Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHY9ZA5)

• DOT Name: Membrane frizzled-related protein (MFRP)
• Synonyms: Membrane-type frizzled-related protein
• Gene Name: MFRP
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Coronary heart disease
  Isolated microphthalmia 5
  Nanophthalmos 2
  Age-related macular degeneration
  Atrial fibrillation
  Disorder of glycogen metabolism
  Disorder of orbital region
  Fatty liver disease
  Fundus albipunctatus
  Macular degeneration
  Metabolic disorder
  Non-insulin dependent diabetes
  Obesity
  Primary angle-closure glaucoma
  Proliferative diabetic retinopathy
  Retinal degeneration
  Retinitis pigmentosa
  Trichohepatoenteric syndrome
  Type-1/2 diabetes
  X-linked reticulate pigmentary disorder
  Late-onset retinal degeneration
  Nanophthalmia
  Doyne honeycomb retinal dystrophy
  Sorsby fundus dystrophy
  Vitelliform macular dystrophy
• UniProt ID: MFRP_HUMAN
• Pfam ID: PF00431 ; PF01392 ; PF00057
• Sequence:
  MKDFSDVILCMEATESSKTEFCNPAFEPESGPPCPPPVFPEDASYSVPAPWHGRRPRGLR
  PDCRFSWLCVLLLSSLLLLLLGLLVAIILAQLQAAPPSGASHSPLPAGGLTTTTTTPTIT
  TSQAAGTPKGQQESGVSPSPQSTCGGLLSGPRGFFSSPNYPDPYPPNTHCVWHIQVATDH
  AIQLKIEALSIESVASCLFDRLELSPEPEGPLLRVCGRVPPPTLNTNASHLLVVFVSDSS
  VEGFGFHAWYQAMAPGRGSCAHDEFRCDQLICLLPDSVCDGFANCADGSDETNCSAKFSG
  CGGNLTGLQGTFSTPSYLQQYPHQLLCTWHISVPAGHSIELQFHNFSLEAQDECKFDYVE
  VYETSSSGAFSLLGRFCGAEPPPHLVSSHHELAVLFRTDHGISSGGFSATYLAFNATENP
  CGPSELSCQAGGCKGVQWMCDMWRDCTDGSDDNCSGPLFPPPELACEPVQVEMCLGLSYN
  TTAFPNIWVGMITQEEVVEVLSGYKSLTSLPCYQHFRRLLCGLLVPRCTPLGSVLPPCRS
  VCQEAEHQCQSGLALLGTPWPFNCNRLPEAADLEACAQP
• Function: May play a role in eye development.
• Tissue Specificity: Specifically expressed in brain. Strongly expressed in medulla oblongata and to a lower extent in hippocampus and corpus callosum. Expressed in keratinocytes.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Biomarker	[1]
Atherosclerosis	DISMN9J3	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Definitive	Altered Expression	[1]
Isolated microphthalmia 5	DISQQJMC	Definitive	Autosomal recessive	[2]
Nanophthalmos 2	DISCVMI9	Definitive	Autosomal recessive	[3]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[4]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[5]
Disorder of glycogen metabolism	DISYGNOB	Strong	Biomarker	[6]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[8]
Fundus albipunctatus	DISNICY6	Strong	Biomarker	[9]
Macular degeneration	DISLKKHD	Strong	Genetic Variation	[4]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[10]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[11]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[13]
Proliferative diabetic retinopathy	DISQZ13G	Strong	Biomarker	[11]
Retinal degeneration	DISM1JHQ	Strong	Biomarker	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[14]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[12]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Biomarker	[11]
Late-onset retinal degeneration	DIST9GP4	moderate	Biomarker	[15]
Nanophthalmia	DISIULDO	Supportive	Autosomal dominant	[16]
Doyne honeycomb retinal dystrophy	DISKFNCT	Limited	Genetic Variation	[17]
Sorsby fundus dystrophy	DISFVBJE	Limited	Genetic Variation	[17]
Vitelliform macular dystrophy	DISEFYYN	Limited	Genetic Variation	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Membrane frizzled-related protein (MFRP).	[18]

