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    SCN3A sodium voltage-gated channel alpha subunit 3 [ Homo sapiens (human) ]

    Gene ID: 6328, updated on 27-Nov-2024

    Summary

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    Official Symbol
    SCN3Aprovided by HGNC
    Official Full Name
    sodium voltage-gated channel alpha subunit 3provided by HGNC
    Primary source
    HGNC:HGNC:10590
    See related
    Ensembl:ENSG00000153253 MIM:182391; AllianceGenome:HGNC:10590
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NAC3; DEE62; EIEE62; FFEVF4; Nav1.3
    Summary
    Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is found in a cluster of five alpha subunit genes on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in brain (RPKM 5.7), adrenal (RPKM 1.1) and 11 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SCN3A in Genome Data Viewer
    Location:
    2q24.3
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (165087526..165204050, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (165544858..165661382, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (165944036..166060560, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 110 Neighboring gene NANOG hESC enhancer GRCh37_chr2:165769454-165769970 Neighboring gene RNA, 5S ribosomal pseudogene 111 Neighboring gene solute carrier family 38 member 11 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:165840567-165840754 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165851409-165851909 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165926349-165926850 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:165926851-165927350 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12066 Neighboring gene Sharpr-MPRA regulatory region 13511 Neighboring gene sodium voltage-gated channel alpha subunit 2 Neighboring gene MAPRE1 pseudogene 3 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:166279515-166280129 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:166283004-166283939 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:166317128-166318327 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166385525-166386157 Neighboring gene cysteine and serine rich nuclear protein 3 Neighboring gene MPRA-validated peak3912 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr2:166436961-166437478 Neighboring gene NANOG hESC enhancer GRCh37_chr2:166437479-166437996 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16726 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16727 Neighboring gene uncharacterized LOC124906085 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166490986-166491565 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:166491566-166492144

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy. Qu G, et al. Brain, 2024 Apr 4. PMID 37935051, Free PMC Article
    2. Mutations in SCN3A cause early infantile epileptic encephalopathy. Zaman T, et al. Ann Neurol, 2018 Apr. PMID 29466837, Free PMC Article
    3. Novel SCN3A variants associated with focal epilepsy in children. Vanoye CG, et al. Neurobiol Dis, 2014 Feb. PMID 24157691, Free PMC Article
    4. Upregulated expression of voltage-gated sodium channel Nav1.3 in cortical lesions of patients with focal cortical dysplasia type IIb. Yu S, et al. Neuroreport, 2012 May 9. PMID 22494998
    5. Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development. Smith RS, et al. Neuron, 2018 Sep 5. PMID 30146301, Free PMC Article

    See all (49) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Neurodevelopmental disorder in a patient with HMBS and SCN3A variants-A possibly blended phenotype further delineating autosomal recessive HMBS related disease.
      Title: Neurodevelopmental disorder in a patient with HMBS and SCN3A variants-A possibly blended phenotype further delineating autosomal recessive HMBS related disease.
    2. Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy.
      Title: Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy.
    3. Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
      Title: Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
    4. Mutations in the sodium channel genes SCN1A, SCN3A, and SCN9A in children with epilepsy with febrile seizures plus(EFS+).
      Title: Mutations in the sodium channel genes SCN1A, SCN3A, and SCN9A in children with epilepsy with febrile seizures plus(EFS+).
    5. SCN3A-Related Neurodevelopmental Disorder: A Spectrum of Epilepsy and Brain Malformation.
      Title: SCN3A-Related Neurodevelopmental Disorder: A Spectrum of Epilepsy and Brain Malformation.
    6. Long noncoding RNA HOXA-AS2 regulates the expression of SCN3A by sponging miR-106a in breast cancer.
      Title: Long noncoding RNA HOXA-AS2 regulates the expression of SCN3A by sponging miR-106a in breast cancer.
    7. SCN3A expression is involved in the prenatal development of human cortical language areas.
      Title: Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development.
    8. The findings of this study established SCN3A as a new gene for infantile epileptic encephalopathy and suggest a potential pharmacologic intervention.
      Title: Mutations in SCN3A cause early infantile epileptic encephalopathy.
    9. Study represents the first evidence of the abnormal changes in voltage-gated sodium channels subtypes (including Nav1.3) and CaM/CaMKII pathway in human brain low-grade astrocytoma, providing new potential targets for molecular therapies of this disease.
      Title: Abnormal changes in voltage-gated sodium channels subtypes Na(V)1.1, Na(V)1.2, Na(V)1.3, Na(V)1.6 and CaM/CaMKII pathway in low-grade astrocytoma.
    10. SCN3A is involved in development of the human brain and oral motor development. When SCN3A is mutated, patients present with polymicrogyria and speech deficits.
      Title: Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif downregulates the expression of sodium channel, voltage-gated, type III, alpha subunit (SCN3A) in Vif-expression T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA1356

