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Aliases for PDE5A Gene

Aliases for PDE5A Gene

  • Phosphodiesterase 5A 2 3 5
  • Phosphodiesterase 5A, CGMP-Specific 2 3
  • CGB-PDE 3 4
  • PDE5 3 4
  • CGMP-Binding CGMP-Specific 3,5-Cyclic Nucleotide Phosphodiesterase 3
  • CGMP-Binding CGMP-Specific Phosphodiesterase 4
  • CGMP-Specific 3,5-Cyclic Phosphodiesterase 3
  • CGMP-Specific Phosphodiesterase Type 5A 3
  • CGMP-Specific Phosphodiesterase PDE5A2 3
  • Phosphodiesterase Isozyme 5 3
  • EC 3.1.4.35 4
  • CN5A 3

External Ids for PDE5A Gene

Previous GeneCards Identifiers for PDE5A Gene

  • GC04M121176
  • GC04M120698
  • GC04M120811
  • GC04M120877
  • GC04M120878
  • GC04M120776
  • GC04M120415
  • GC04M116136

Summaries for PDE5A Gene

Entrez Gene Summary for PDE5A Gene

  • This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for PDE5A Gene

PDE5A (Phosphodiesterase 5A) is a Protein Coding gene. Diseases associated with PDE5A include Priapism and Nonarteritic Anterior Ischemic Optic Neuropathy. Among its related pathways are NO-dependent CFTR activation (normal and CF) and Pyrimidine metabolism (KEGG). Gene Ontology (GO) annotations related to this gene include 3,5-cyclic-nucleotide phosphodiesterase activity and 3,5-cyclic-GMP phosphodiesterase activity. An important paralog of this gene is PDE11A.

UniProtKB/Swiss-Prot for PDE5A Gene

  • Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).

Tocris Summary for PDE5A Gene

  • Phosphodiesterases (PDEs) are a family of phosphohydrolyases that catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). PDEs regulate the second messengers by controlling their degradation.

Gene Wiki entry for PDE5A Gene

Additional gene information for PDE5A Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PDE5A Gene

Genomics for PDE5A Gene

GeneHancer (GH) Regulatory Elements for PDE5A Gene

Promoters and enhancers for PDE5A Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J119623 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.9 905 9.8 SIN3A ZNF2 ZNF48 ZNF121 GLIS2 ZNF207 ZNF143 FOS KLF13 SP3 LOC105377396 PDE5A GC04P119639 GC04M119628 LOC645513 USP53 FABP2 KLHL2P1 ENSG00000260091
GH04J119678 Promoter/Enhancer 1 EPDnew Ensembl ENCODE 650.2 -50.4 -50411 1.5 MAFK PDE5A LOC105377397
GH04J119653 Enhancer 0.7 ENCODE 11.9 -28.1 -28092 6.4 FOXA2 FEZF1 ZNF335 CTBP1 GATA3 PRDM10 RCOR1 FOS MAFK CHD2 LOC645513 USP53 PDE5A ENSG00000260091 KLHL2P1 LOC105377397
GH04J119681 Enhancer 0.7 ENCODE 10.7 -54.3 -54260 4 FOXA2 ZBTB21 MAX RAD21 YY1 GATA3 EGR1 HNF4G RXRA REST PDE5A LOC645513 LOC105377397
GH04J120006 Enhancer 1 Ensembl ENCODE 6.3 -379.1 -379079 2.3 PKNOX1 ZBTB21 INSM2 EBF1 FEZF1 BATF GATA3 ZNF366 ATF7 FOS PDE5A GC04P120002 ENSG00000253825
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PDE5A on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PDE5A gene promoter:
  • Cdc5
  • Nkx6-1
  • C/EBPalpha
  • C/EBPbeta

Genomic Locations for PDE5A Gene

Genomic Locations for PDE5A Gene
chr4:119,494,395-119,628,991
(GRCh38/hg38)
Size:
134,597 bases
Orientation:
Minus strand
chr4:120,415,550-120,550,146
(GRCh37/hg19)
Size:
134,597 bases
Orientation:
Minus strand

Genomic View for PDE5A Gene

Genes around PDE5A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDE5A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PDE5A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDE5A Gene

Proteins for PDE5A Gene

  • Protein details for PDE5A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O76074-PDE5A_HUMAN
    Recommended name:
    cGMP-specific 3,5-cyclic phosphodiesterase
    Protein Accession:
    O76074
    Secondary Accessions:
    • A0AV69
    • A8K2C4
    • O75026
    • O75887
    • Q86UI0
    • Q86V66
    • Q9Y6Z6

    Protein attributes for PDE5A Gene

    Size:
    875 amino acids
    Molecular mass:
    99985 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for PDE5A Gene

    Alternative splice isoforms for PDE5A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PDE5A Gene

Post-translational modifications for PDE5A Gene

  • Phosphorylation is regulated by binding of cGMP to the two allosteric sites (By similarity). Phosphorylation by PRKG1 leads to its activation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PDE5A Gene

