Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNH2G5H)

DOT Name	Peripherin-2 (PRPH2)
Synonyms	Retinal degeneration slow protein; Tetraspanin-22; Tspan-22
Gene Name	PRPH2
Related Disease	Inherited retinal dystrophy ( ) Leber congenital amaurosis 9 ( ) Retinitis pigmentosa 7 ( ) Adult respiratory distress syndrome ( ) Age-related macular degeneration ( ) Autosomal recessive polycystic kidney disease ( ) Choroidal dystrophy, central areolar 2 ( ) Choroidal neovascularization ( ) Cone dystrophy ( ) Disease of orbital part of eye adnexa ( ) Fundus albipunctatus ( ) Hereditary macular dystrophy ( ) Laryngeal carcinoma ( ) Late-onset Parkinson disease ( ) Leber congenital amaurosis ( ) Macular degeneration ( ) Pneumothorax ( ) Shwachman-Diamond syndrome ( ) Tuberculosis ( ) Usher syndrome ( ) Usher syndrome type 1 ( ) Vitelliform macular dystrophy 3 ( ) Pathologic nystagmus ( ) Stargardt disease ( ) Adult-onset foveomacular vitelliform dystrophy ( ) Choroidal dystrophy ( ) Cone-rod dystrophy ( ) Multifocal pattern dystrophy simulating fundus flavimaculatus ( ) Patterned macular dystrophy ( ) Retinitis pigmentosa ( ) Retinitis punctata albescens ( ) Blindness ( ) Cone-rod dystrophy 2 ( ) Congenital alveolar dysplasia ( ) Glycogen storage disease type II ( ) Hereditary pulmonary alveolar proteinosis ( ) Leber congenital amaurosis 1 ( ) Retinitis pigmentosa 1 ( ) Severe early-childhood-onset retinal dystrophy ( ) Vitelliform macular dystrophy ( )
UniProt ID	PRPH2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7ZW1
Pfam ID	PF00335
Sequence	MALLKVKFDQKKRVKLAQGLWLMNWFSVLAGIIIFSLGLFLKIELRKRSDVMNNSESHFV PNSLIGMGVLSCVFNSLAGKICYDALDPAKYARWKPWLKPYLAICVLFNIILFLVALCCF LLRGSLENTLGQGLKNGMKYYRDTDTPGRCFMKKTIDMLQIEFKCCGNNGFRDWFEIQWI SNRYLDFSSKEVKDRIKSNVDGRYLVDGVPFSCCNPSSPRPCIQYQITNNSAHYSYDHQT EELNLWVRGCRAALLSYYSSLMNSMGVVTLLIWLFEVTITIGLRYLQTSLDGVSNPEESE SESQGWLLERSVPETWKAFLESVKKLGKGNQVEAEGADAGQAPEAG
Function	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure. Required for the maintenance of retinal outer nuclear layer thickness. Required for the correct development and organization of the photoreceptor inner segment.
Tissue Specificity	Retina (photoreceptor). In rim region of ROS (rod outer segment) disks.