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables voltage-gated sodium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables voltage-gated sodium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in behavioral response to pain IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cardiac muscle cell action potential involved in contraction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in membrane depolarization during action potential IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sodium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sodium ion transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in basal plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in sarcoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of voltage-gated sodium channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of voltage-gated sodium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sodium channel protein type 3 subunit alpha
    Names
    brain III voltage-gated sodium channel
    sodium channel protein brain III subunit alpha
    sodium channel protein type III subunit alpha
    sodium channel, voltage gated, type III alpha subunit
    sodium channel, voltage-gated, type III, alpha polypeptide
    voltage-gated sodium channel subtype III
    voltage-gated sodium channel subunit alpha Nav1.3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_042289.1 RefSeqGene

      Range
      5039..121563
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001081676.2 → NP_001075145.1  sodium channel protein type 3 subunit alpha isoform 2

      See identical proteins and their annotated locations for NP_001075145.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as 12v1, SCN3A-s, or the adult form, uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in a shorter protein (isoform 2).
      Source sequence(s)
      AC013463, AF035686, AF225986, AJ251507, AL079365, BM681920, DA796981
      UniProtKB/TrEMBL
      Q9C007
      Conserved Domains (6) summary
      cd13433
      Location:1420 → 1472
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1174 → 1428
      Ion_trans; Ion transport protein
      pfam06512
      Location:949 → 1151
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 648
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1744 → 1799
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1659 → 1694
      ChtBD1; Hevein or type 1 chitin binding domain

    2. NM_001081677.2 → NP_001075146.1  sodium channel protein type 3 subunit alpha isoform 3

      See identical proteins and their annotated locations for NP_001075146.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as the neonatal form, uses an alternate in-frame splice site in the central coding region and an alternate form of an exon in the 5' coding region, compared to variant 1. The resulting isoform (3) is shorter than isoform 1, and contains one amino acid substitution relative to isoform 2.
      Source sequence(s)
      AC013463, AF035686, AJ251507, AL079365, BM681920, DA772987
      Consensus CDS
      CCDS46440.1
      UniProtKB/TrEMBL
      Q9C007
      Related
      ENSP00000386726.3, ENST00000409101.7
      Conserved Domains (6) summary
      cd13433
      Location:1420 → 1472
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1174 → 1428
      Ion_trans; Ion transport protein
      pfam06512
      Location:949 → 1151
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 648
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1744 → 1799
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1659 → 1694
      ChtBD1; Hevein or type 1 chitin binding domain

    3. NM_006922.4 → NP_008853.3  sodium channel protein type 3 subunit alpha isoform 1

      See identical proteins and their annotated locations for NP_008853.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as 12v4, represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC013463, AF035686, AF225987, AJ251507, AL079365, BM681920, DA796981
      Consensus CDS
      CCDS33312.1
      UniProtKB/TrEMBL
      A0A1W2PRD1
      Related
      ENSP00000283254.7, ENST00000283254.12
      Conserved Domains (6) summary
      cd13433
      Location:1469 → 1521
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1223 → 1477
      Ion_trans; Ion transport protein
      pfam06512
      Location:998 → 1200
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 629
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1793 → 1848
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1708 → 1743
      ChtBD1; Hevein or type 1 chitin binding domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      165087526..165204050 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017004662.3 → XP_016860151.1  sodium channel protein type 3 subunit alpha isoform X5

      UniProtKB/TrEMBL
      Q9C007

    2. XM_017004661.3 → XP_016860150.1  sodium channel protein type 3 subunit alpha isoform X3

      UniProtKB/TrEMBL
      A0A1W2PRD1
      Related
      ENSP00000492251.1, ENST00000639244.1
      Conserved Domains (6) summary
      cd13433
      Location:1452 → 1504
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1206 → 1460
      Ion_trans; Ion transport protein
      pfam06512
      Location:981 → 1183
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 629
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1776 → 1831
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1691 → 1726
      ChtBD1; Hevein or type 1 chitin binding domain

    3. XM_047445394.1 → XP_047301350.1  sodium channel protein type 3 subunit alpha isoform X4

      UniProtKB/TrEMBL
      A0A994J5P2
      Related
      ENSP00000516211.1, ENST00000706067.1