No data available for DME Specific Peptides for PDE5A Gene

Domains & Families for PDE5A Gene

Gene Families for PDE5A Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry

O76074

UniProtKB/Swiss-Prot:

PDE5A_HUMAN :
  • Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.
  • Belongs to the cyclic nucleotide phosphodiesterase family.
Domain:
  • Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.
Family:
  • Belongs to the cyclic nucleotide phosphodiesterase family.
genes like me logo Genes that share domains with PDE5A: view

Function for PDE5A Gene

Molecular function for PDE5A Gene

UniProtKB/Swiss-Prot Function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
UniProtKB/Swiss-Prot CatalyticActivity:
Guanosine 3,5-cyclic phosphate + H(2)O = guanosine 5-phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast.
GENATLAS Biochemistry:
cGMP specific nucleotide phosphodiesterase,class V,alpha subunit,two alternatively spliced forms A1,A2,100kDa,highly expressed in tissues,aortic smooth muscle cells,heart,placenta,skeletal muscle,pancreas,brain,liver and lung

Enzyme Numbers (IUBMB) for PDE5A Gene

Phenotypes From GWAS Catalog for PDE5A Gene

Gene Ontology (GO) - Molecular Function for PDE5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004112 cyclic-nucleotide phosphodiesterase activity IEA --
GO:0004114 3,5-cyclic-nucleotide phosphodiesterase activity IEA,NAS 9714779
GO:0005515 protein binding IEA,IPI 18757735
GO:0008081 phosphoric diester hydrolase activity IEA --
genes like me logo Genes that share ontologies with PDE5A: view
genes like me logo Genes that share phenotypes with PDE5A: view

Animal Model Products

  • Taconic Biosciences Mouse Models for PDE5A

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PDE5A

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for PDE5A Gene

Localization for PDE5A Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PDE5A gene
Compartment Confidence
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PDE5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with PDE5A: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for PDE5A Gene

Pathways & Interactions for PDE5A Gene

genes like me logo Genes that share pathways with PDE5A: view

Pathways by source for PDE5A Gene

2 KEGG pathways for PDE5A Gene
1 GeneGo (Thomson Reuters) pathway for PDE5A Gene
1 Qiagen pathway for PDE5A Gene
1 Cell Signaling Technology pathway for PDE5A Gene

UniProtKB/Swiss-Prot O76074-PDE5A_HUMAN

  • Pathway: Purine metabolism; 3,5-cyclic GMP degradation; GMP from 3,5-cyclic GMP: step 1/1.

Gene Ontology (GO) - Biological Process for PDE5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0008152 metabolic process IEA --
GO:0010613 positive regulation of cardiac muscle hypertrophy IEA --
GO:0030823 regulation of cGMP metabolic process IEA --
GO:0042130 negative regulation of T cell proliferation IEA --
genes like me logo Genes that share ontologies with PDE5A: view

No data available for SIGNOR curated interactions for PDE5A Gene

Drugs & Compounds for PDE5A Gene

(72) Drugs for PDE5A Gene - From: DrugBank, DGIdb, FDA Approved Drugs, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sildenafil Approved, Investigational Pharma Inhibition, Inhibitor, inhibitor, Target PDE5 inhibitor, selective 0
Tadalafil Approved, Investigational Pharma inhibitor, Target PDE5 inhibitor 162
Vardenafil Approved Pharma binder, Target, inhibitor PDE5 inhibitor 0
Udenafil Approved, Investigational Pharma inhibitor, Target 34
Dipyridamole Approved Pharma Inhibition, Inhibitor, inhibitor, Target Adenosine transport inhibitor 84

(22) Additional Compounds for PDE5A Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
IBMX
Antagonist 28822-58-4
Eggmanone
505068-32-6
Etazolate hydrochloride
35838-58-5
MY-5445
78351-75-4
Ro 20-1724
29925-17-5

(5) Tocris Compounds for PDE5A Gene

Compound Action Cas Number
Eggmanone Potent and selective PDE4 inhibitor; suppresses hedgehog signaling 505068-32-6
Etazolate hydrochloride PDE4 inhibitor 35838-58-5
IBMX PDE inhibitor (non-selective) 28822-58-4
MY-5445 PDE5 inhibitor 78351-75-4
Ro 20-1724 PDE4 inhibitor 29925-17-5
genes like me logo Genes that share compounds with PDE5A: view

Transcripts for PDE5A Gene

mRNA/cDNA for PDE5A Gene

Unigene Clusters for PDE5A Gene

Phosphodiesterase 5A, cGMP-specific:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PDE5A

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PDE5A Gene

No ASD Table

Relevant External Links for PDE5A Gene

GeneLoc Exon Structure for
PDE5A
ECgene alternative splicing isoforms for
PDE5A

Expression for PDE5A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for PDE5A Gene

mRNA differential expression in normal tissues according to GTEx for PDE5A Gene

This gene is overexpressed in Artery - Aorta (x5.1), Artery - Tibial (x5.1), Esophagus - Muscularis (x4.5), and Esophagus - Gastroesophageal Junction (x4.4).

