Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYZ1ZI0)

• DOT Name: Guanine nucleotide-binding protein subunit alpha-14 (GNA14)
• Synonyms: G alpha-14; G-protein subunit alpha-14
• Gene Name: GNA14
• Related Disease:
  Cholelithiasis
  Hemangioma
  High blood pressure
  Langerhans cell histiocytosis
  Neoplasm
  Endometrial carcinoma
  Hashimoto thyroiditis
  Hepatocellular carcinoma
  Melanoma
  Temporal lobe epilepsy
• UniProt ID: GNA14_HUMAN
• Pfam ID: PF00503
• Sequence:
  MAGCCCLSAEEKESQRISAEIERQLRRDKKDARRELKLLLLGTGESGKSTFIKQMRIIHG
  SGYSDEDRKGFTKLVYQNIFTAMQAMIRAMDTLRIQYVCEQNKENAQIIREVEVDKVSML
  SREQVEAIKQLWQDPGIQECYDRRREYQLSDSAKYYLTDIDRIATPSFVPTQQDVLRVRV
  PTTGIIEYPFDLENIIFRMVDVGGQRSERRKWIHCFESVTSIIFLVALSEYDQVLAECDN
  ENRMEESKALFKTIITYPWFLNSSVILFLNKKDLLEEKIMYSHLISYFPEYTGPKQDVRA
  ARDFILKLYQDQNPDKEKVIYSHFTCATDTDNIRFVFAAVKDTILQLNLREFNLV
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Chagas disease (hsa05142)
  Amoebiasis (hsa05146)
• Reactome Pathway:
  G-protein activation (R-HSA-202040)
  Acetylcholine regulates insulin secretion (R-HSA-399997)
  G alpha (q) signalling events (R-HSA-416476)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  Thromboxane signalling through TP receptor (R-HSA-428930)
  Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion (R-HSA-434316)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  PLC beta mediated events (R-HSA-112043)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[1]
Hemangioma	DISDCGAG	Strong	Genetic Variation	[2]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Langerhans cell histiocytosis	DISDQSW3	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	moderate	Genetic Variation	[5]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[6]
Hashimoto thyroiditis	DIS77CDF	Limited	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[8]
Melanoma	DIS1RRCY	Limited	Biomarker	[6]
Temporal lobe epilepsy	DISNOPXX	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Guanine nucleotide-binding protein subunit alpha-14 (GNA14).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Guanine nucleotide-binding protein subunit alpha-14 (GNA14).	[10]

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 increases the methylation of Guanine nucleotide-binding protein subunit alpha-14 (GNA14).	[11]

References

• [1] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [2] High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms.Mod Pathol. 2019 Nov;32(11):1657-1665. doi: 10.1038/s41379-019-0284-y. Epub 2019 Jun 12.
• [3] G Protein Subunit 14 Mediates Fibroblast Growth Factor 2-Induced Cellular Responses in Human Endothelial Cells.J Cell Physiol. 2019 Jul;234(7):10184-10195. doi: 10.1002/jcp.27688. Epub 2018 Nov 1.
• [4] GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation.Am J Hum Genet. 2016 Aug 4;99(2):443-50. doi: 10.1016/j.ajhg.2016.06.010. Epub 2016 Jul 28.
• [5] GNA11 joins GNAQ and GNA14 as a recurrently mutated gene in anastomosing hemangioma.Virchows Arch. 2020 Mar;476(3):475-481. doi: 10.1007/s00428-019-02673-y. Epub 2019 Nov 9.
• [6] GNA14 silencing suppresses the proliferation of endometrial carcinoma cells through inducing apoptosis and G(2)/M cell cycle arrest.Biosci Rep. 2018 Sep 7;38(5):BSR20180574. doi: 10.1042/BSR20180574. Print 2018 Oct 31.
• [7] Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis.J Endocrinol Invest. 2019 May;42(5):567-576. doi: 10.1007/s40618-018-0955-4. Epub 2018 Oct 3.
• [8] Aberrantly DNA Methylated-Differentially Expressed Genes and Pathways in Hepatocellular Carcinoma.J Cancer. 2019 Jan 1;10(2):355-366. doi: 10.7150/jca.27832. eCollection 2019.
• [9] Familial temporal lobe epilepsy as a presenting feature of choreoacanthocytosis.Epilepsia. 2005 Aug;46(8):1256-63. doi: 10.1111/j.1528-1167.2005.65804.x.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.