Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SUTZR)

• DOT Name: Inhibin beta C chain (INHBC)
• Synonyms: Activin beta-C chain
• Gene Name: INHBC
• Related Disease:
  Chronic renal failure
  Nephropathy
  Adenoma
  Diabetic kidney disease
  Endometrium adenocarcinoma
  Gout
  Non-small-cell lung cancer
• UniProt ID: INHBC_HUMAN
• Pfam ID: PF00019
• Sequence:
  MTSSLLLAFLLLAPTTVATPRAGGQCPACGGPTLELESQRELLLDLAKRSILDKLHLTQR
  PTLNRPVSRAALRTALQHLHGVPQGALLEDNREQECEIISFAETGLSTINQTRLDFHFSS
  DRTAGDREVQQASLMFFVQLPSNTTWTLKVRVLVLGPHNTNLTLATQYLLEVDASGWHQL
  PLGPEAQAACSQGHLTLELVLEGQVAQSSVILGGAAHRPFVAARVRVGGKHQIHRRGIDC
  QGGSRMCCRQEFFVDFREIGWHDWIIQPEGYAMNFCIGQCPLHIAGMPGIAASFHTAVLN
  LLKANTAAGTTGGGSCCVPTARRPLSLLYYDRDSNIVKTDIPDMVVEACGCS
• Function: Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
• Tissue Specificity: Expressed in benign prostatic hyperplasia.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Glycoprotein hormones (R-HSA-209822)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[4]
Endometrium adenocarcinoma	DISY6744	Strong	Biomarker	[5]
Gout	DISHC0U7	Strong	Genetic Variation	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Inhibin beta C chain (INHBC).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inhibin beta C chain (INHBC).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inhibin beta C chain (INHBC).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Inhibin beta C chain (INHBC).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inhibin beta C chain (INHBC).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Inhibin beta C chain (INHBC).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Inhibin beta C chain (INHBC).	[14]

References

• [1] Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.Mol Genet Genomics. 2018 Apr;293(2):371-379. doi: 10.1007/s00438-017-1394-1. Epub 2017 Nov 9.
• [2] Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.Rheumatol Int. 2016 Feb;36(2):263-70. doi: 10.1007/s00296-015-3364-4. Epub 2015 Oct 1.
• [3] The CXCR4 antagonist AMD3100 suppresses hypoxia-mediated growth hormone production in GH3 rat pituitary adenoma cells.J Neurooncol. 2010 Oct;100(1):51-64. doi: 10.1007/s11060-010-0152-6. Epub 2010 Mar 23.
• [4] Key Genes and Signaling Pathways Contribute to the Pathogensis of Diabetic Nephropathy.Iran J Kidney Dis. 2019 Mar;13(2):87-97.
• [5] The inhibin-C subunit is down-regulated, while inhibin-E is up-regulated by interferon-1a in Ishikawa carcinoma cell line.Arch Gynecol Obstet. 2013 Oct;288(4):883-8. doi: 10.1007/s00404-013-2848-2. Epub 2013 Apr 12.
• [6] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [7] SNPs in the TGF- signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.PLoS One. 2012;7(12):e51713. doi: 10.1371/journal.pone.0051713. Epub 2012 Dec 17.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.