Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0HFEIC)

• DOT Name: Transmembrane protein 119 (TMEM119)
• Synonyms: Osteoblast induction factor; OBIF
• Gene Name: TMEM119
• Related Disease:
  Alzheimer disease
  Cerebral infarction
  Multiple sclerosis
  Bone osteosarcoma
  Myotonic dystrophy type 1
  Neoplasm
  Osteosarcoma
  Type-1/2 diabetes
• UniProt ID: TM119_HUMAN
• Pfam ID: PF15724
• Sequence:
  MVSAAAPSLLILLLLLLGSVPATDARSVPLKATFLEDVAGSGEAEGSSASSPSLPPPWTP
  ALSPTSMGPQPITLGGPSPPTNFLDGIVDFFRQYVMLIAVVGSLAFLLMFIVCAAVITRQ
  KQKASAYYPSSFPKKKYVDQSDRAGGPRAFSEVPDRAPDSRPEEALDSSRQLQADILAAT
  QNLKSPTRAALGGGDGARMVEGRGAEEEEKGSQEGDQEVQGHGVPVETPEAQEEPCSGVL
  EGAVVAGEGQGELEGSLLLAQEAQGPVGPPESPCACSSVHPSV
• Function: Plays an important role in bone formation and normal bone mineralization. Promotes the differentiation of myoblasts into osteoblasts. May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway. Up-regulates the expression of ATF4, a transcription factor which plays a central role in osteoblast differentiation. Essential for normal spermatogenesis and late testicular differentiation.
• Tissue Specificity: Expressed in brain microglia (at protein level) . Detected in urine (at protein level) . Elevated expression levels seen in the brain of patients with Alzheimer disease . Expressed by osteoblast-like cells in bone tissues and follicular dendritic cells in lymphoid tissues .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[2]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[4]
Myotonic dystrophy type 1	DISJC0OX	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[5]

9 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 Transmembrane protein 119 (TMEM119).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 119 (TMEM119).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 119 (TMEM119).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transmembrane protein 119 (TMEM119).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane protein 119 (TMEM119).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transmembrane protein 119 (TMEM119).	[12]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Transmembrane protein 119 (TMEM119).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 119 (TMEM119).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 119 (TMEM119).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Transmembrane protein 119 (TMEM119).	[7]

References

• [1] Distinct microglia profile in Creutzfeldt-Jakob disease and Alzheimer's disease is independent of disease kinetics.Neuropathology. 2018 Dec;38(6):591-600. doi: 10.1111/neup.12517. Epub 2018 Oct 15.
• [2] TMEM119 marks a subset of microglia in the human brain.Neuropathology. 2016 Feb;36(1):39-49. doi: 10.1111/neup.12235. Epub 2015 Aug 6.
• [3] Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes.Nat Commun. 2019 Mar 13;10(1):1139. doi: 10.1038/s41467-019-08976-7.
• [4] Upregulation and biological function of transmembrane protein 119 in osteosarcoma.Exp Mol Med. 2017 May 12;49(5):e329. doi: 10.1038/emm.2017.41.
• [5] Effects of spinal non-viral interleukin-10 gene therapy formulated with d-mannose in neuropathic interleukin-10 deficient mice: Behavioral characterization, mRNA and protein analysis in pain relevant tissues.Brain Behav Immun. 2018 Mar;69:91-112. doi: 10.1016/j.bbi.2017.11.004. Epub 2017 Nov 4.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] 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.