Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ11849)

• DOT Name: FERM domain-containing protein 7 (FRMD7)
• Gene Name: FRMD7
• Related Disease:
  Achromatopsia
  Albinism
  Congenital fibrosis of extraocular muscles
  Cystic fibrosis
  Influenza
  Neuroblastoma
  Nystagmus 1, congenital, X-linked
  Ocular albinism
  Pathologic nystagmus
  Acquired nystagmus
• UniProt ID: FRMD7_HUMAN
• Pfam ID: PF08736 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MLHLKVQFLDDSQKIFVVDQKSSGKALFNLSCSHLNLAEKEYFGLEFCSHSGNNVWLELL
  KPITKQVKNPKEIVFKFMVKFFPVDPGHLREELTRYLFTLQIKKDLALGRLPCSDNCTAL
  MVSHILQSELGDFHEETDRKHLAQTRYLPNQDCLEGKIMHFHQKHIGRSPAESDILLLDI
  ARKLDMYGIRPHPASDGEGMQIHLAVAHMGVLVLRGNTKINTFNWAKIRKLSFKRKHFLI
  KLHANILVLCKDTLEFTMASRDACKAFWKTCVEYHAFFRLSEEPKSKPKTLLCSKGSSFR
  YSGRTQRQLLEYGRKGRLKSLPFERKHYPSQYHERQCRSSPDLLSDVSKQVEDLRLAYGG
  GYYQNVNGVHASEPVLESRRRNSALEVTFATELEHSKPEADPTLLHQSQSSSSFPFIYMD
  PVFNTEPNPNPDPRDIFSERSSLSSFQTSCKFSGNHMSIYSGLTSKVRPAKQLTYTDVPY
  IPCTGQQVGIMPPQVFFYVDKPPQVPRWSPIRAEERTSPHSYVEPTAMKPAERSPRNIRM
  KSFQQDLQVLQEAIARTSGRSNINVGLEEEDPNLEDAFVCNIQEQTPKRSQSQSDMKTIR
  FPFGSEFRPLGPCPALSHKADLFTDMFAEQELPAVLMDQSTAERYVASESSDSESEILKP
  DYYALYGKEIRSPMARIRLSSGSLQLDEEDEDAYFNTPTAEDRTSLKPCNYFLA
• Function: Plays a role in neurite development, may be through the activation of the GTPase RAC1. Plays a role in the control of eye movement and gaze stability.
• Tissue Specificity: Expressed in liver, kidney, pancreas and at low levels in brain and heart. Expressed in embryonic brain and developing neural retina.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achromatopsia	DISKL51I	Strong	Genetic Variation	[1]
Albinism	DIS5D82I	Strong	Biomarker	[2]
Congenital fibrosis of extraocular muscles	DISE84PU	Strong	Genetic Variation	[3]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[6]
Nystagmus 1, congenital, X-linked	DISXIA78	Strong	X-linked	[7]
Ocular albinism	DIS5IHK1	Strong	Biomarker	[8]
Pathologic nystagmus	DIS1QSPO	Strong	Genetic Variation	[9]
Acquired nystagmus	DISMYF5H	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of FERM domain-containing protein 7 (FRMD7).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of FERM domain-containing protein 7 (FRMD7).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of FERM domain-containing protein 7 (FRMD7).	[11]

References

• [1] Foveal development and nystagmus.Ann N Y Acad Sci. 2011 Sep;1233:292-7. doi: 10.1111/j.1749-6632.2011.06174.x.
• [2] Aetiology of infantile nystagmus.Curr Opin Neurol. 2014 Feb;27(1):83-91. doi: 10.1097/WCO.0000000000000058.
• [3] Prolonged pursuit by optokinetic drum testing in asymptomatic female carriers of novel FRMD7 splice mutation c.1050 +5 G>A.Arch Ophthalmol. 2011 Jul;129(7):936-40. doi: 10.1001/archophthalmol.2011.166.
• [4] Screening for cystic fibrosis in New York State: considerations for algorithm improvements.Eur J Pediatr. 2016 Feb;175(2):181-93. doi: 10.1007/s00431-015-2616-3. Epub 2015 Aug 21.
• [5] The assessment of data sources for influenza virologic surveillance in New York State.Influenza Other Respir Viruses. 2017 Mar;11(2):138-147. doi: 10.1111/irv.12433. Epub 2016 Nov 14.
• [6] Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene.Exp Ther Med. 2017 Sep;14(3):2277-2283. doi: 10.3892/etm.2017.4730. Epub 2017 Jul 9.
• [7] Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat Genet. 2006 Nov;38(11):1242-4. doi: 10.1038/ng1893. Epub 2006 Oct 1.
• [8] Clinical and molecular findings of FRMD7 related congenital nystagmus as adifferential diagnosis of ocular albinism.Ophthalmic Genet. 2019 Apr;40(2):161-164. doi: 10.1080/13816810.2019.1592201. Epub 2019 Apr 3.
• [9] A Disease-Causing FRMD7 Variant in a Chinese Family with Infantile Nystagmus.J Mol Neurosci. 2019 Mar;67(3):418-423. doi: 10.1007/s12031-018-1245-5. Epub 2019 Jan 8.
• [10] 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.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] 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.