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Inherited retinal dystrophy	DISGGL77	Definitive	Semidominant	[1]
Leber congenital amaurosis 9	DIS35YGW	Definitive	Autosomal recessive	[2]
Retinitis pigmentosa 7	DISP0YU7	Definitive	Autosomal recessive	[3]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[5]
Autosomal recessive polycystic kidney disease	DISPUS40	Strong	Genetic Variation	[6]
Choroidal dystrophy, central areolar 2	DIS6TCKT	Strong	Autosomal dominant	[7]
Choroidal neovascularization	DISLGVL7	Strong	Genetic Variation	[8]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[9]
Disease of orbital part of eye adnexa	DISGWPWX	Strong	Biomarker	[10]
Fundus albipunctatus	DISNICY6	Strong	Autosomal dominant	[11]
Hereditary macular dystrophy	DISEYSYY	Strong	Genetic Variation	[12]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[13]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[14]
Leber congenital amaurosis	DISMGH8F	Strong	Genetic Variation	[2]
Macular degeneration	DISLKKHD	Strong	Genetic Variation	[15]
Pneumothorax	DISP86H1	Strong	Biomarker	[16]
Shwachman-Diamond syndrome	DISW57NW	Strong	Biomarker	[17]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[18]
Usher syndrome	DIS9YIS7	Strong	Genetic Variation	[19]
Usher syndrome type 1	DISR29E4	Strong	Biomarker	[19]
Vitelliform macular dystrophy 3	DISE6D4P	Strong	Autosomal dominant	[7]
Pathologic nystagmus	DIS1QSPO	moderate	Genetic Variation	[2]
Stargardt disease	DISPXOTO	moderate	Genetic Variation	[20]
Adult-onset foveomacular vitelliform dystrophy	DISPYJN2	Supportive	Autosomal dominant	[21]
Choroidal dystrophy	DISWIF1T	Supportive	Autosomal dominant	[22]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[23]
Multifocal pattern dystrophy simulating fundus flavimaculatus	DISBMVDE	Supportive	Autosomal dominant	[24]
Patterned macular dystrophy	DISWIXVD	Supportive	Autosomal dominant	[25]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[26]
Retinitis punctata albescens	DISVJAI4	Supportive	Autosomal dominant	[11]
Blindness	DISTIM10	Limited	Genetic Variation	[27]
Cone-rod dystrophy 2	DISX2RWY	Limited	Genetic Variation	[14]
Congenital alveolar dysplasia	DIS1IYUN	Limited	Biomarker	[4]
Glycogen storage disease type II	DISXZPBC	Limited	Biomarker	[28]
Hereditary pulmonary alveolar proteinosis	DISQC53I	Limited	Genetic Variation	[29]
Leber congenital amaurosis 1	DISY2B33	Limited	Genetic Variation	[30]
Retinitis pigmentosa 1	DISSLQPP	Limited	Biomarker	[31]
Severe early-childhood-onset retinal dystrophy	DISFDRFO	Limited	Genetic Variation	[32]
Vitelliform macular dystrophy	DISEFYYN	Limited	Genetic Variation	[33]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Peripherin-2 (PRPH2).	[34]
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References

1	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.
2	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.
3	Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res. 2013 Feb;23(2):236-47. doi: 10.1101/gr.144105.112. Epub 2012 Oct 26.
4	A new low-cost commercial bubble CPAP (bCPAP) machine compared with a traditional bCPAP device in Nigeria.Paediatr Int Child Health. 2019 Aug;39(3):184-192. doi: 10.1080/20469047.2019.1598125. Epub 2019 Apr 8.
5	A Specific Macula-Predominant Retinal Phenotype Is Associated With the CDHR1 Variant c.783G>A, a Silent Mutation Leading to In-Frame Exon Skipping.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3388-3397. doi: 10.1167/iovs.18-26415.
6	Fine mapping of the autosomal recessive polycystic kidney disease locus (PKHD1) and the genes MUT, RDS, CSNK2 beta, and GSTA1 at 6p21.1-p12.Genomics. 1998 Feb 15;48(1):40-5. doi: 10.1006/geno.1997.5145.
7	[Phenotypic variation in a family affected by autosomal dominant retinal dystrophy caused by the Gly208Asp mutation in the RDS peripherin gene]. Med Clin (Barc). 2002 May 18;118(18):716. doi: 10.1016/s0025-7753(02)72505-0.
8	Choroidal neovascularization in patients with adult-onset foveomacular dystrophy caused by mutations in the RDS/peripherin gene.Adv Exp Med Biol. 2006;572:35-40. doi: 10.1007/0-387-32442-9_6.
9	The Late Endosomal Pathway Regulates the Ciliary Targeting of Tetraspanin Protein Peripherin 2.J Neurosci. 2019 May 1;39(18):3376-3393. doi: 10.1523/JNEUROSCI.2811-18.2019. Epub 2019 Feb 28.
10	Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights from a Highly Derived Visual Phenotype.Genome Biol Evol. 2019 Aug 1;11(8):2244-2255. doi: 10.1093/gbe/evz111.
11	A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens. Nat Genet. 1993 Mar;3(3):208-12. doi: 10.1038/ng0393-208.
12	Oligomerization of Prph2 and Rom1 is essential for photoreceptor outer segment formation.Hum Mol Genet. 2018 Oct 15;27(20):3507-3518. doi: 10.1093/hmg/ddy240.
