Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPUTR2K)

DOT Name Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A)
Synonyms GMP-PDE alpha; EC 3.1.4.35; PDE V-B1
Gene Name PDE6A
Related Disease
Inherited retinal dystrophy ( )
Retinitis pigmentosa 43 ( )
Night blindness ( )
Movement disorder ( )
Retinitis pigmentosa ( )
UniProt ID
PDE6A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.4.35
Pfam ID
PF01590 ; PF00233
Sequence
MGEVTAEEVEKFLDSNIGFAKQYYNLHYRAKLISDLLGAKEAAVDFSNYHSPSSMEESEI
IFDLLRDFQENLQTEKCIFNVMKKLCFLLQADRMSLFMYRTRNGIAELATRLFNVHKDAV
LEDCLVMPDQEIVFPLDMGIVGHVAHSKKIANVPNTEEDEHFCDFVDILTEYKTKNILAS
PIMNGKDVVAIIMAVNKVDGSHFTKRDEEILLKYLNFANLIMKVYHLSYLHNCETRRGQI
LLWSGSKVFEELTDIERQFHKALYTVRAFLNCDRYSVGLLDMTKQKEFFDVWPVLMGEVP
PYSGPRTPDGREINFYKVIDYILHGKEDIKVIPNPPPDHWALVSGLPAYVAQNGLICNIM
NAPAEDFFAFQKEPLDESGWMIKNVLSMPIVNKKEEIVGVATFYNRKDGKPFDEMDETLM
ESLTQFLGWSVLNPDTYESMNKLENRKDIFQDIVKYHVKCDNEEIQKILKTREVYGKEPW
ECEEEELAEILQAELPDADKYEINKFHFSDLPLTELELVKCGIQMYYELKVVDKFHIPQE
ALVRFMYSLSKGYRKITYHNWRHGFNVGQTMFSLLVTGKLKRYFTDLEALAMVTAAFCHD
IDHRGTNNLYQMKSQNPLAKLHGSSILERHHLEFGKTLLRDESLNIFQNLNRRQHEHAIH
MMDIAIIATDLALYFKKRTMFQKIVDQSKTYESEQEWTQYMMLEQTRKEIVMAMMMTACD
LSAITKPWEVQSQVALLVAAEFWEQGDLERTVLQQNPIPMMDRNKADELPKLQVGFIDFV
CTFVYKEFSRFHEEITPMLDGITNNRKEWKALADEYDAKMKVQEEKKQKQQSAKSAAAGN
QPGGNPSPGGATTSKSCCIQ
Function Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3',5'-cyclic GMP. This protein participates in processes of transmission and amplification of the visual signal.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
Phototransduction (hsa04744 )
Reactome Pathway
Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859 )
Ca2+ pathway (R-HSA-4086398 )
Activation of the phototransduction cascade (R-HSA-2485179 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Inherited retinal dystrophy DISGGL77 Definitive Autosomal recessive [1]
Retinitis pigmentosa 43 DISVH54A Definitive Autosomal recessive [2]
Night blindness DIS335K9 Strong Biomarker [3]
Movement disorder DISOJJ2D moderate CausalMutation [4]
Retinitis pigmentosa DISCGPY8 Supportive Autosomal dominant [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A). [8]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A). [7]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (PDE6A). [9]
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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 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
3 Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B.JAMA Ophthalmol. 2019 Jun 1;137(6):669-679. doi: 10.1001/jamaophthalmol.2018.6367.
4 Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families.Mol Vis. 2015 Aug 18;21:871-82. eCollection 2015.
5 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.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 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.
9 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.