Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGVC9MY)

• DOT Name: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)
• Synonyms: EC 3.1.4.11; Phosphoinositide phospholipase C-gamma-2; Phospholipase C-IV; PLC-IV; Phospholipase C-gamma-2; PLC-gamma-2
• Gene Name: PLCG2
• Related Disease:
  Hepatocellular carcinoma
  Rheumatoid arthritis
  Advanced cancer
  Alzheimer disease
  Autoimmune disease
  Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation
  B-cell lymphoma
  Burkitt lymphoma
  Candidiasis
  Crohn disease
  Familial Alzheimer disease
  Familial cold autoinflammatory syndrome 3
  Inflammatory bowel disease
  Kidney neoplasm
  Neoplasm
  Venous thromboembolism
  Acute lymphocytic leukaemia
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cherubism
  Coronary heart disease
  Leukemia
  Osteosarcoma
  Gastric neoplasm
  Acute myelogenous leukaemia
  Age-related macular degeneration
  Childhood kidney Wilms tumor
  Familial adenomatous polyposis
  Immune system disorder
  Lewy body dementia
  Lymphoma
  Progressive supranuclear palsy
  Richter syndrome
  Ulcerative colitis
  Waldenstrom macroglobulinemia
  Wilms tumor
• UniProt ID: PLCG2_HUMAN
• PDB ID: 2K2J; 2W2W; 2W2X
• EC Number: 3.1.4.11
• Pfam ID: PF00168 ; PF16457 ; PF00388 ; PF00387 ; PF00017 ; PF00018
• Sequence:
  MSTTVNVDSLAEYEKSQIKRALELGTVMTVFSFRKSTPERRTVQVIMETRQVAWSKTADK
  IEGFLDIMEIKEIRPGKNSKDFERAKAVRQKEDCCFTILYGTQFVLSTLSLAADSKEDAV
  NWLSGLKILHQEAMNASTPTIIESWLRKQIYSVDQTRRNSISLRELKTILPLINFKVSSA
  KFLKDKFVEIGAHKDELSFEQFHLFYKKLMFEQQKSILDEFKKDSSVFILGNTDRPDASA
  VYLHDFQRFLIHEQQEHWAQDLNKVRERMTKFIDDTMRETAEPFLFVDEFLTYLFSRENS
  IWDEKYDAVDMQDMNNPLSHYWISSSHNTYLTGDQLRSESSPEAYIRCLRMGCRCIELDC
  WDGPDGKPVIYHGWTRTTKIKFDDVVQAIKDHAFVTSSFPVILSIEEHCSVEQQRHMAKA
  FKEVFGDLLLTKPTEASADQLPSPSQLREKIIIKHKKLGPRGDVDVNMEDKKDEHKQQGE
  LYMWDSIDQKWTRHYCAIADAKLSFSDDIEQTMEEEVPQDIPPTELHFGEKWFHKKVEKR
  TSAEKLLQEYCMETGGKDGTFLVRESETFPNDYTLSFWRSGRVQHCRIRSTMEGGTLKYY
  LTDNLTFSSIYALIQHYRETHLRCAEFELRLTDPVPNPNPHESKPWYYDSLSRGEAEDML
  MRIPRDGAFLIRKREGSDSYAITFRARGKVKHCRINRDGRHFVLGTSAYFESLVELVSYY
  EKHSLYRKMRLRYPVTPELLERYNMERDINSLYDVSRMYVDPSEINPSMPQRTVKALYDY
  KAKRSDELSFCRGALIHNVSKEPGGWWKGDYGTRIQQYFPSNYVEDISTADFEELEKQII
  EDNPLGSLCRGILDLNTYNVVKAPQGKNQKSFVFILEPKQQGDPPVEFATDRVEELFEWF
  QSIREITWKIDTKENNMKYWEKNQSIAIELSDLVVYCKPTSKTKDNLENPDFREIRSFVE
  TKADSIIRQKPVDLLKYNQKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKY
  MQMNHALFSLNGRTGYVLQPESMRTEKYDPMPPESQRKILMTLTVKVLGARHLPKLGRSI
  ACPFVEVEICGAEYDNNKFKTTVVNDNGLSPIWAPTQEKVTFEIYDPNLAFLRFVVYEED
  MFSDPNFLAHATYPIKAVKSGFRSVPLKNGYSEDIELASLLVFCEMRPVLESEEELYSSC
  RQLRRRQEELNNQLFLYDTHQNLRNANRDALVKEFSVNENQLQLYQEKCNKRLREKRVSN
  SKFYS
• Function: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Calcium sig.ling pathway (hsa04020)
  Chemokine sig.ling pathway (hsa04062)
  NF-kappa B sig.ling pathway (hsa04064)
  HIF-1 sig.ling pathway (hsa04066)
  Phosphatidylinositol sig.ling system (hsa04070)
  Phospholipase D sig.ling pathway (hsa04072)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  C-type lectin receptor sig.ling pathway (hsa04625)
  .tural killer cell mediated cytotoxicity (hsa04650)
  B cell receptor sig.ling pathway (hsa04662)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin sig.ling pathway (hsa04722)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Thyroid hormone sig.ling pathway (hsa04919)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Growth hormone synthesis, secretion and action (hsa04935)
  Vibrio cholerae infection (hsa05110)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Shigellosis (hsa05131)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Glioma (hsa05214)
