Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7V1MLD)

• DOT Name: Protein C10 (C12ORF57)
• Gene Name: C12ORF57
• Related Disease:
  Coloboma
  Microphthalmia, isolated, with coloboma
  Temtamy syndrome
  Intellectual disability
• UniProt ID: C10_HUMAN
• Pfam ID: PF14974
• Sequence:
  MASASTQPAALSAEQAKVVLAEVIQAFSAPENAVRMDEARDNACNDMGKMLQFVLPVATQ
  IQQEVIKAYGFSCDGEGVLKFARLVKSYEAQDPEIASLSGKLKALFLPPMTLPPHGPAAG
  GSVAAS
• Function: In brain, may be required for corpus callosum development.
• Tissue Specificity: Ubiquitously expressed, with higher expression in lung and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coloboma	DISP39N5	Strong	Genetic Variation	[1]
Microphthalmia, isolated, with coloboma	DISLSEUJ	Strong	Genetic Variation	[2]
Temtamy syndrome	DISNLPC3	Strong	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein C10 (C12ORF57).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein C10 (C12ORF57).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein C10 (C12ORF57).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein C10 (C12ORF57).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein C10 (C12ORF57).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein C10 (C12ORF57).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein C10 (C12ORF57).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein C10 (C12ORF57).	[12]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols increases the expression of Protein C10 (C12ORF57).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein C10 (C12ORF57).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein C10 (C12ORF57).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein C10 (C12ORF57).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein C10 (C12ORF57).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein C10 (C12ORF57).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein C10 (C12ORF57).	[19]

References

• [1] The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur J Med Genet. 2014 Aug;57(8):369-80. doi: 10.1016/j.ejmg.2014.05.002. Epub 2014 May 22.
• [2] Mutations in c12orf57 cause a syndromic form of colobomatous microphthalmia. Am J Hum Genet. 2013 Mar 7;92(3):387-91. doi: 10.1016/j.ajhg.2013.01.008. Epub 2013 Feb 28.
• [3] Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. Am J Hum Genet. 2013 Mar 7;92(3):392-400. doi: 10.1016/j.ajhg.2013.02.004. Epub 2013 Feb 28.
• [4] Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities.Am J Med Genet A. 2018 Mar;176(3):715-721. doi: 10.1002/ajmg.a.38615. Epub 2018 Jan 31.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [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] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.