Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6VUH78)

• DOT Name: Peripherin (PRPH)
• Synonyms: Neurofilament 4
• Gene Name: PRPH
• Related Disease:
  Age-related macular degeneration
  Multifocal pattern dystrophy simulating fundus flavimaculatus
  Neuroblastoma
  Adult-onset foveomacular vitelliform dystrophy
  Cone dystrophy
  Cone-rod dystrophy
  Cone-rod dystrophy 2
  Giant axonal neuropathy 1
  Inherited retinal dystrophy
  Leber congenital amaurosis
  Motor neurone disease
  Peripheral neuropathy
  Retinitis pigmentosa
  Retinitis pigmentosa 7
  Retinopathy
  Stargardt disease
  X-linked reticulate pigmentary disorder
  Retinitis punctata albescens
  Amyotrophic lateral sclerosis
  Choroidal dystrophy
  Congenital alveolar dysplasia
  Hereditary macular dystrophy
  Spinocerebellar ataxia
• UniProt ID: PERI_HUMAN
• Pfam ID: PF00038 ; PF04732
• Sequence:
  MSHHPSGLRAGFSSTSYRRTFGPPPSLSPGAFSYSSSSRFSSSRLLGSASPSSSVRLGSF
  RSPRAGAGALLRLPSERLDFSMAEALNQEFLATRSNEKQELQELNDRFANFIEKVRFLEQ
  QNAALRGELSQARGQEPARADQLCQQELRELRRELELLGRERDRVQVERDGLAEDLAALK
  QRLEEETRKREDAEHNLVLFRKDVDDATLSRLELERKIESLMDEIEFLKKLHEEELRDLQ
  VSVESQQVQQVEVEATVKPELTAALRDIRAQYESIAAKNLQEAEEWYKSKYADLSDAANR
  NHEALRQAKQEMNESRRQIQSLTCEVDGLRGTNEALLRQLRELEEQFALEAGGYQAGAAR
  LEEELRQLKEEMARHLREYQELLNVKMALDIEIATYRKLLEGEESRISVPVHSFASLNIK
  TTVPEVEPPQDSHSRKTVLIKTIETRNGEVVTESQKEQRSELDKSSAHSY
• Function: Class-III neuronal intermediate filament protein. May form an independent structural network without the involvement of other neurofilaments or may cooperate with the neuronal intermediate filament proteins NEFL, NEFH, NEFM and INA to form a filamentous network. Assembly of the neuronal intermediate filaments may be regulated by RAB7A. Plays a role in the development of unmyelinated sensory neurons. May be involved in axon elongation and axon regeneration after injury. Inhibits neurite extension in type II spiral ganglion neurons in the cochlea.
• Tissue Specificity: Expressed in the neurons of the outer hair cells in the organ of Corti and to a lesser extent in type I spiral ganglion cells.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Definitive	Genetic Variation	[1]
Multifocal pattern dystrophy simulating fundus flavimaculatus	DISBMVDE	Definitive	Genetic Variation	[2]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[3]
Adult-onset foveomacular vitelliform dystrophy	DISPYJN2	Strong	Genetic Variation	[4]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[5]
Cone-rod dystrophy	DISY9RWN	Strong	Genetic Variation	[6]
Cone-rod dystrophy 2	DISX2RWY	Strong	Genetic Variation	[6]
Giant axonal neuropathy 1	DIS3H1TR	Strong	Altered Expression	[7]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[8]
Leber congenital amaurosis	DISMGH8F	Strong	Genetic Variation	[9]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[10]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[11]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[12]
Retinitis pigmentosa 7	DISP0YU7	Strong	Biomarker	[13]
Retinopathy	DISB4B0F	Strong	Genetic Variation	[14]
Stargardt disease	DISPXOTO	Strong	Genetic Variation	[15]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Genetic Variation	[16]
Retinitis punctata albescens	DISVJAI4	moderate	Genetic Variation	[17]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Autosomal dominant	[18]
Choroidal dystrophy	DISWIF1T	Limited	Genetic Variation	[19]
Congenital alveolar dysplasia	DIS1IYUN	Limited	Genetic Variation	[20]
Hereditary macular dystrophy	DISEYSYY	Limited	Genetic Variation	[21]
Spinocerebellar ataxia	DISYMHUK	Limited	Genetic Variation	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Peripherin (PRPH) affects the binding of Sulforaphane.	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Peripherin (PRPH).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Peripherin (PRPH).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Peripherin (PRPH).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peripherin (PRPH).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Peripherin (PRPH).	[27]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Peripherin (PRPH).	[28]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Peripherin (PRPH).	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Peripherin (PRPH).	[29]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Peripherin (PRPH).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Peripherin (PRPH).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Peripherin (PRPH).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Peripherin (PRPH).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peripherin (PRPH).	[34]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Peripherin (PRPH).	[35]