  Non-small cell lung cancer (hsa05223)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  Generation of second messenger molecules (R-HSA-202433)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  DAP12 signaling (R-HSA-2424491)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Dectin-2 family (R-HSA-5621480)
  Erythropoietin activates Phospholipase C gamma (PLCG) (R-HSA-9027277)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  Potential therapeutics for SARS (R-HSA-9679191)
  Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  GPVI-mediated activation cascade (R-HSA-114604)
• BioCyc Pathway: MetaCyc:HS06773-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation	DISUA10A	Strong	Autosomal dominant	[6]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[7]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[8]
Candidiasis	DISIRYMU	Strong	Biomarker	[9]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[10]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[11]
Familial cold autoinflammatory syndrome 3	DIS8YTYV	Strong	Autosomal dominant	[12]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[13]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[16]
Acute lymphocytic leukaemia	DISPX75S	moderate	Biomarker	[17]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[18]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[19]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[19]
Cherubism	DISHLJI0	moderate	Biomarker	[20]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[21]
Leukemia	DISNAKFL	moderate	Biomarker	[17]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[18]
Gastric neoplasm	DISOKN4Y	Disputed	Genetic Variation	[22]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[23]
Age-related macular degeneration	DIS0XS2C	Limited	Biomarker	[24]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Altered Expression	[25]
Familial adenomatous polyposis	DISW53RE	Limited	Altered Expression	[25]
Immune system disorder	DISAEGPH	Limited	Genetic Variation	[4]
Lewy body dementia	DISAE66J	Limited	Genetic Variation	[26]
Lymphoma	DISN6V4S	Limited	Biomarker	[27]
Progressive supranuclear palsy	DISO5KRQ	Limited	Genetic Variation	[26]
Richter syndrome	DISBX2TK	Limited	Genetic Variation	[28]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[13]
Waldenstrom macroglobulinemia	DIS9O23I	Limited	Altered Expression	[7]
Wilms tumor	DISB6T16	Limited	Altered Expression	[25]

18 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 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[32]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[32]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[34]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[35]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[36]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[41]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[43]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[44]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[40]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[40]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion decreases the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the phosphorylation of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[33]
Ibrutinib	DMHZCPO	Approved	Ibrutinib decreases the phosphorylation of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[45]
Fmet-leu-phe	DMQ391A	Investigative	Fmet-leu-phe increases the phosphorylation of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2).	[46]

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