Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN3A6CN)

• DOT Name: Ribose-phosphate pyrophosphokinase 1 (PRPS1)
• Synonyms: EC 2.7.6.1; PPRibP; Phosphoribosyl pyrophosphate synthase I; PRS-I
• Gene Name: PRPS1
• Related Disease:
  Advanced cancer
  Arts syndrome
  Charcot-Marie-Tooth disease X-linked recessive 5
  Hearing loss, X-linked 1
  Phosphoribosylpyrophosphate synthetase superactivity
  PRPS1 deficiency disorder
  Acute lymphocytic leukaemia
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type X
  Colorectal carcinoma
  Deafness
  Diabetes insipidus
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hutchinson-Gilford progeria syndrome
  Inherited retinal dystrophy
  Metabolic disorder
  Neoplasm
  Neurodegeneration with brain iron accumulation
  Peripheral neuropathy
  Polyneuropathy
  Sensorineural hearing loss disorder
  Mild phosphoribosylpyrophosphate synthetase superactivity
  Severe phosphoribosylpyrophosphate synthetase superactivity
  X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome
  X-linked nonsyndromic hearing loss
  Childhood acute lymphoblastic leukemia
  Neuroblastoma
  Optic nerve disorder
  X-linked mixed hearing loss with perilymphatic gusher
• UniProt ID: PRPS1_HUMAN
• PDB ID: 2H06; 2H07; 2H08; 2HCR; 3EFH; 3S5J; 4F8E; 4LYG; 4LZN; 4LZO; 4M0P; 4M0U; 8DBC; 8DBD; 8DBE; 8DBF; 8DBG; 8DBH; 8DBI; 8DBJ; 8DBK; 8DBL; 8DBM; 8DBN; 8DBO
• EC Number: 2.7.6.1
• Pfam ID: PF14572 ; PF13793
• Sequence:
  MPNIKIFSGSSHQDLSQKIADRLGLELGKVVTKKFSNQETCVEIGESVRGEDVYIVQSGC
  GEINDNLMELLIMINACKIASASRVTAVIPCFPYARQDKKDKSRAPISAKLVANMLSVAG
  ADHIITMDLHASQIQGFFDIPVDNLYAEPAVLKWIRENISEWRNCTIVSPDAGGAKRVTS
  IADRLNVDFALIHKERKKANEVDRMVLVGDVKDRVAILVDDMADTCGTICHAADKLLSAG
  ATRVYAILTHGIFSGPAISRINNACFEAVVVTNTIPQEDKMKHCSKIQVIDISMILAEAI
  RRTHNGESVSYLFSHVPL
• Function: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: 5-Phosphoribose 1-diphosphate biosynthesis (R-HSA-73843)
• BioCyc Pathway: MetaCyc:HS07410-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Arts syndrome	DIS8LNCN	Definitive	X-linked	[2]
Charcot-Marie-Tooth disease X-linked recessive 5	DISTOGMP	Definitive	X-linked recessive	[3]
Hearing loss, X-linked 1	DISHL7OQ	Definitive	X-linked	[4]
Phosphoribosylpyrophosphate synthetase superactivity	DISD5WC1	Definitive	X-linked	[5]
PRPS1 deficiency disorder	DIS21O0T	Definitive	X-linked	[6]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[7]
Astrocytoma	DISL3V18	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[10]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[11]
Charcot-Marie-Tooth disease type X	DISVGD01	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[13]
Deafness	DISKCLH4	Strong	Genetic Variation	[14]
Diabetes insipidus	DIS0U6CJ	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[10]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Altered Expression	[16]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[17]
Metabolic disorder	DIS71G5H	Strong	Genetic Variation	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Neurodegeneration with brain iron accumulation	DISRK4DZ	Strong	Biomarker	[20]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[21]
Polyneuropathy	DISB9G3W	Strong	Biomarker	[21]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[22]
Mild phosphoribosylpyrophosphate synthetase superactivity	DISN0ZAK	Supportive	X-linked	[23]
Severe phosphoribosylpyrophosphate synthetase superactivity	DISM8343	Supportive	X-linked	[23]
X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome	DIS4JW1U	Supportive	X-linked	[24]
X-linked nonsyndromic hearing loss	DISSWCJS	Supportive	X-linked	[25]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Biomarker	[7]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[26]
Optic nerve disorder	DISSOQM8	Limited	Biomarker	[21]
X-linked mixed hearing loss with perilymphatic gusher	DISA86GW	Limited	Biomarker	[15]

20 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 Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[35]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[36]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[37]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[38]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[39]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[40]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[29]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[44]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ribose-phosphate pyrophosphokinase 1 (PRPS1).	[43]

References

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