Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7EVWQ)

DOT Name Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C)
Synonyms EC 3.1.4.35; cGMP phosphodiesterase 6C
Gene Name PDE6C
Related Disease
Cone dystrophy 4 ( )
Inherited retinal dystrophy ( )
Retinopathy ( )
Blue cone monochromacy ( )
Achromatopsia ( )
Cone dystrophy ( )
UniProt ID
PDE6C_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3JWQ; 3JWR; 5E8F
EC Number
3.1.4.35
Pfam ID
PF01590 ; PF00233
Sequence
MGEINQVAVEKYLEENPQFAKEYFDRKLRVEVLGEIFKNSQVPVQSSMSFSELTQVEESA
LCLELLWTVQEEGGTPEQGVHRALQRLAHLLQADRCSMFLCRSRNGIPEVASRLLDVTPT
SKFEDNLVGPDKEVVFPLDIGIVGWAAHTKKTHNVPDVKKNSHFSDFMDKQTGYVTKNLL
ATPIVVGKEVLAVIMAVNKVNASEFSKQDEEVFSKYLNFVSIILRLHHTSYMYNIESRRS
QILMWSANKVFEELTDVERQFHKALYTVRSYLNCERYSIGLLDMTKEKEFYDEWPIKLGE
VEPYKGPKTPDGREVNFYKIIDYILHGKEEIKVIPTPPADHWTLISGLPTYVAENGFICN
MMNAPADEYFTFQKGPVDETGWVIKNVLSLPIVNKKEDIVGVATFYNRKDGKPFDEHDEY
ITETLTQFLGWSLLNTDTYDKMNKLENRKDIAQEMLMNQTKATPEEIKSILKFQEKLNVD
VIDDCEEKQLVAILKEDLPDPRSAELYEFRFSDFPLTEHGLIKCGIRLFFEINVVEKFKV
PVEVLTRWMYTVRKGYRAVTYHNWRHGFNVGQTMFTLLMTGRLKKYYTDLEAFAMLAAAF
CHDIDHRGTNNLYQMKSTSPLARLHGSSILERHHLEYSKTLLQDESLNIFQNLNKRQFET
VIHLFEVAIIATDLALYFKKRTMFQKIVDACEQMQTEEEAIKYVTVDPTKKEIIMAMMMT
ACDLSAITKPWEVQSQVALMVANEFWEQGDLERTVLQQQPIPMMDRNKRDELPKLQVGFI
DFVCTFVYKEFSRFHKEITPMLSGLQNNRVEWKSLADEYDAKMKVIEEEAKKQEGGAEKA
AEDSGGGDDKKSKTCLML
Function As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cone dystrophy 4 DISIOY2J Definitive Autosomal recessive [1]
Inherited retinal dystrophy DISGGL77 Definitive Autosomal recessive [2]
Retinopathy DISB4B0F Strong Biomarker [3]
Blue cone monochromacy DISYV7KB moderate Genetic Variation [4]
Achromatopsia DISKL51I Supportive Autosomal recessive [4]
Cone dystrophy DIS7SAZZ Supportive Autosomal dominant [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methamphetamine DMPM4SK Approved Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C) affects the response to substance of Methamphetamine. [10]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C). [5]
Phenobarbital DMXZOCG Approved Phenobarbital decreases the expression of Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C). [6]
Malathion DMXZ84M Approved Malathion decreases the expression of Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C). [7]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C). [9]
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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 Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (PDE6C). [8]
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References

1 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.
2 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.
3 Deep Phenotyping of PDE6C-Associated Achromatopsia.Invest Ophthalmol Vis Sci. 2019 Dec 2;60(15):5112-5123. doi: 10.1167/iovs.19-27761.
4 Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet. 2009 Aug;85(2):240-7. doi: 10.1016/j.ajhg.2009.06.016. Epub 2009 Jul 16.
5 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
6 Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
7 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
8 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.
9 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
10 Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.