Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9JF3JQ)

• DOT Name: Protein FAM167A (FAM167A)
• Gene Name: FAM167A
• Related Disease:
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Allergic rhinitis
  Asthma
  Autoimmune disease
  Idiopathic inflammatory myopathy
  Lupus
  Systemic sclerosis
  Lupus nephritis
  Cutaneous mastocytosis
  Dermatomyositis
  Multiple sclerosis
  Neoplasm of esophagus
  Polymyositis
  Rheumatic disorder
  Rheumatoid arthritis
  Sjogren syndrome
  Systemic lupus erythematosus
  Type-1 diabetes
• UniProt ID: F167A_HUMAN
• Pfam ID: PF11652
• Sequence:
  MSVPQIHVEEVGAEEGAGAAAPPDDHLRSLKALTEKLRLETRRPSYLEWQARLEEHTWPF
  PRPAAEPQASLEEGERGGQEPLLPLREAGQHPPSARSASQGARPLSTGKLEGFQSIDEAI
  AWLRKELTEMRLQDQQLARQLMRLRGDINKLKIEHTCRLHRRMLNDATYELEERDELADL
  FCDSPLASSFSLSTPLKLIGVTKMNINSRRFSLC
• Tissue Specificity: Expressed in skin, including primary keratinocytes, spleen, kidney, leukocytes, testis, lung, small intestine and prostate.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peeling skin syndrome 1	DIS35574	Definitive	Genetic Variation	[1]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Genetic Variation	[1]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[2]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Genetic Variation	[4]
Lupus	DISOKJWA	Strong	Genetic Variation	[5]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[6]
Lupus nephritis	DISCVGPZ	moderate	Genetic Variation	[7]
Cutaneous mastocytosis	DISLBZEF	Limited	Genetic Variation	[8]
Dermatomyositis	DIS50C5O	Limited	Genetic Variation	[4]
Multiple sclerosis	DISB2WZI	Limited	Genetic Variation	[9]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[10]
Polymyositis	DIS5DHFP	Limited	Genetic Variation	[4]
Rheumatic disorder	DIS77ACK	Limited	Genetic Variation	[11]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[9]
Sjogren syndrome	DISUBX7H	Limited	Genetic Variation	[11]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[5]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[9]

12 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 FAM167A (FAM167A).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FAM167A (FAM167A).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM167A (FAM167A).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM167A (FAM167A).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein FAM167A (FAM167A).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein FAM167A (FAM167A).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein FAM167A (FAM167A).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein FAM167A (FAM167A).	[15]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Protein FAM167A (FAM167A).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein FAM167A (FAM167A).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein FAM167A (FAM167A).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM167A (FAM167A).	[22]

References

• [1] Polymorphisms in the FAM167A-BLK, but not BANK1, are associated with primary Sjgren's syndrome in a Han Chinese population.Clin Exp Rheumatol. 2013 Sep-Oct;31(5):704-10. Epub 2013 Jul 30.
• [2] Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population.J Asthma. 2016 Aug;53(6):567-75. doi: 10.3109/02770903.2015.1108437. Epub 2016 Apr 18.
• [3] Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseases: A Meta-Analysis.Immunol Invest. 2016 May;45(4):336-48. doi: 10.3109/08820139.2016.1157812. Epub 2016 Apr 22.
• [4] Single nucleotide polymorphisms in the FAM167A-BLK gene are associated with polymyositis/dermatomyositis in the Han Chinese population.Immunol Res. 2015 Jun;62(2):153-62. doi: 10.1007/s12026-015-8646-0.
• [5] Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription.Am J Hum Genet. 2014 Apr 3;94(4):586-98. doi: 10.1016/j.ajhg.2014.03.008.
• [6] Possible single-nucleotide polymorphism loci associated with systemic sclerosis susceptibility: a genetic association study in a Chinese Han population.PLoS One. 2014 Dec 3;9(12):e113197. doi: 10.1371/journal.pone.0113197. eCollection 2014.
• [7] Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.PLoS One. 2012;7(9):e45356. doi: 10.1371/journal.pone.0045356. Epub 2012 Sep 26.
• [8] Identification of a locus for maturity-onset diabetes of the young on chromosome 8p23.Diabetes. 2004 May;53(5):1375-84. doi: 10.2337/diabetes.53.5.1375.
• [9] Evaluation of 19 autoimmune disease-associated loci with rheumatoid arthritis in a Colombian population: evidence for replication and gene-gene interaction.J Rheumatol. 2011 Sep;38(9):1866-70. doi: 10.3899/jrheum.110199. Epub 2011 Jul 15.
• [10] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [11] The rheumatic disease-associated FAM167A-BLK locus encodes DIORA-1, a novel disordered protein expressed highly in bronchial epithelium and alveolar macrophages.Clin Exp Immunol. 2018 Aug;193(2):167-177. doi: 10.1111/cei.13138. Epub 2018 May 16.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [15] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [16] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [17] 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.
• [18] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [19] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [20] 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.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.