Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPA0QHW)

• DOT Name: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4)
• Synonyms: EC 3.1.4.11; Phosphoinositide phospholipase C-beta-4; Phospholipase C-beta-4; PLC-beta-4
• Gene Name: PLCB4
• Related Disease:
  Acute myelogenous leukaemia
  Auriculocondylar syndrome 2
  Myelodysplastic syndrome
  Absence epilepsy
  Adenocarcinoma
  Advanced cancer
  Analgesia
  Aural atresia, congenital
  Auriculocondylar syndrome 1
  Breast cancer
  Breast carcinoma
  Chagas disease
  Endometriosis
  Major depressive disorder
  Melanoma
  Mood disorder
  Bipolar disorder
  Gastrointestinal stromal tumour
  Schizoaffective disorder
  Schizophrenia
  Auriculocondylar syndrome
  46,XY sex reversal 2
  Charcot-Marie-Tooth disease type 3
  Neoplasm
  Uveal Melanoma
• UniProt ID: PLCB4_HUMAN
• EC Number: 3.1.4.11
• Pfam ID: PF00168 ; PF06631 ; PF09279 ; PF17787 ; PF00388 ; PF00387
• Sequence:
  MAKPYEFNWQKEVPSFLQEGAVFDRYEEESFVFEPNCLFKVDEFGFFLTWRSEGKEGQVL
  ECSLINSIRSGAIPKDPKILAALEAVGKSENDLEGRIVCVCSGTDLVNISFTYMVAENPE
  VTKQWVEGLRSIIHNFRANNVSPMTCLKKHWMKLAFMTNTNGKIPVRSITRTFASGKTEK
  VIFQALKELGLPSGKNDEIEPTAFSYEKFYELTQKICPRTDIEDLFKKINGDKTDYLTVD
  QLVSFLNEHQRDPRLNEILFPFYDAKRAMQIIEMYEPDEDLKKKGLISSDGFCRYLMSDE
  NAPVFLDRLELYQEMDHPLAHYFISSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCVELD
  CWDGKGEDQEPIITHGKAMCTDILFKDVIQAIKETAFVTSEYPVILSFENHCSKYQQYKM
  SKYCEDLFGDLLLKQALESHPLEPGRALPSPNDLKRKILIKNKRLKPEVEKKQLEALRSM
  MEAGESASPANILEDDNEEEIESADQEEEAHPEFKFGNELSADDLGHKEAVANSVKKGLV
  TVEDEQAWMASYKYVGATTNIHPYLSTMINYAQPVKFQGFHVAEERNIHYNMSSFNESVG
  LGYLKTHAIEFVNYNKRQMSRIYPKGGRVDSSNYMPQIFWNAGCQMVSLNYQTPDLAMQL
  NQGKFEYNGSCGYLLKPDFMRRPDRTFDPFSETPVDGVIAATCSVQVISGQFLSDKKIGT
  YVEVDMYGLPTDTIRKEFRTRMVMNNGLNPVYNEESFVFRKVILPDLAVLRIAVYDDNNK
  LIGQRILPLDGLQAGYRHISLRNEGNKPLSLPTIFCNIVLKTYVPDGFGDIVDALSDPKK
  FLSITEKRADQMRAMGIETSDIADVPSDTSKNDKKGKANTAKANVTPQSSSELRPTTTAA
  LASGVEAKKGIELIPQVRIEDLKQMKAYLKHLKKQQKELNSLKKKHAKEHSTMQKLHCTQ
  VDKIVAQYDKEKSTHEKILEKAMKKKGGSNCLEMKKETEIKIQTLTSDHKSKVKEIVAQH
  TKEWSEMINTHSAEEQEIRDLHLSQQCELLKKLLINAHEQQTQQLKLSHDRESKEMRAHQ
  AKISMENSKAISQDKSIKNKAERERRVRELNSSNTKKFLEERKRLAMKQSKEMDQLKKVQ
  LEHLEFLEKQNEQAKEMQQMVKLEAEMDRRPATVV
• Function: Activated phosphatidylinositol-specific phospholipase C enzymes catalyze the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in G-protein coupled receptor signaling pathways. PLCB4 is a direct effector of the endothelin receptor signaling pathway that plays an essential role in lower jaw and middle ear structures development.
• Tissue Specificity: Preferentially expressed in the retina.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Chemokine sig.ling pathway (hsa04062)
  Phosphatidylinositol sig.ling system (hsa04070)
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Wnt sig.ling pathway (hsa04310)
  Apelin sig.ling pathway (hsa04371)
  Gap junction (hsa04540)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  NOD-like receptor sig.ling pathway (hsa04621)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Glutamatergic sy.pse (hsa04724)
  Cholinergic sy.pse (hsa04725)
  Serotonergic sy.pse (hsa04726)
  Dopaminergic sy.pse (hsa04728)
  Long-term depression (hsa04730)
  Taste transduction (hsa04742)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Insulin secretion (hsa04911)
  GnRH sig.ling pathway (hsa04912)
  Estrogen sig.ling pathway (hsa04915)
  Melanogenesis (hsa04916)
  Thyroid hormone synthesis (hsa04918)
  Thyroid hormone sig.ling pathway (hsa04919)
  Oxytocin sig.ling pathway (hsa04921)
  Glucagon sig.ling pathway (hsa04922)
  Renin secretion (hsa04924)
  Aldosterone synthesis and secretion (hsa04925)
  Relaxin sig.ling pathway (hsa04926)
  Cortisol synthesis and secretion (hsa04927)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  GnRH secretion (hsa04929)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Cushing syndrome (hsa04934)
  Growth hormone synthesis, secretion and action (hsa04935)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
  Carbohydrate digestion and absorption (hsa04973)
  Alzheimer disease (hsa05010)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Shigellosis (hsa05131)
  Chagas disease (hsa05142)
  African trypanosomiasis (hsa05143)
  Amoebiasis (hsa05146)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  G alpha (q) signalling events (R-HSA-416476)
  PLC beta mediated events (R-HSA-112043)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Auriculocondylar syndrome 2	DIS6FF0Z	Definitive	Autosomal dominant	[2]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[1]
Absence epilepsy	DISJPOUD	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Analgesia	DISK3TVI	Strong	Biomarker	[6]
Aural atresia, congenital	DISCP7UV	Strong	Genetic Variation	[7]
Auriculocondylar syndrome 1	DIS5C8TJ	Strong	Autosomal dominant	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Chagas disease	DIS8KNVF	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Biomarker	[11]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[12]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[13]
Mood disorder	DISLVMWO	Strong	Biomarker	[12]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[14]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[15]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[14]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[14]
Auriculocondylar syndrome	DISW3W1P	Supportive	Autosomal dominant	[16]
46,XY sex reversal 2	DIS0USUN	Limited	Genetic Variation	[17]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Genetic Variation	[17]
Neoplasm	DISZKGEW	Limited	Biomarker	[18]
Uveal Melanoma	DISA7ZGL	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4) affects the response to substance of Mitoxantrone.	[32]

1 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 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[25]
Selenium	DM25CGV	Approved	Selenium decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[26]
Malathion	DMXZ84M	Approved	Malathion increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[27]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[28]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4).	[31]

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