-deafness-hand syndrome
  Deafness
  Waardenburg syndrome
  Waardenburg syndrome type 1
  Waardenburg syndrome type 2
  Bone osteosarcoma
  Congenital nervous system disorder
  Ewing sarcoma
  Glioma
  Leukemia
  Malignant soft tissue neoplasm
  Medulloblastoma
  Melanocytic nevus
  Metastatic melanoma
  Neuroblastoma
  Osteosarcoma
  Piebaldism
  Primary biliary cholangitis
  Sarcoma
  Sensorineural hearing loss disorder
  Small-cell lung cancer
  Soft tissue neoplasm
  Synovial sarcoma
  Waardenburg syndrome type 3
  Cutaneous melanoma
  Gastric cancer
  Hirschsprung disease
  Stomach cancer
  Alopecia
  Aniridia
  Intellectual disability
  Microphthalmia with limb anomalies
• UniProt ID: PAX3_HUMAN
• PDB ID: 3CMY
• Pfam ID: PF00046 ; PF00292 ; PF12360
• Sequence:
  MTTLAGAVPRMMRPGPGQNYPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHKIV
  EMAHHGIRPCVISRQLRVSHGCVSKILCRYQETGSIRPGAIGGSKPKQVTTPDVEKKIEE
  YKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERKEAEES
  EKKAKHSIDGILSERASAPQSDEGSDIDSEPDLPLKRKQRRSRTTFTAEQLEELERAFER
  THYPDIYTREELAQRAKLTEARVQVWFSNRRARWRKQAGANQLMAFNHLIPGGFPPTAMP
  TLPTYQLSETSYQPTSIPQAVSDPSSTVHRPQPLPPSTVHQSTIPSNPDSSSAYCLPSTR
  HGFSSYTDSFVPPSGPSNPMNPTIGNGLSPQVMGLLTNHGGVPHQPQTDYALSPLTGGLE
  PTTTVSASCSQRLDHMKSLDSLPTSQSYCPPTYSTTGYSMDPVTGYQYGQYGQSKPWTF
• Function: Transcription factor that may regulate cell proliferation, migration and apoptosis. Involved in neural development and myogenesis. Transcriptional activator of MITF, acting synergistically with SOX10.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniofacial-deafness-hand syndrome	DISZ1RQ0	Definitive	Autosomal dominant	[1]
Deafness	DISKCLH4	Definitive	Biomarker	[2]
Waardenburg syndrome	DISRU41A	Definitive	Autosomal dominant	[3]
Waardenburg syndrome type 1	DIS8DBQ5	Definitive	Autosomal dominant	[4]
Waardenburg syndrome type 2	DISVZBEV	Definitive	Genetic Variation	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Congenital nervous system disorder	DIS2BIP8	Strong	Biomarker	[7]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[9]
Leukemia	DISNAKFL	Strong	Biomarker	[10]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[11]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[12]
Melanocytic nevus	DISYS32D	Strong	Biomarker	[13]
Metastatic melanoma	DISSL43L	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[15]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Piebaldism	DISDLDF2	Strong	Genetic Variation	[16]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[17]
Sarcoma	DISZDG3U	Strong	Biomarker	[11]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[18]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[19]
Soft tissue neoplasm	DISP2OHE	Strong	Genetic Variation	[20]
Synovial sarcoma	DISEZJS7	Strong	Genetic Variation	[21]
Waardenburg syndrome type 3	DIS4JF16	Strong	Autosomal recessive	[22]
Cutaneous melanoma	DIS3MMH9	moderate	Altered Expression	[23]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[24]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[25]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[24]
Alopecia	DIS37HU4	Limited	Genetic Variation	[26]
Aniridia	DIS1P333	Limited	Genetic Variation	[27]
Intellectual disability	DISMBNXP	Limited	Biomarker	[28]
Microphthalmia with limb anomalies	DIS19E4H	Limited	GermlineCausalMutation	[22]

22 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 Paired box protein Pax-3 (PAX3).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Paired box protein Pax-3 (PAX3).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Paired box protein Pax-3 (PAX3).	[31]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Paired box protein Pax-3 (PAX3).	[32]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Paired box protein Pax-3 (PAX3).	[34]
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the expression of Paired box protein Pax-3 (PAX3).	[35]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Paired box protein Pax-3 (PAX3).	[36]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Abacavir	DMMN36E	Approved	Abacavir decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Dabigatran	DMDI6R4	Approved	Dabigatran decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Paired box protein Pax-3 (PAX3).	[34]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Paired box protein Pax-3 (PAX3).	[37]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Paired box protein Pax-3 (PAX3).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Paired box protein Pax-3 (PAX3).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Paired box protein Pax-3 (PAX3).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Paired box protein Pax-3 (PAX3).	[41]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Paired box protein Pax-3 (PAX3).	[42]
Hydroxyacetic acid	DMQFBH6	Investigative	Hydroxyacetic acid decreases the expression of Paired box protein Pax-3 (PAX3).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Paired box protein Pax-3 (PAX3).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Paired box protein Pax-3 (PAX3).	[40]

References

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• [23] Pax3 transcripts in melanoblast development.Dev Growth Differ. 2005 Dec;47(9):627-35. doi: 10.1111/j.1440-169X.2005.00835.x.
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