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    FLRT2 fibronectin leucine rich transmembrane protein 2 [ Homo sapiens (human) ]

    Gene ID: 23768, updated on 9-Dec-2024

    Summary

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    Official Symbol
    FLRT2provided by HGNC
    Official Full Name
    fibronectin leucine rich transmembrane protein 2provided by HGNC
    Primary source
    HGNC:HGNC:3761
    See related
    Ensembl:ENSG00000185070 MIM:604807; AllianceGenome:HGNC:3761
    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
    Summary
    This gene encodes a member of the fibronectin leucine rich transmembrane (FLRT) family of cell adhesion molecules, which regulate early embryonic vascular and neural development. The encoded type I transmembrane protein has an extracellular region consisting of an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, followed by a transmembrane domain and a short C-terminal cytoplasmic tail domain. It functions as both a homophilic cell adhesion molecule and a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. Proteolytic removal of the extracellular region controls the migration of neurons in the developing cortex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
    Expression
    Ubiquitous expression in ovary (RPKM 6.8), brain (RPKM 2.7) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FLRT2 in Genome Data Viewer
    Location:
    14q31.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (85530144..85654428)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (79742250..79868256)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (85996488..86120772)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2329 Neighboring gene long intergenic non-protein coding RNA 911 Neighboring gene FLRT2 antisense RNA 1 Neighboring gene NANOG hESC enhancer GRCh37_chr14:86035212-86035730 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:86041781-86042407 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38044 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38047 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38246 Neighboring gene NANOG hESC enhancer GRCh37_chr14:86342091-86342659 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8832 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8831 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38309 Neighboring gene long intergenic non-protein coding RNA 2328 Neighboring gene long intergenic non-protein coding RNA 2316 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38386 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:86545921-86546560 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:86546561-86547199 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:86567507-86568008 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:86582175-86582676 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38415 Neighboring gene Sharpr-MPRA regulatory region 9105 Neighboring gene long intergenic non-protein coding RNA 2309

    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. FLRT2 suppresses bladder cancer progression through inducing ferroptosis. Jiang P, et al. J Cell Mol Med, 2024 Mar. PMID 37480224, Free PMC Article
    2. A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus. Shirai T, et al. Arthritis Res Ther, 2012 Jul 2. PMID 22747982, Free PMC Article
    3. Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells. Bae H, et al. Sci Rep, 2017 Mar 21. PMID 28325946, Free PMC Article
    4. Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer. Wu Y, et al. Epigenetics, 2016 Apr 2. PMID 26890304, Free PMC Article
    5. FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway. Hwang HJ, et al. JCI Insight, 2024 Apr 8. PMID 38587072, Free PMC Article

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. FLRT2 suppresses bladder cancer progression through inducing ferroptosis.
      Title: FLRT2 suppresses bladder cancer progression through inducing ferroptosis.
    2. FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
      Title: FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
    3. Taken together, these results provide insights into the role of FLRT2 as a novel tumor suppressor in the breast, which is inactivated by hypermethylation during tumor development.
      Title: Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells.
    4. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci
      Title: Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.
    5. The membrane protein, FLRT2, was identified as a novel autoantigen in systemic lupus erythematosus patients.
      Title: A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus.
    6. PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe Obstructive sleep apnea in Asian populations
      Title: Gene expression profiles in peripheral blood mononuclear cells of Asian obstructive sleep apnea patients.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.
    Submit: New GeneRIF Correction

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
    EBI GWAS Catalog
    Genome-wide association study of age at menarche in African-American women.
    EBI GWAS Catalog
    Genome-wide association study of lung function decline in adults with and without asthma.
    EBI GWAS Catalog
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ51243, KIAA0405

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables chemorepellent activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables fibroblast growth factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein-macromolecule adaptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in axon guidance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in basement membrane organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cell adhesion involved in heart morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in fibroblast growth factor receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in heart morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative chemotaxis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of synapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of neuron migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cell-cell junction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in focal adhesion HDA PubMed 
    colocalizes_with focal adhesion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in neuron projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    leucine-rich repeat transmembrane protein FLRT2
    Names
    fibronectin-like domain-containing leucine-rich transmembrane protein 2

    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.

    mRNA and Protein(s)

    1. NM_001346143.2 → NP_001333072.1  leucine-rich repeat transmembrane protein FLRT2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL049775, AL132641
      Consensus CDS
      CCDS9877.1
      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
      Related
      ENSP00000507815.1, ENST00000683129.1
      Conserved Domains (7) summary
      TIGR00864
      Location:282 → 359
      PCC; polycystin cation channel protein
      smart00013
      Location:35 → 66
      LRRNT; Leucine rich repeat N-terminal domain
      sd00031
      Location:65 → 86
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:90 → 110
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00041
      Location:426 → 494
      fn3; Fibronectin type III domain
      pfam13855
      Location:252 → 311
      LRR_8; Leucine rich repeat
      cl26018
      Location:54 → 265
      NEL; C-terminal novel E3 ligase, LRR-interacting

