Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTA14N)

• DOT Name: Protein FAM177A1 (FAM177A1)
• Gene Name: FAM177A1
• Related Disease:
  Atopic dermatitis
  Juvenile idiopathic arthritis
  Bipolar disorder
  Schizophrenia
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: F177A_HUMAN
• Pfam ID: PF14774
• Sequence:
  MDQEPVGGVERGEAVAASGAAAAAAFGESAGQMSNERGFENVELGVIGKKKKVPRRVIHF
  VSGETMEEYSTDEDEVDGLEKKDVLPTVDPTKLTWGPYLWFYMLRAATSTLSVCDFLGEK
  IASVLGISTPKYQYAIDEYYRMKKEEEEEEEENRMSEEAEKQYQQNKLQTDSIVQTDQPE
  TVISSSFVNVNFEMEGDSEVIMESKQNPVSVPP

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[2]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[3]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[3]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[4]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[4]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[4]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[4]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[4]

5 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 Protein FAM177A1 (FAM177A1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein FAM177A1 (FAM177A1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FAM177A1 (FAM177A1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM177A1 (FAM177A1).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein FAM177A1 (FAM177A1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein FAM177A1 (FAM177A1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein FAM177A1 (FAM177A1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein FAM177A1 (FAM177A1).	[10]

References

• [1] Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.Nat Genet. 2015 Dec;47(12):1449-1456. doi: 10.1038/ng.3424. Epub 2015 Oct 19.
• [2] Identification of a novel candidate locus for juvenile idiopathic arthritis at 14q13.2 in the Latvian population by association analysis with microsatellite markers.DNA Cell Biol. 2010 Sep;29(9):543-51. doi: 10.1089/dna.2009.0970.
• [3] Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.JAMA Psychiatry. 2018 Jan 1;75(1):65-74. doi: 10.1001/jamapsychiatry.2017.3433.
• [4] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.