Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT81UJI0)

DOT Name Retinal guanylyl cyclase 1 (GUCY2D)
Synonyms RETGC-1; EC 4.6.1.2; CG-E; Guanylate cyclase 2D, retinal; Rod outer segment membrane guanylate cyclase; ROS-GC
Gene Name GUCY2D
Related Disease
GUCY2D-related dominant retinopathy ( )
GUCY2D-related recessive retinopathy ( )
Leber congenital amaurosis 1 ( )
Cone-rod dystrophy 6 ( )
Night blindness, congenital stationary, type1i ( )
Choroidal dystrophy ( )
Cone-rod dystrophy ( )
Leber congenital amaurosis ( )
UniProt ID
GUC2D_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
4.6.1.2
Pfam ID
PF01094 ; PF00211 ; PF07701 ; PF07714
Sequence
MTACARRAGGLPDPGLCGPAWWAPSLPRLPRALPRLPLLLLLLLLQPPALSAVFTVGVLG
PWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALAR
VSGLVGPVNPAACRPAELLAEEAGIALVPWGCPWTQAEGTTAPAVTPAADALYALLRAFG
WARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPLDLSGAREALRKVRDGPRVT
AVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEALAALANSSQ
LRRAHDAVLTLTRHCPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLARG
VAEARAAAGGRWVSGAAVARHIRDAQVPGFCGDLGGDEEPPFVLLDTDAAGDRLFATYML
DPARGSFLSAGTRMHFPRGGSAPGPDPSCWFDPNNICGGGLEPGLVFLGFLLVVGMGLAG
AFLAHYVRHRLLHMQMVSGPNKIILTVDDITFLHPHGGTSRKVAQGSRSSLGARSMSDIR
SGPSQHLDSPNIGVYEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFL
ARGAEGPAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHR
GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPALE
RRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMDQAPVEC
ILLMKQCWAEQPELRPSMDHTFDLFKNINKGRKTNIIDSMLRMLEQYSSNLEDLIRERTE
ELELEKQKTDRLLTQMLPPSVAEALKTGTPVEPEYFEQVTLYFSDIVGFTTISAMSEPIE
VVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAV
GTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHV
NLSTVGILRALDSGYQVELRGRTELKGKGAEDTFWLVGRRGFNKPIPKPPDLQPGSSNHG
ISLQEIPPERRRKLEKARPGQFS
Function
Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors. Plays an essential role in phototransduction, by mediating cGMP replenishment. May also participate in the trafficking of membrane-asociated proteins to the photoreceptor outer segment membrane.
Tissue Specificity Retina.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
Olfactory transduction (hsa04740 )
Phototransduction (hsa04744 )
Reactome Pathway
Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
GUCY2D-related dominant retinopathy DIS5FIOZ Definitive Autosomal dominant [1]
GUCY2D-related recessive retinopathy DISR72NR Definitive Autosomal recessive [1]
Leber congenital amaurosis 1 DISY2B33 Definitive Autosomal recessive [2]
Cone-rod dystrophy 6 DISNS9U8 Strong Autosomal dominant [3]
Night blindness, congenital stationary, type1i DISM03XG Strong Autosomal recessive [4]
Choroidal dystrophy DISWIF1T Supportive Autosomal dominant [5]
Cone-rod dystrophy DISY9RWN Supportive Autosomal dominant [6]
Leber congenital amaurosis DISMGH8F Supportive Autosomal dominant [7]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Retinal guanylyl cyclase 1 (GUCY2D). [8]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Retinal guanylyl cyclase 1 (GUCY2D). [9]
Gefitinib DM15F0X Approved Gefitinib decreases the expression of Retinal guanylyl cyclase 1 (GUCY2D). [10]
ORG2058 DMH1M6N Investigative ORG2058 increases the expression of Retinal guanylyl cyclase 1 (GUCY2D). [12]
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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 decreases the methylation of Retinal guanylyl cyclase 1 (GUCY2D). [11]
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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 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy. Hum Mol Genet. 2000 Dec 12;9(20):3065-73. doi: 10.1093/hmg/9.20.3065.
4 Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D. Am J Ophthalmol. 2018 Jun;190:58-68. doi: 10.1016/j.ajo.2018.03.021. Epub 2018 Mar 17.
5 A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy. Invest Ophthalmol Vis Sci. 2012 Jul 12;53(8):4748-53. doi: 10.1167/iovs.12-10061.
6 A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis. Eur J Hum Genet. 2010 Oct;18(10):1121-6. doi: 10.1038/ejhg.2010.81. Epub 2010 Jun 2.
7 Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015 Feb 16;3(2):112-24. doi: 10.12998/wjcc.v3.i2.112.
8 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
9 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.
10 Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
11 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.
12 The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.