    2. NM_001346144.2 → NP_001333073.1  leucine-rich repeat transmembrane protein FLRT2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL049775, AL132641
      Consensus CDS
      CCDS9877.1
      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
      Related
      ENSP00000451050.1, ENST00000554746.1
      Conserved Domains (7) summary
      TIGR00864
      Location:282 → 359
      PCC; polycystin cation channel protein
      smart00013
      Location:35 → 66
      LRRNT; Leucine rich repeat N-terminal domain
      sd00031
      Location:65 → 86
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:90 → 110
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00041
      Location:426 → 494
      fn3; Fibronectin type III domain
      pfam13855
      Location:252 → 311
      LRR_8; Leucine rich repeat
      cl26018
      Location:54 → 265
      NEL; C-terminal novel E3 ligase, LRR-interacting

    3. NM_001346145.2 → NP_001333074.1  leucine-rich repeat transmembrane protein FLRT2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL049775, AL132641
      Consensus CDS
      CCDS9877.1
      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
      Conserved Domains (7) summary
      TIGR00864
      Location:282 → 359
      PCC; polycystin cation channel protein
      smart00013
      Location:35 → 66
      LRRNT; Leucine rich repeat N-terminal domain
      sd00031
      Location:65 → 86
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:90 → 110
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00041
      Location:426 → 494
      fn3; Fibronectin type III domain
      pfam13855
      Location:252 → 311
      LRR_8; Leucine rich repeat
      cl26018
      Location:54 → 265
      NEL; C-terminal novel E3 ligase, LRR-interacting

    4. NM_001346146.2 → NP_001333075.1  leucine-rich repeat transmembrane protein FLRT2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL049775, AL132641
      Consensus CDS
      CCDS9877.1
      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
      Related
      ENSP00000507088.1, ENST00000682132.1
      Conserved Domains (7) summary
      TIGR00864
      Location:282 → 359
      PCC; polycystin cation channel protein
      smart00013
      Location:35 → 66
      LRRNT; Leucine rich repeat N-terminal domain
      sd00031
      Location:65 → 86
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:90 → 110
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00041
      Location:426 → 494
      fn3; Fibronectin type III domain
      pfam13855
      Location:252 → 311
      LRR_8; Leucine rich repeat
      cl26018
      Location:54 → 265
      NEL; C-terminal novel E3 ligase, LRR-interacting

    5. NM_013231.6 → NP_037363.1  leucine-rich repeat transmembrane protein FLRT2 precursor

      See identical proteins and their annotated locations for NP_037363.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL049775, AL132641
      Consensus CDS
      CCDS9877.1
      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
      Related
      ENSP00000332879.4, ENST00000330753.6
      Conserved Domains (7) summary
      TIGR00864
      Location:282 → 359
      PCC; polycystin cation channel protein
      smart00013
      Location:35 → 66
      LRRNT; Leucine rich repeat N-terminal domain
      sd00031
      Location:65 → 86
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:90 → 110
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00041
      Location:426 → 494
      fn3; Fibronectin type III domain
      pfam13855
      Location:252 → 311
      LRR_8; Leucine rich repeat
      cl26018
      Location:54 → 265
      NEL; C-terminal novel E3 ligase, LRR-interacting

    RNA

    1. NR_144385.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains the same first exon but uses an alternate 3' exon structure, compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
      Source sequence(s)
      AL049775, BX119446

    2. NR_144386.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) uses an alternate exon structure compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
      Source sequence(s)
      AL049775, BX119446

    3. NR_144387.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses an alternate exon structure compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
      Source sequence(s)
      AL049775, BX119446
      Related
      ENST00000557419.5

    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_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      85530144..85654428
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431176.1 → XP_047287132.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      79742250..79868256
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_060077468.1 → XP_059933451.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    2. XM_060077469.1 → XP_059933452.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    3. XM_060077472.1 → XP_059933455.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    4. XM_060077471.1 → XP_059933454.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    5. XM_060077466.1 → XP_059933449.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    6. XM_060077470.1 → XP_059933453.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    7. XM_047446351.1 → XP_047302307.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    8. XM_047446350.1 → XP_047302306.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    9. XM_060077467.1 → XP_059933450.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    10. XM_060077473.1 → XP_059933456.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    11. XM_060077465.1 → XP_059933448.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2

    12. XM_047446352.1 → XP_047302308.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

      UniProtKB/Swiss-Prot
      A0AV84, B7ZLP3, O43155
      UniProtKB/TrEMBL
      B3KPR2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43155.1 GenPept UniProtKB/Swiss-Prot:O43155

    Gene LinkOut

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