Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT32TR4C)

DOT Name	Growth hormone variant (GH2)
Synonyms	GH-V; Growth hormone 2; Placenta-specific growth hormone
Gene Name	GH2
Related Disease	Choriocarcinoma ( ) Adenoma ( ) Diabetic retinopathy ( ) Neoplasm ( ) Obesity ( ) Pre-eclampsia ( ) Seminoma ( ) Silver-Russell syndrome ( ) Trophoblastic neoplasm ( ) Pituitary tumor ( ) Adult lymphoma ( ) Lymphoma ( ) Non-insulin dependent diabetes ( ) Pediatric lymphoma ( )
UniProt ID	SOM2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00103
Sequence	MAAGSRTSLLLAFGLLCLSWLQEGSAFPTIPLSRLFDNAMLRARRLYQLAYDTYQEFEEA YILKEQKYSFLQNPQTSLCFSESIPTPSNRVKTQQKSNLELLRISLLLIQSWLEPVQLLR SVFANSLVYGASDSNVYRHLKDLEEGIQTLMWRLEDGSPRTGQIFNQSYSKFDTKSHNDD ALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF
Function	Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
Tissue Specificity	Expressed in the placenta.
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 ) Neuroactive ligand-receptor interaction (hsa04080 ) PI3K-Akt sig.ling pathway (hsa04151 ) JAK-STAT sig.ling pathway (hsa04630 ) Growth hormone synthesis, secretion and action (hsa04935 )
Reactome Pathway	Growth hormone receptor signaling (R-HSA-982772 ) Prolactin receptor signaling (R-HSA-1170546 )

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Choriocarcinoma	DISDBVNL	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[2]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Pre-eclampsia	DISY7Q29	Strong	Biomarker	[6]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[4]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[7]
Trophoblastic neoplasm	DISY8WKT	Strong	Altered Expression	[8]
Pituitary tumor	DISN67JD	moderate	Altered Expression	[9]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[10]
Lymphoma	DISN6V4S	Limited	Biomarker	[10]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[11]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[10]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Growth hormone variant (GH2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Growth hormone variant (GH2).	[13]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Growth hormone variant (GH2).	[14]
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References

1	Transcription factor FOXF1 regulates growth hormone variant gene expression.Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E947-51. doi: 10.1152/ajpendo.00128.2006. Epub 2006 Jun 13.
2	Expression of the growth hormone variant gene in human placenta.J Clin Endocrinol Metab. 1987 Mar;64(3):635-7. doi: 10.1210/jcem-64-3-635.
3	Somatolactogens and diabetic retinopathy.Growth Horm IGF Res. 2018 Aug;41:42-47. doi: 10.1016/j.ghir.2018.02.002. Epub 2018 Feb 6.
4	The testis-specific expression pattern of the growth hormone/placental lactogen (GH/PL) gene cluster changes with malignancy.Hum Pathol. 1999 Oct;30(10):1201-6. doi: 10.1016/s0046-8177(99)90038-2.
5	CCAAT-enhancer-binding protein (C/EBP) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.J Biol Chem. 2013 Aug 2;288(31):22849-61. doi: 10.1074/jbc.M113.474999. Epub 2013 Jun 19.
6	Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia.J Matern Fetal Neonatal Med. 2007 Sep;20(9):651-9. doi: 10.1080/14767050701463571.
7	Characterization of genomic variants in CSH1 and GH2, two candidate genes for Silver-Russell syndrome in 17q24-q25.Genet Test. 2003 Fall;7(3):259-63. doi: 10.1089/109065703322537304.
8	Detection of placental growth hormone variant and chorionic somatomammotropin ribonucleic acid expression in human trophoblastic neoplasms by reverse transcriptase-polymerase chain reaction.Endocrinology. 1994 Jun;134(6):2461-7. doi: 10.1210/endo.134.6.7515000.
9	Differential binding of rat pituitary-specific nuclear factors to the 5'-flanking region of pituitary and placental members of the human growth hormone gene family.Mol Cell Biochem. 1991 Aug 14;106(2):181-7. doi: 10.1007/BF00230184.
10	The human placental growth hormone variant is mitogenic for rat lymphoma Nb2 cells.Endocrinology. 1990 Feb;126(2):971-6. doi: 10.1210/endo-126-2-971.
11	A study of human growth hormone and insulin gene regions in relation to metabolic control of non-insulin-dependent diabetes mellitus.Metabolism. 2000 Apr;49(4):424-6. doi: 10.1016/s0026-0495(00)81092-6.
12	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
13	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.
14	Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.