Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4H7ZZ)

• DOT Name: Protein HGH1 homolog (HGH1)
• Gene Name: HGH1
• Related Disease:
  Cystic fibrosis
  Pituitary dwarfism
  Hypoglycemia
• UniProt ID: HGH1_HUMAN
• Pfam ID: PF04063 ; PF04064
• Sequence:
  MGEAGAGAGASGGPEASPEAEVVKLLPFLAPGARADLQAAAVRHVLALTGCGPGRALLAG
  QAALLQALMELAPASAPARDAARALVNLAADPGLHETLLAADPGLPARLMGRALDPQWPW
  AEEAAAALANLSREPAPCAALMAALAAAEPADSGLERLVRALCTPGYNARAPLHYLAPLL
  SNLSQRPAARAFLLDPDRCVVQRLLPLTQYPDSSVRRGGVVGTLRNCCFEHRHHEWLLGP
  EVDILPFLLLPLAGPEDFSEEEMERLPVDLQYLPPDKQREPDADIRKMLVEAIMLLTATA
  PGRQQVRDQGAYLILRELHSWEPEPDVRTACEKLIQVLIGDEPERGMENLLEVQVPEDVE
  QQLQQLDCREQEQLERELAPEPWVERATPT

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[1]
Pituitary dwarfism	DISI019B	Strong	Genetic Variation	[2]
Hypoglycemia	DISRCKR7	moderate	Genetic Variation	[3]

1 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 Protein HGH1 homolog (HGH1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein HGH1 homolog (HGH1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein HGH1 homolog (HGH1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein HGH1 homolog (HGH1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein HGH1 homolog (HGH1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein HGH1 homolog (HGH1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein HGH1 homolog (HGH1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein HGH1 homolog (HGH1).	[11]

References

• [1] Short stature in a patient with cystic fibrosis caused by a 6.7-kb human growth hormone gene deletion.Horm Res. 1991;36(1-2):4-8. doi: 10.1159/000182097.
• [2] The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions.Clin Endocrinol (Oxf). 1992 Jul;37(1):89-95. doi: 10.1111/j.1365-2265.1992.tb02288.x.
• [3] Analyses of insulin-potentiating fragments of human growth hormone by computative simulation; essential unit for insulin-involved biological responses.Bioorg Med Chem. 2000 Jul;8(7):1733-40. doi: 10.1016/s0968-0896(00)00105-x.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.