Protein differential expression in normal tissues from HIPED for PDE5A Gene

This gene is overexpressed in Peripheral blood mononuclear cells (44.9) and Platelet (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PDE5A Gene



Protein tissue co-expression partners for PDE5A Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of PDE5A Gene:

PDE5A

SOURCE GeneReport for Unigene cluster for PDE5A Gene:

Hs.647971

mRNA Expression by UniProt/SwissProt for PDE5A Gene:

O76074-PDE5A_HUMAN
Tissue specificity: Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung.

Evidence on tissue expression from TISSUES for PDE5A Gene

  • Muscle(4.6)
  • Nervous system(4.6)
  • Lung(4.5)
  • Eye(4.4)
  • Blood(3)
  • Heart(3)
  • Kidney(2)
genes like me logo Genes that share expression patterns with PDE5A: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for PDE5A Gene

Orthologs for PDE5A Gene

This gene was present in the common ancestor of animals.

Orthologs for PDE5A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PDE5A 34 33
  • 99.76 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PDE5A 34 33
  • 94.55 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PDE5A 34 33
  • 92.91 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PDE5A 34
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pde5a 33
  • 89.39 (n)
mouse
(Mus musculus)
Mammalia Pde5a 16 34 33
  • 88.79 (n)
oppossum
(Monodelphis domestica)
Mammalia PDE5A 34
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves PDE5A 34 33
  • 81.99 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PDE5A 34
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pde5a 33
  • 75.77 (n)
zebrafish
(Danio rerio)
Actinopterygii pde5ab 34 33
  • 70.14 (n)
ManyToMany
CT826376.1 34
  • 38 (a)
ManyToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6340 33
fruit fly
(Drosophila melanogaster)
Insecta Pde11 33
  • 54.04 (n)
CG10231 35
  • 48 (a)
CG8279 35
  • 44 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008646 33
  • 52.12 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 20 (a)
OneToMany
Species where no ortholog for PDE5A was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PDE5A Gene

ENSEMBL:
Gene Tree for PDE5A (if available)
TreeFam:
Gene Tree for PDE5A (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PDE5A: view image

Paralogs for PDE5A Gene

(9) SIMAP similar genes for PDE5A Gene using alignment to 9 proteins:

  • PDE5A_HUMAN
  • C9JGT3_HUMAN
  • G5E9C5_HUMAN
  • H0YA14_HUMAN
  • Q4W5L4_HUMAN
  • Q9P0K3_HUMAN
  • Q9P0K4_HUMAN
  • Q9P0K5_HUMAN
  • Q9P0K6_HUMAN
genes like me logo Genes that share paralogs with PDE5A: view

Variants for PDE5A Gene

Sequence variations from dbSNP and Humsavar for PDE5A Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs1000017588 -- 119,621,248(-) T/C intron_variant
rs1000035055 -- 119,590,029(-) T/C intron_variant
rs1000047520 -- 119,538,453(-) A/T intron_variant
rs1000047978 -- 119,569,900(-) C/G intron_variant
rs1000060342 -- 119,586,747(-) AATGTAATG/AATG intron_variant

Structural Variations from Database of Genomic Variants (DGV) for PDE5A Gene

Variant ID Type Subtype PubMed ID
esv2728237 CNV deletion 23290073
esv3601971 CNV gain 21293372
esv3601973 CNV gain 21293372
nsv1006572 CNV gain 25217958
nsv822710 CNV loss 20364138

Variation tolerance for PDE5A Gene

Residual Variation Intolerance Score: 77.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.31; 62.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PDE5A Gene

Human Gene Mutation Database (HGMD)
PDE5A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PDE5A

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDE5A Gene

Disorders for PDE5A Gene

MalaCards: The human disease database

(25) MalaCards diseases for PDE5A Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
priapism
  • priapism, familial idiopathic
nonarteritic anterior ischemic optic neuropathy
  • nonarteritic anterior ischemic optic neuropathy, susceptibility to
impotence
  • erectile dysfunction
transient global amnesia
  • amnesia, transient global
sexual disorder
  • sexual dysfunction
- elite association - COSMIC cancer census association via MalaCards
Search PDE5A in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PDE5A

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PDE5A: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PDE5A Gene

Publications for PDE5A Gene

  1. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. (PMID: 9714779) Loughney K … Ferguson K (Gene 1998) 2 3 4 22 58
  2. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (PMID: 12955149) Sung BJ … Cho JM (Nature 2003) 3 4 25 58
  3. Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). (PMID: 9642111) Stacey P … Phillips SC (Biochemical and biophysical research communications 1998) 2 3 4 58
  4. A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts. (PMID: 20332099) Kalsi G … Riley BP (Human molecular genetics 2010) 3 44 58
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 44 58

Products for PDE5A Gene

Sources for PDE5A Gene

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