1 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 increases the methylation of Membrane frizzled-related protein (MFRP).	[19]

References

• [1] CTRP5 promotes transcytosis and oxidative modification of low-density lipoprotein and the development of atherosclerosis.Atherosclerosis. 2018 Nov;278:197-209. doi: 10.1016/j.atherosclerosis.2018.09.037. Epub 2018 Sep 28.
• [2] A new autosomal recessive syndrome consisting of posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disc drusen is caused by a MFRP gene mutation. Mol Vis. 2006 Dec 4;12:1483-9.
• [3] A novel mutation confirms MFRP as the gene causing the syndrome of nanophthalmos-renititis pigmentosa-foveoschisis-optic disk drusen. Am J Ophthalmol. 2008 Aug;146(2):323-328. doi: 10.1016/j.ajo.2008.04.029. Epub 2008 Jun 13.
• [4] Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation.Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3363-71. doi: 10.1167/iovs.05-0159.
• [5] Presence of rd8 mutation does not alter the ocular phenotype of late-onset retinal degeneration mouse model.Mol Vis. 2015 Mar 13;21:273-84. eCollection 2015.
• [6] Co-inheritance of the membrane frizzled-related protein ocular phenotype and glycogen storage disease type Ib.Ophthalmic Genet. 2017 Dec;38(6):544-548. doi: 10.1080/13816810.2017.1323340. Epub 2017 May 16.
• [7] Coexistence of KCNV2 associated cone dystrophy with supernormal rod electroretinogram and MFRP related oculopathy in a Turkish family.Br J Ophthalmol. 2013 Feb;97(2):169-73. doi: 10.1136/bjophthalmol-2012-302355. Epub 2012 Nov 10.
• [8] Loss of CTRP5 improves insulin action and hepatic steatosis.Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E1036-52. doi: 10.1152/ajpendo.00010.2016. Epub 2016 May 3.
• [9] Retinal degeneration 6 (rd6): a new mouse model for human retinitis punctata albescens.Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3149-57.
• [10] The novel adipokine CTRP5 is a negative regulator of white adipose tissue browning.Biochem Biophys Res Commun. 2019 Mar 12;510(3):388-394. doi: 10.1016/j.bbrc.2019.01.111. Epub 2019 Feb 1.
• [11] CTRP3 is a novel biomarker for diabetic retinopathy and inhibits HGHL-induced VCAM-1 expression in an AMPK-dependent manner.PLoS One. 2017 Jun 20;12(6):e0178253. doi: 10.1371/journal.pone.0178253. eCollection 2017.
• [12] Circulating complement-1q tumor necrosis factor--related protein isoform5 levels are low in type2 diabetes patients and reduced by dapagliflozin.J Diabetes Investig. 2020 Jan;11(1):88-95. doi: 10.1111/jdi.13069. Epub 2019 Jun 6.
• [13] Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population.BMC Ophthalmol. 2018 Oct 22;18(1):271. doi: 10.1186/s12886-018-0934-8.
• [14] Posterior microphthalmos, retinitis pigmentosa, and foveoschisis caused by a mutation in the MFRP gene: a familial study.Ophthalmic Genet. 2019 Jun;40(3):288-292. doi: 10.1080/13816810.2019.1633547. Epub 2019 Jul 2.
• [15] Late-onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1.Aging Cell. 2019 Dec;18(6):e13011. doi: 10.1111/acel.13011. Epub 2019 Aug 5.
• [16] Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9553-8. doi: 10.1073/pnas.0501451102. Epub 2005 Jun 23.
• [17] Molecular diagnostic testing by eyeGENE: analysis of patients with hereditary retinal dystrophy phenotypes involving central vision loss.Invest Ophthalmol Vis Sci. 2014 Jul 31;55(9):5510-21. doi: 10.1167/iovs.14-14359.
• [18] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [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.