Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLP5QEJ)

• DOT Name: Interferon-induced transmembrane protein 5 (IFITM5)
• Synonyms: Bone-restricted interferon-induced transmembrane protein-like protein; BRIL; Dispanin subfamily A member 1; DSPA1
• Gene Name: IFITM5
• Related Disease:
  Osteogenesis imperfecta type 5
  Osteogenesis imperfecta
  Osteogenesis imperfecta type 4
  Osteogenesis imperfecta type 6
  Osteoporosis
  Bone osteosarcoma
  Neoplasm
  Osteosarcoma
• UniProt ID: IFM5_HUMAN
• Pfam ID: PF04505
• Sequence:
  MDTAYPREDTRAPTPSKAGAHTALTLGAPHPPPRDHLIWSVFSTLYLNLCCLGFLALAYS
  IKARDQKVVGDLEAARRFGSKAKCYNILAAMWTLVPPLLLLGLVVTGALHLARLAKDSAA
  FFSTKFDDADYD
• Function: Required for normal bone mineralization.
• Tissue Specificity: Detected in osteoblasts and fibroblasts (at protein level) . Detected in bone .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta type 5	DISXSBGZ	Definitive	Autosomal dominant	[1]
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[2]
Osteogenesis imperfecta type 4	DIS8S46L	Strong	Genetic Variation	[3]
Osteogenesis imperfecta type 6	DIS0ZNUU	Strong	Genetic Variation	[4]
Osteoporosis	DISF2JE0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[6]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[6]

2 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 Interferon-induced transmembrane protein 5 (IFITM5).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon-induced transmembrane protein 5 (IFITM5).	[8]

References

• [1] A single recurrent mutation in the 5'-UTR of IFITM5 causes osteogenesis imperfecta type V. Am J Hum Genet. 2012 Aug 10;91(2):343-8. doi: 10.1016/j.ajhg.2012.06.005. Epub 2012 Aug 2.
• [2] Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V.Eur J Med Genet. 2019 Dec;62(12):103606. doi: 10.1016/j.ejmg.2018.12.011. Epub 2018 Dec 26.
• [3] Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM5 gene.J Bone Miner Res. 2013 Nov;28(11):2333-7. doi: 10.1002/jbmr.1983.
• [4] A novel IFITM5 mutation in severe atypical osteogenesis imperfecta type VI impairs osteoblast production of pigment epithelium-derived factor.J Bone Miner Res. 2014 Jun;29(6):1402-11. doi: 10.1002/jbmr.2173.
• [5] Bruck syndrome 2 variant lacking congenital contractures and involving a novel compound heterozygous PLOD2 mutation.Bone. 2020 Jan;130:115047. doi: 10.1016/j.bone.2019.115047. Epub 2019 Aug 28.
• [6] Effects of the overexpression of IFITM5 and IFITM5 c.-14C>T mutation on human osteosarcoma cells.Oncol Lett. 2017 Jan;13(1):111-118. doi: 10.3892/ol.2016.5426. Epub 2016 Nov 23.
• [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] 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.