Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3IRZH3)

• DOT Name: Guanine nucleotide-binding protein subunit alpha-12 (GNA12)
• Synonyms: G alpha-12; G-protein subunit alpha-12
• Gene Name: GNA12
• Related Disease:
  Adult lymphoma
  Cervical cancer
  Cervical carcinoma
  Cutaneous melanoma
  Lymphoma
  Pediatric lymphoma
  Tuberculosis
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  B-cell lymphoma
  Breast neoplasm
  Carcinoma of esophagus
  Cardiac failure
  Congestive heart failure
  Epithelial ovarian cancer
  Esophageal cancer
  Hepatitis B virus infection
  Hepatocellular carcinoma
  High blood pressure
  Metastatic malignant neoplasm
  Multi-drug resistant tuberculosis
  Multiple endocrine neoplasia type 1
  Myocardial ischemia
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Primary hyperparathyroidism
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Psychotic disorder
  Squamous cell carcinoma
  Colorectal carcinoma
  Nasopharyngeal carcinoma
  Acute myelogenous leukaemia
  Ankylosing spondylitis
  Breast cancer
  Breast carcinoma
  Crohn disease
  Inflammatory bowel disease
  Melanoma
  Psoriasis
  Rheumatoid arthritis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: GNA12_HUMAN
• PDB ID: 7YDJ
• Pfam ID: PF00503
• Sequence:
  MSGVVRTLSRCLLPAEAGGARERRAGSGARDAEREARRRSRDIDALLARERRAVRRLVKI
  LLLGAGESGKSTFLKQMRIIHGREFDQKALLEFRDTIFDNILKGSRVLVDARDKLGIPWQ
  YSENEKHGMFLMAFENKAGLPVEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVK
  YFLDNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQ
  CFDGITSILFMVSSSEYDQVLMEDRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDL
  LVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRNRSKPLFHHFTTAIDTENVR
  FVFHAVKDTILQENLKDIMLQ
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins. Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production. Inhibits CDH1-mediated cell adhesion in process independent from Rho activation. Together with NAPA promotes CDH5 localization to plasma membrane. May play a role in the control of cell migration through the TOR signaling cascade.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  cGMP-PKG sig.ling pathway (hsa04022)
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Vascular smooth muscle contraction (hsa04270)
  Long-term depression (hsa04730)
  Regulation of actin cytoskeleton (hsa04810)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Pathogenic Escherichia coli infection (hsa05130)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  G alpha (12/13) signalling events (R-HSA-416482)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Definitive	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Definitive	Altered Expression	[2]
Cutaneous melanoma	DIS3MMH9	Definitive	Biomarker	[3]
Lymphoma	DISN6V4S	Definitive	Altered Expression	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Altered Expression	[1]
Tuberculosis	DIS2YIMD	Definitive	Genetic Variation	[4]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[9]
Cardiac failure	DISDC067	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
High blood pressure	DISY2OHH	Strong	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[15]
Multi-drug resistant tuberculosis	DIS1A2CS	Strong	Biomarker	[16]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Biomarker	[17]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[11]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[21]
Primary hyperparathyroidism	DISB4U1Q	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[23]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[24]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[15]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[26]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[27]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Biomarker	[28]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[29]
Breast cancer	DIS7DPX1	Limited	Biomarker	[23]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[23]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[29]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[3]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[29]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[31]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[29]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[30]

10 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 Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[36]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[37]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[38]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[41]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[42]

1 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 affects the methylation of Guanine nucleotide-binding protein subunit alpha-12 (GNA12).	[40]

References

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