13	PRPH2 Activates Hippo Signalling and Suppresses the Invasion and Anoikis Inhibition of Laryngeal Cancer.Cancer Manag Res. 2019 Dec 2;11:10107-10115. doi: 10.2147/CMAR.S222527. eCollection 2019.
14	Autosomal Dominant Retinal Dystrophies Caused by a Founder Splice Site Mutation, c.828+3A>T, in PRPH2 and Protein Haplotypes in trans as Modifiers.Invest Ophthalmol Vis Sci. 2016 Feb;57(2):349-59. doi: 10.1167/iovs.15-16965.
15	Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS.Hum Mol Genet. 2014 Jun 15;23(12):3102-14. doi: 10.1093/hmg/ddu014. Epub 2014 Jan 25.
16	Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants.Early Hum Dev. 2018 Jan;116:1-8. doi: 10.1016/j.earlhumdev.2017.08.010. Epub 2017 Nov 5.
17	Pullulanase treatments to increase resistant starch content of black chickpea (Cicer arietinum L.) starch and the effects on starch properties.Int J Biol Macromol. 2018 May;111:505-513. doi: 10.1016/j.ijbiomac.2018.01.026. Epub 2018 Jan 7.
18	Assessing and screening for T-cell epitopes from Mycobacterium tuberculosis RD2 proteins for the diagnosis of active tuberculosis.Braz J Infect Dis. 2018 Nov-Dec;22(6):462-471. doi: 10.1016/j.bjid.2018.10.280. Epub 2018 Dec 5.
19	Combination of retinitis pigmentosa and hearing loss caused by a novel mutation in PRPH2 and a known mutation in GJB2: importance for differential diagnosis of Usher syndrome.Vision Res. 2012 Dec 15;75:71-6. doi: 10.1016/j.visres.2012.07.011. Epub 2012 Jul 25.
20	The K153Del PRPH2 mutation differentially impacts photoreceptor structure and function.Hum Mol Genet. 2016 Aug 15;25(16):3500-3514. doi: 10.1093/hmg/ddw193. Epub 2016 Jun 29.
21	Adult vitelliform macular dystrophy is frequently associated with mutations in the peripherin/RDS gene. Hum Mutat. 1997;10(4):301-9. doi: 10.1002/(SICI)1098-1004(1997)10:4<301::AID-HUMU6>3.0.CO;2-J.
22	Autosomal dominant central areolar choroidal dystrophy and a novel Arg195Leu mutation in the peripherin/RDS gene. Arch Ophthalmol. 2003 Oct;121(10):1458-61. doi: 10.1001/archopht.121.10.1458.
23	RDS/peripherin gene mutations are frequent causes of central retinal dystrophies. J Med Genet. 1997 Aug;34(8):620-6. doi: 10.1136/jmg.34.8.620.
24	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.
25	Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. Nat Genet. 1993 Mar;3(3):202-7. doi: 10.1038/ng0393-202.
26	Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
27	Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice.J Neurosci. 2000 Mar 15;20(6):2150-4. doi: 10.1523/JNEUROSCI.20-06-02150.2000.
28	Genetic screening for macular dystrophies in patients clinically diagnosed with dry age-related macular degeneration.Clin Genet. 2018 Dec;94(6):569-574. doi: 10.1111/cge.13447. Epub 2018 Oct 15.
29	Surfactant proteins gene variants in premature newborn infants with severe respiratory distress syndrome.J Perinatol. 2018 Apr;38(4):337-344. doi: 10.1038/s41372-017-0018-2. Epub 2017 Dec 19.
30	Comprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing.J Med Genet. 2013 Oct;50(10):674-88. doi: 10.1136/jmedgenet-2013-101558. Epub 2013 Jul 11.
31	Microarray-based mutation detection and phenotypic characterization in Korean patients with retinitis pigmentosa.Mol Vis. 2012;18:2398-410. Epub 2012 Sep 25.
32	Evaluation of the ELOVL4, PRPH2 and ABCA4 genes in patients with Stargardt macular degeneration.Mol Med Rep. 2012 Nov;6(5):1045-9. doi: 10.3892/mmr.2012.1063. Epub 2012 Sep 4.
33	Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
34	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.