Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT501PY9)

• DOT Name: Polyphosphoinositide phosphatase (FIG4)
• Synonyms: EC 3.1.3.-; EC 3.1.3.36; EC 3.1.3.86; Phosphatidylinositol 3,5-bisphosphate 5-phosphatase; SAC domain-containing protein 3; Serine-protein phosphatase FIG4; EC 3.1.3.16
• Gene Name: FIG4
• Related Disease:
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type 4J
  Microcephalic primordial dwarfism due to RTTN deficiency
  Amyotrophic lateral sclerosis type 1
  Amyotrophic lateral sclerosis type 11
  Charcot-Marie-Tooth disease type 1
  Charcot-Marie-Tooth disease type 1A
  Charcot-Marie-Tooth disease type 1B
  Charcot-Marie-Tooth disease type 2
  Epilepsy
  Hereditary motor and sensory neuropathy
  Hypopigmentation of the skin
  Lateral sclerosis
  Malignant glioma
  Motor neurone disease
  Peripheral neuropathy
  Yunis-Varon syndrome
  High blood pressure
  Papillon-Lefevre disease
  Amyotrophic lateral sclerosis
  Bilateral parasagittal parieto-occipital polymicrogyria
  Breast cancer
  Breast carcinoma
  Charcot-Marie-Tooth disease type 3
  Charcot-Marie-Tooth disease type 4
  Demyelinating polyneuropathy
  Lysosomal storage disease
  Neuroblastoma
• UniProt ID: FIG4_HUMAN
• PDB ID: 7K1W
• EC Number: 3.1.3.-; 3.1.3.16; 3.1.3.36; 3.1.3.86
• Pfam ID: PF02383
• Sequence:
  MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVIIDDRHVYTQ
  QEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEGYYIVLITKRRKMADIG
  GHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQNVDLSSNFYFSYSYDLSHSLQYNLT
  VLRMPLEMLKSEMTQNRQESFDIFEDEGLITQGGSGVFGICSEPYMKYVWNGELLDIIKS
  TVHRDWLLYIIHGFCGQSKLLIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVE
  TEQILCDASVMSFTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALH
  FDQMFQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPWDMAK
  YTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELGGCVIPTGRLQTG
  ILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNLQFDTDAVRLFEELYEDHGDT
  LSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQTLSRYYSNAFSDADRQDSINLFLGVFHP
  TEGKPHLWELPTDFYLHHKNTMRLLPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLI
  VKKFHKYEEEIDIHNEFFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDE
  TGKSVLGNKSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVK
  MTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQDKNSQQPCS
  RCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQGIMQPLGKEDSSMYRE
  YIRNRYL
• Function: Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the dephosphorylation of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) to form phosphatidylinositol 3-phosphate. Has serine-protein phosphatase activity acting on PIKfyve to stimulate its lipid kinase activity, its catalytically activity being required for maximal PI(3,5)P2 production. In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide and although displaying preferences for PtdIns(3,5)P2, it is capable of hydrolyzing PtdIns(3,4,5)P3 and PtdIns(4,5)P2, at least in vitro.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Synthesis of PIPs at the early endosome membrane (R-HSA-1660516)
  Synthesis of PIPs at the late endosome membrane (R-HSA-1660517)
  Synthesis of PIPs at the Golgi membrane (R-HSA-1660514)
• BioCyc Pathway: MetaCyc:HS12771-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot marie tooth disease	DIS3BT2L	Definitive	Autosomal recessive	[1]
Charcot-Marie-Tooth disease type 4J	DIS23T23	Definitive	Autosomal recessive	[2]
Microcephalic primordial dwarfism due to RTTN deficiency	DIS25LK9	Definitive	Genetic Variation	[3]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Genetic Variation	[4]
Amyotrophic lateral sclerosis type 11	DISITB5O	Strong	Autosomal dominant	[2]
Charcot-Marie-Tooth disease type 1	DIS56F9A	Strong	Biomarker	[5]
Charcot-Marie-Tooth disease type 1A	DISSRZG7	Strong	Biomarker	[5]
Charcot-Marie-Tooth disease type 1B	DISJRS1V	Strong	Biomarker	[5]
Charcot-Marie-Tooth disease type 2	DISR30O9	Strong	Biomarker	[5]
Epilepsy	DISBB28L	Strong	Genetic Variation	[6]
Hereditary motor and sensory neuropathy	DISR0X2K	Strong	Biomarker	[7]
Hypopigmentation of the skin	DIS39YKC	Strong	Genetic Variation	[8]
Lateral sclerosis	DISH30B8	Strong	Genetic Variation	[4]
Malignant glioma	DISFXKOV	Strong	Biomarker	[9]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[10]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[11]
Yunis-Varon syndrome	DISKC6IE	Strong	Autosomal recessive	[12]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[13]
Papillon-Lefevre disease	DIS3R7KX	moderate	Biomarker	[14]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[15]
Bilateral parasagittal parieto-occipital polymicrogyria	DISN02H0	Supportive	Autosomal recessive	[16]
Breast cancer	DIS7DPX1	Limited	Biomarker	[17]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[17]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Biomarker	[7]
Charcot-Marie-Tooth disease type 4	DISM8IZN	Limited	CausalMutation	[18]
Demyelinating polyneuropathy	DIS7IO4W	Limited	Biomarker	[19]
Lysosomal storage disease	DIS6QM6U	Limited	Biomarker	[20]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[21]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Polyphosphoinositide phosphatase (FIG4) affects the response to substance of Topotecan.	[36]

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 Polyphosphoinositide phosphatase (FIG4).	[22]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Polyphosphoinositide phosphatase (FIG4).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Polyphosphoinositide phosphatase (FIG4).	[33]

13 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 Polyphosphoinositide phosphatase (FIG4).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Polyphosphoinositide phosphatase (FIG4).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polyphosphoinositide phosphatase (FIG4).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Polyphosphoinositide phosphatase (FIG4).	[30]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polyphosphoinositide phosphatase (FIG4).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[34]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Polyphosphoinositide phosphatase (FIG4).	[35]

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