Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBYON4H)

• DOT Name: BMP-binding endothelial regulator protein (BMPER)
• Synonyms: Bone morphogenetic protein-binding endothelial cell precursor-derived regulator; Protein crossveinless-2; hCV2
• Gene Name: BMPER
• Related Disease:
  Diaphanospondylodysostosis
  Liver cirrhosis
  Alzheimer disease
  Anemia
  Disorder of sexual differentiation
  Hantavirus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  High blood pressure
  Opioid dependence
  Von willebrand disease
  Ischio-vertebral syndrome
  Fatty liver disease
• UniProt ID: BMPER_HUMAN
• Pfam ID: PF08742 ; PF01826 ; PF00093 ; PF00094
• Sequence:
  MLWFSGVGALAERYCRRSPGITCCVLLLLNCSGVPMSLASSFLTGSVAKCENEGEVLQIP
  FITDNPCIMCVCLNKEVTCKREKCPVLSRDCALAIKQRGACCEQCKGCTYEGNTYNSSFK
  WQSPAEPCVLRQCQEGVVTESGVRCVVHCKNPLEHLGMCCPTCPGCVFEGVQYQEGEEFQ
  PEGSKCTKCSCTGGRTQCVREVCPILSCPQHLSHIPPGQCCPKCLGQRKVFDLPFGSCLF
  RSDVYDNGSSFLYDNCTACTCRDSTVVCKRKCSHPGGCDQGQEGCCEECLLRVPPEDIKV
  CKFGNKIFQDGEMWSSINCTICACVKGRTECRNKQCIPISSCPQGKILNRKGCCPICTEK
  PGVCTVFGDPHYNTFDGRTFNFQGTCQYVLTKDCSSPASPFQVLVKNDARRTRSFSWTKS
  VELVLGESRVSLQQHLTVRWNGSRIALPCRAPHFHIDLDGYLLKVTTKAGLEISWDGDSF
  VEVMAAPHLKGKLCGLCGNYNGHKRDDLIGGDGNFKFDVDDFAESWRVESNEFCNRPQRK
  PVPELCQGTVKVKLRAHRECQKLKSWEFQTCHSTVDYATFYRSCVTDMCECPVHKNCYCE
  SFLAYTRACQREGIKVHWEPQQNCAATQCKHGAVYDTCGPGCIKTCDNWNEIGPCNKPCV
  AGCHCPANLVLHKGRCIKPVLCPQR
• Function: Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes.
• Tissue Specificity: Highly expressed in lung, and brain and also in primary chondrocytes.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diaphanospondylodysostosis	DIS6F2GV	Definitive	Autosomal recessive	[1]
Liver cirrhosis	DIS4G1GX	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Anemia	DISTVL0C	Strong	Genetic Variation	[4]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[5]
Hantavirus infection	DISZFTMH	Strong	Altered Expression	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
High blood pressure	DISY2OHH	Strong	Biomarker	[9]
Opioid dependence	DIS6WEHK	Strong	Biomarker	[10]
Von willebrand disease	DIS3TZCH	Strong	Genetic Variation	[11]
Ischio-vertebral syndrome	DISEED6L	Supportive	Autosomal recessive	[12]
Fatty liver disease	DIS485QZ	Limited	Biomarker	[9]

12 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 BMP-binding endothelial regulator protein (BMPER).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BMP-binding endothelial regulator protein (BMPER).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BMP-binding endothelial regulator protein (BMPER).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of BMP-binding endothelial regulator protein (BMPER).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of BMP-binding endothelial regulator protein (BMPER).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of BMP-binding endothelial regulator protein (BMPER).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of BMP-binding endothelial regulator protein (BMPER).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of BMP-binding endothelial regulator protein (BMPER).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of BMP-binding endothelial regulator protein (BMPER).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BMP-binding endothelial regulator protein (BMPER).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BMP-binding endothelial regulator protein (BMPER).	[21]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of BMP-binding endothelial regulator protein (BMPER).	[22]

References

• [1] BMPER mutation in diaphanospondylodysostosis identified by ancestral autozygosity mapping and targeted high-throughput sequencing. Am J Hum Genet. 2010 Oct 8;87(4):532-7. doi: 10.1016/j.ajhg.2010.08.015.
• [2] Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis.Hepatology. 1997 Jan;25(1):211-5. doi: 10.1053/jhep.1997.v25.pm0008985292.
• [3] ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology.Acta Neuropathol. 2014;127(6):825-43. doi: 10.1007/s00401-014-1282-2. Epub 2014 Apr 27.
• [4] Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR.Hepatology. 2011 Feb;53(2):389-95. doi: 10.1002/hep.24068. Epub 2011 Jan 10.
• [5] Diaphanospondylodysostosis: Refining the prenatal diagnosis of a rare skeletal disorder.Eur J Med Genet. 2019 Mar;62(3):167-171. doi: 10.1016/j.ejmg.2018.07.004. Epub 2018 Jul 10.
• [6] Cyclooxygenase-2 promotes pulmonary intravascular macrophage accumulation by exacerbating BMP signaling in rat experimental hepatopulmonary syndrome.Biochem Pharmacol. 2017 Aug 15;138:205-215. doi: 10.1016/j.bcp.2017.06.117. Epub 2017 Jun 19.
• [7] Synthetic Antibody Binding to a Preorganized RNA Domain of Hepatitis C Virus Internal Ribosome Entry Site Inhibits Translation.ACS Chem Biol. 2020 Jan 17;15(1):205-216. doi: 10.1021/acschembio.9b00785. Epub 2019 Dec 10.
• [8] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [9] Do differences exist between chronic hepatitis C genotypes 2 and 3?.Rev Soc Bras Med Trop. 2014 Mar-Apr;47(2):143-8. doi: 10.1590/0037-8682-0269-2013.
• [10] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [11] Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4) antagonist identified in pituitary cells.J Biol Chem. 2017 Sep 15;292(37):15352-15368. doi: 10.1074/jbc.M116.736207. Epub 2017 Jul 26.
• [12] Extending the phenotype of BMPER-related skeletal dysplasias to ischiospinal dysostosis. Orphanet J Rare Dis. 2016 Jan 4;11:1. doi: 10.1186/s13023-015-0380-0.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] 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.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [21] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [22] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.