Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9CID5R)

• DOT Name: Formin-1 (FMN1)
• Synonyms: Limb deformity protein homolog
• Gene Name: FMN1
• Related Disease:
  Congenital radioulnar synostosis
  Cutaneous melanoma
  Acute myocardial infarction
  Bladder cancer
  Breast cancer
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Familial adenomatous polyposis
  Mitochondrial complex I deficiency
  Polyposis
  Polyposis syndrome, hereditary mixed, 1
  Trichomoniasis
  Malaria
• UniProt ID: FMN1_HUMAN
• Pfam ID: PF02181
• Sequence:
  MEGTHCTLQLHKPITELCYISFCLPKGEVRGFSYKGTVTLDRSNKGFHNCYQVREESDII
  SLSQEPDEHPGDIFFKQTPTKDILTELYKLTTERERLLTNLLSSDHILGITMGNQEGKLQ
  ELSVSLAPEDDCFQSAGDWQGELPVGPLNKRSTHGNKKPRRSSGRRESFGALPQKRTKRK
  GRGGRESAPLMGKDKICSSHSLPLSRTRPNLWVLEEKGNLLPNGALACSLQRRESCPPDI
  PKTPDTDLGFGSFETAFKDTGLGREVLPPDCSSTEAGGDGIRRPPSGLEHQQTGLSESHQ
  DPEKHPEAEKDEMEKPAKRTCKQKPVSKVVAKVQDLSSQVQRVVKTHSKGKETIAIRPAA
  HAEFVPKADLLTLPGAEAGAHGSRRQGKERQGDRSSQSPAGETASISSVSASAEGAVNKV
  PLKVIESEKLDEAPEGKRLGFPVHTSVPHTRPETRNKRRAGLPLGGHKSLFLDLPHKVGP
  DSSQPRGDKKKPSPPAPAALGKVFNNSASQSSTHKQTSPVPSPLSPRLPSPQQHHRILRL
  PALPGEREAALNDSPCRKSRVFSGCVSADTLEPPSSAKVTETKGASPAFLRAGQPRLVPG
  ETLEKSLGPGKTTAEPQHQSPPGISSEGFPWDGFNEQTPKDLPNRDGGAWVLGYRAGPAC
  PFLLHEEREKSNRSELYLDLHPDHSLTEQDDRTPGRLQAVWPPPKTKDTEEKVGLKYTEA
  EYQAAILHLKREHKEEIENLQAQFELRAFHIRGEHAMITARLEETIENLKHELEHRWRGG
  CEERKDVCISTDDDCPPKTFRNVCVQTDRETFLKPCESESKTTRSNQLVPKKLNISSLSQ
  LSPPNDHKDIHAALQPMEGMASNQQKALPPPPASIPPPPPLPSGLGSLSPAPPMPPVSAG
  PPLPPPPPPPPPLPPPSSAGPPPPPPPPPLPNSPAPPNPGGPPPAPPPPGLAPPPPPGLF
  FGLGSSSSQCPRKPAIEPSCPMKPLYWTRIQISDRSQNATPTLWDSLEEPDIRDPSEFEY
  LFSKDTTQQKKKPLSETYEKKNKVKKIIKLLDGKRSQTVGILISSLHLEMKDIQQAIFNV
  DDSVVDLETLAALYENRAQEDELVKIRKYYETSKEEELKLLDKPEQFLHELAQIPNFAER
  AQCIIFRSVFSEGITSLHRKVEIITRASKDLLHVKSVKDILALILAFGNYMNGGNRTRGQ
  ADGYSLEILPKLKDVKSRDNGINLVDYVVKYYLRYYDQEAGTEKSVFPLPEPQDFFLASQ
  VKFEDLIKDLRKLKRQLEASEKQMVVVCKESPKEYLQPFKDKLEEFFQKAKKEHKMEESH
  LENAQKSFETTVRYFGMKPKSGEKEITPSYVFMVWYEFCSDFKTIWKRESKNISKERLKM
  AQESVSKLTSEKKVETKKINPTASLKERLRQKEASVTTN
• Function: Plays a role in the formation of adherens junction and the polymerization of linear actin cables.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital radioulnar synostosis	DISF96QX	Definitive	Genetic Variation	[1]
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[2]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[6]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[6]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[7]
Mitochondrial complex I deficiency	DIS13M7V	Strong	Genetic Variation	[8]
Polyposis	DISZSPOK	Strong	Biomarker	[7]
Polyposis syndrome, hereditary mixed, 1	DISG6RBU	Strong	Genetic Variation	[9]
Trichomoniasis	DIS9HBNL	Strong	Biomarker	[10]
Malaria	DISQ9Y50	Limited	Biomarker	[11]

10 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 Formin-1 (FMN1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Formin-1 (FMN1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Formin-1 (FMN1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Formin-1 (FMN1).	[16]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Formin-1 (FMN1).	[17]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Formin-1 (FMN1).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Formin-1 (FMN1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Formin-1 (FMN1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Formin-1 (FMN1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Formin-1 (FMN1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Formin-1 (FMN1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Formin-1 (FMN1).	[19]

References

• [1] Genomic rearrangements of the GREM1-FMN1 locus cause oligosyndactyly, radio-ulnar synostosis, hearing loss, renal defects syndrome and Cenani--Lenz-like non-syndromic oligosyndactyly.J Med Genet. 2010 Aug;47(8):569-74. doi: 10.1136/jmg.2009.073833. Epub 2010 Jul 7.
• [2] Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.Nat Commun. 2018 Nov 14;9(1):4774. doi: 10.1038/s41467-018-06649-5.
• [3] CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction.J Thromb Thrombolysis. 2013 Oct;36(3):332-40. doi: 10.1007/s11239-012-0841-4.
• [4] Genome-wide interaction study of smoking and bladder cancer risk.Carcinogenesis. 2014 Aug;35(8):1737-44. doi: 10.1093/carcin/bgu064. Epub 2014 Mar 24.
• [5] A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.Nat Genet. 2010 Oct;42(10):885-92. doi: 10.1038/ng.669. Epub 2010 Sep 19.
• [6] Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
• [7] Cenani-Lenz syndrome and other related syndactyly disorders due to variants in LRP4, GREM1/FMN1, and APC: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways.Am J Med Genet A. 2019 Feb;179(2):266-279. doi: 10.1002/ajmg.a.60694. Epub 2018 Dec 20.
• [8] Genetic diversity of NDUFV1-dependent mitochondrial complex I deficiency.Eur J Hum Genet. 2018 Nov;26(11):1582-1587. doi: 10.1038/s41431-018-0209-0. Epub 2018 Jul 5.
• [9] Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk.Nat Genet. 2008 Jan;40(1):26-8. doi: 10.1038/ng.2007.41. Epub 2007 Dec 16.
• [10] Transcriptomics Indicates Active and Passive Metronidazole Resistance Mechanisms in Three Seminal Giardia Lines.Front Microbiol. 2017 Mar 17;8:398. doi: 10.3389/fmicb.2017.00398. eCollection 2017.
• [11] Deficiency of two red-cell flavin enzymes in a population in Sardinia: was glutathione reductase deficiency specifically selected for by malaria?.Am J Hum Genet. 1995 Sep;57(3):674-81.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [18] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [19] 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.
• [20] 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.
• [21] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.