Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9RMLBJ)

• DOT Name: Transmembrane protein 107 (TMEM107)
• Gene Name: TMEM107
• Related Disease:
  Meckel syndrome 13
  Orofaciodigital syndrome 16
  Polydactyly
  Ciliopathy
  Meckel syndrome, type 1
  Orofaciodigital syndrome
  Meckel syndrome
  Joubert syndrome
  Orofaciodigital syndrome I
• UniProt ID: TM107_HUMAN
• Pfam ID: PF14995
• Sequence:
  MGRVSGLVPSRFLTLLAHLVVVITLFWSRDSNIQACLPLTFTPEEYDKQDIQLVAALSVT
  LGLFAVELAGFLSGVSMFNSTQSLISIGAHCSASVALSFFIFERWECTTYWYIFVFCSAL
  PAVTEMALFVTVFGLKKKPF
• Function: Plays a role in cilia formation and embryonic patterning. Requires for normal Sonic hedgehog (Shh) signaling in the neural tube and acts in combination with GLI2 and GLI3 to pattern ventral and intermediate neuronal cell types. During ciliogenesis regulates the ciliary transition zone localization of some MKS complex proteins.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meckel syndrome 13	DISXYQQG	Strong	Autosomal recessive	[1]
Orofaciodigital syndrome 16	DISJ9W3J	Strong	Biomarker	[2]
Polydactyly	DIS25BMZ	Strong	Genetic Variation	[2]
Ciliopathy	DIS10G4I	Moderate	Autosomal recessive	[3]
Meckel syndrome, type 1	DIS4YWZU	moderate	Biomarker	[4]
Orofaciodigital syndrome	DISSB296	moderate	Genetic Variation	[5]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[6]
Joubert syndrome	DIS7P5CO	Limited	Genetic Variation	[5]
Orofaciodigital syndrome I	DIST27XL	Limited	Genetic Variation	[5]

15 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 Transmembrane protein 107 (TMEM107).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 107 (TMEM107).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 107 (TMEM107).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 107 (TMEM107).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transmembrane protein 107 (TMEM107).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transmembrane protein 107 (TMEM107).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane protein 107 (TMEM107).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transmembrane protein 107 (TMEM107).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein 107 (TMEM107).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 107 (TMEM107).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transmembrane protein 107 (TMEM107).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane protein 107 (TMEM107).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 107 (TMEM107).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transmembrane protein 107 (TMEM107).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transmembrane protein 107 (TMEM107).	[20]

References

• [1] Forward genetics uncovers Transmembrane protein 107 as a novel factor required for ciliogenesis and Sonic hedgehog signaling. Dev Biol. 2012 Aug 15;368(2):382-92. doi: 10.1016/j.ydbio.2012.06.008. Epub 2012 Jun 12.
• [2] TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome.Hum Mutat. 2016 Feb;37(2):155-9. doi: 10.1002/humu.22925. Epub 2015 Nov 23.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubertsyndrome.Nat Cell Biol. 2016 Jan;18(1):122-31. doi: 10.1038/ncb3273. Epub 2015 Nov 23.
• [5] Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development.J Dent Res. 2018 Jan;97(1):108-117. doi: 10.1177/0022034517732538. Epub 2017 Sep 27.
• [6] Identification of a novel MKS locus defined by TMEM107 mutation. Hum Mol Genet. 2015 Sep 15;24(18):5211-8. doi: 10.1093/hmg/ddv242. Epub 2015 Jun 29.
• [7] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.