    4. XM_017004660.3 → XP_016860149.1  sodium channel protein type 3 subunit alpha isoform X1

      UniProtKB/Swiss-Prot
      Q16142, Q53SX0, Q9BZB3, Q9C006, Q9NY46, Q9NYK2, Q9P2J1, Q9UPD1, Q9Y6P4
      UniProtKB/TrEMBL
      A0A1W2PRD1
      Conserved Domains (6) summary
      cd13433
      Location:1469 → 1521
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1223 → 1477
      Ion_trans; Ion transport protein
      pfam06512
      Location:998 → 1200
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 629
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1793 → 1848
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1708 → 1743
      ChtBD1; Hevein or type 1 chitin binding domain

    5. XM_011511610.4 → XP_011509912.1  sodium channel protein type 3 subunit alpha isoform X2

      See identical proteins and their annotated locations for XP_011509912.1

      UniProtKB/TrEMBL
      A0A1W2PRD1
      Conserved Domains (6) summary
      cd13433
      Location:1469 → 1521
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:1223 → 1477
      Ion_trans; Ion transport protein
      pfam06512
      Location:998 → 1200
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 629
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel
      pfam16905
      Location:1793 → 1848
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1708 → 1743
      ChtBD1; Hevein or type 1 chitin binding domain

    6. XM_011511613.4 → XP_011509915.1  sodium channel protein type 3 subunit alpha isoform X6

      Conserved Domains (5) summary
      cd13433
      Location:839 → 891
      Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits
      pfam00520
      Location:593 → 847
      Ion_trans; Ion transport protein
      pfam06512
      Location:368 → 570
      Na_trans_assoc; Sodium ion transport-associated
      pfam16905
      Location:1163 → 1218
      GPHH; Voltage-dependent L-type calcium channel, IQ-associated
      cl16916
      Location:1078 → 1113
      ChtBD1; Hevein or type 1 chitin binding domain

    7. XM_047445395.1 → XP_047301351.1  sodium channel protein type 3 subunit alpha isoform X7

      Related
      ENSP00000403348.1, ENST00000440431.6

    8. XM_017004666.2 → XP_016860155.1  sodium channel protein type 3 subunit alpha isoform X10

      UniProtKB/TrEMBL
      A0A1W2PSB2

    9. XM_017004665.2 → XP_016860154.1  sodium channel protein type 3 subunit alpha isoform X9

      UniProtKB/TrEMBL
      A0A1W2PSB2, A0A590UJH3
      Related
      ENSP00000499420.1, ENST00000668657.1

    10. XM_017004664.2 → XP_016860153.1  sodium channel protein type 3 subunit alpha isoform X8

      UniProtKB/TrEMBL
      A0A1W2PSB2
      Related
      ENSP00000492807.1, ENST00000640652.1
      Conserved Domains (3) summary
      pfam00520
      Location:143 → 434
      Ion_trans; Ion transport protein
      pfam06512
      Location:998 → 1117
      Na_trans_assoc; Sodium ion transport-associated
      pfam11933
      Location:510 → 629
      Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      165544858..165661382 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343307.1 → XP_054199282.1  sodium channel protein type 3 subunit alpha isoform X5

    2. XM_054343305.1 → XP_054199280.1  sodium channel protein type 3 subunit alpha isoform X3

    3. XM_054343306.1 → XP_054199281.1  sodium channel protein type 3 subunit alpha isoform X4

      UniProtKB/TrEMBL
      A0A994J5P2

    4. XM_054343303.1 → XP_054199278.1  sodium channel protein type 3 subunit alpha isoform X1

      UniProtKB/Swiss-Prot
      Q16142, Q53SX0, Q9BZB3, Q9C006, Q9NY46, Q9NYK2, Q9P2J1, Q9UPD1, Q9Y6P4

    5. XM_054343304.1 → XP_054199279.1  sodium channel protein type 3 subunit alpha isoform X2

    6. XM_054343308.1 → XP_054199283.1  sodium channel protein type 3 subunit alpha isoform X6

    7. XM_054343309.1 → XP_054199284.1  sodium channel protein type 3 subunit alpha isoform X7

    8. XM_054343312.1 → XP_054199287.1  sodium channel protein type 3 subunit alpha isoform X10

    9. XM_054343311.1 → XP_054199286.1  sodium channel protein type 3 subunit alpha isoform X9

      UniProtKB/TrEMBL
      A0A590UJH3

    10. XM_054343310.1 → XP_054199285.1  sodium channel protein type 3 subunit alpha isoform X8

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NY46.2 GenPept UniProtKB/Swiss-Prot:Q9NY46

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