References

• [1] PRPH2 (Peripherin/RDS) mutations associated with different macular dystrophies in a Spanish population: a new mutation.Eur J Ophthalmol. 2010 Jul-Aug;20(4):724-32. doi: 10.1177/112067211002000413.
• [2] Mutations in the peripherin/RDS gene are an important cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus. Br J Ophthalmol. 2007 Nov;91(11):1504-11. doi: 10.1136/bjo.2007.115659. Epub 2007 May 15.
• [3] A comparative immunohistochemical analysis of small round cell tumors of childhood: utility of peripherin and alpha-internexin as markers for neuroblastomas.Appl Immunohistochem Mol Morphol. 2008 Jul;16(4):344-8. doi: 10.1097/PAI.0b013e318165fe78.
• [4] Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene.Eur J Ophthalmol. 2007 Nov-Dec;17(6):1000-3. doi: 10.1177/112067210701700624.
• [5] Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy.Ophthalmology. 1997 Feb;104(2):299-306. doi: 10.1016/s0161-6420(97)30320-0.
• [6] Autosomal dominant cone-rod dystrophy associated with a Val200Glu mutation of the peripherin/RDS gene.Retina. 1996;16(5):405-10. doi: 10.1097/00006982-199616050-00007.
• [7] Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin.Hum Mol Genet. 2015 Mar 1;24(5):1420-31. doi: 10.1093/hmg/ddu556. Epub 2014 Nov 4.
• [8] Intrafamilial clinical heterogeneity associated with a novel mutation of the retinal degeneration slow/peripherin gene.Ophthalmic Res. 2007;39(5):255-9. doi: 10.1159/000108118. Epub 2007 Sep 12.
• [9] Peripherin mutations cause a distinct form of recessive Leber congenital amaurosis and dominant phenotypes in asymptomatic parents heterozygous for the mutation. Br J Ophthalmol. 2016 Feb;100(2):209-15. doi: 10.1136/bjophthalmol-2015-306844. Epub 2015 Jun 10.
• [10] A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis.Brain Pathol. 2004 Jul;14(3):290-6. doi: 10.1111/j.1750-3639.2004.tb00066.x.
• [11] A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy.Nat Commun. 2019 Apr 16;10(1):1777. doi: 10.1038/s41467-019-09719-4.
• [12] Molecular screening of rhodopsin and peripherin/RDS genes in Mexican families with autosomal dominant retinitis pigmentosa.Curr Eye Res. 2009 Dec;34(12):1050-6. doi: 10.3109/02713680903283169.
• [13] Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa.Am J Hum Genet. 1996 Feb;58(2):347-55.
• [14] Clinical and genetic aspects of two Spanish families with autosomal dominant retinitis pigmentosa (ADRP).Ophthalmic Genet. 1996 Mar;17(1):29-33. doi: 10.3109/13816819609057866.
• [15] Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene.Arch Ophthalmol. 1993 Nov;111(11):1531-42. doi: 10.1001/archopht.1993.01090110097033.
• [16] Genetic heterogeneity in autosomal dominant pattern dystrophy of the retina.Mol Vis. 1996 Jun 20;2:6.
• [17] Identification of a polymorphic missense (G338D) and silent (106V and 121L) mutations within the coding region of the peripherin/RDS gene in a patient with retinitis punctata albescens.Biochem Biophys Res Commun. 1997 Feb 3;231(1):103-5. doi: 10.1006/bbrc.1997.6052.
• [18] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [19] Central areolar choroidal dystrophy associated with inherited drusen in a multigeneration Tunisian family: exclusion of the PRPH2 gene and the 17p13 locus.J Hum Genet. 2009 Oct;54(10):589-94. doi: 10.1038/jhg.2009.82. Epub 2009 Aug 21.
• [20] Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa.Invest Ophthalmol Vis Sci. 1997 Sep;38(10):1972-82.
• [21] Macular dystrophy associated with the Arg172Trp substitution in peripherin/RDS: genotype-phenotype correlation.Retina. 2009 May;29(5):682-8. doi: 10.1097/IAE.0b013e318198dbed.
• [22] Autosomal-dominant cerebellar ataxia with retinal degeneration (ADCA type II) is genetically different from ADCA type I.Ann Neurol. 1994 Apr;35(4):439-44. doi: 10.1002/ana.410350411.
• [23] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [24] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [29] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [30] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [31] 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.
• [32] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [33] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [34] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [35] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [36] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.