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    ALDH1L1 aldehyde dehydrogenase 1 family member L1 [ Homo sapiens (human) ]

    Gene ID: 10840, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ALDH1L1provided by HGNC
    Official Full Name
    aldehyde dehydrogenase 1 family member L1provided by HGNC
    Primary source
    HGNC:HGNC:3978
    See related
    Ensembl:ENSG00000144908 MIM:600249; AllianceGenome:HGNC:3978
    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
    FDH; FTHFD; 10-fTHF; 10-FTHFDH
    Summary
    The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
    Expression
    Biased expression in liver (RPKM 99.3), kidney (RPKM 65.2) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ALDH1L1 in Genome Data Viewer
    Location:
    3q21.3
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (126103570..126197945, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (128835963..128930120, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (125822413..125900029, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ALG1 like 1, pseudogene Neighboring gene rhophilin associated tail protein 1B Neighboring gene ReSE screen-validated silencer GRCh37_chr3:125736296-125736478 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr3:125740258-125741040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125744116-125744616 Neighboring gene solute carrier family 41 member 3 Neighboring gene uncharacterized LOC124909425 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125777675-125778174 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14672 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14673 Neighboring gene ALDH1L1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20436 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125822083-125822904 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125831607-125832121 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125847779-125848549 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125850681-125851498 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14674 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125855703-125856203 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_64577 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125876969-125877469 Neighboring gene uncharacterized LOC105374083 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125899089-125899844 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125899845-125900598 Neighboring gene RNA, U1 small nuclear 30, pseudogene Neighboring gene Sharpr-MPRA regulatory region 2719 Neighboring gene ALDH1L1 antisense RNA 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20437 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:125926972-125928171 Neighboring gene uncharacterized LOC124909426 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125932350-125932862 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125977069-125977976 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:125985551-125986260 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:125986261-125986971 Neighboring gene uncharacterized LOC107986124 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:126006839-126007384 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:126007385-126007929 Neighboring gene KLF transcription factor 15

    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 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. Conserved catalytic residues of the ALDH1L1 aldehyde dehydrogenase domain control binding and discharging of the coenzyme. Tsybovsky Y, et al. J Biol Chem, 2011 Jul 1. PMID 21540484, Free PMC Article
    2. Modeling of interactions between functional domains of ALDH1L1. Horita DA, et al. Chem Biol Interact, 2017 Oct 1. PMID 28414156, Free PMC Article
    3. Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion. Kang JH, et al. Oncotarget, 2016 Aug 2. PMID 27384481, Free PMC Article
    4. Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population. Wu L, et al. Neurol Sci, 2016 Jul. PMID 26993122
    5. Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation? Brosnan ME, et al. Biochem J, 2015 Dec 1. PMID 26567272

    See all (84) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression.
      Title: One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression.
    2. Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.
      Title: Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.
    3. Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.
      Title: Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.
    4. [Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer].
      Title: [Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer].
    5. Our results suggest that ALDH1L1 may be a biomarker for predicting postoperative clinical outcomes. Moreover, ALDH1L1-rs2276724 and mRNA expression were associated with TP53 expression in HBV-related hepatocellular carcinoma patients
      Title: ALDH1L1 variant rs2276724 and mRNA expression predict post-operative clinical outcomes and are associated with TP53 expression in HBV-related hepatocellular carcinoma.
    6. ALDH1L1 has a role in response to the combined treatment of gossypol and phenformin in non-small cell lung cancer
      Title: Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion.
    7. high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in gastric cancer patients
      Title: Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.
    8. The three functional domains of ALDH1L1 was defined positions of the 4'-phosphopantetheine arm within the two catalytic domains and to predict N-terminal:intermediate and intermediate:C-terminal domain interfaces.
      Title: Modeling of interactions between functional domains of ALDH1L1.
    9. The polymorphic loci rs4646733, rs2305225, and rs2276731 in the ALDH1L1 gene maybe potential risk factors for neural tube defects in the Chinese population.
      Title: Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population.
    10. Data suggest that isoforms of FTHFD occur both in mitochondria and in cytosol; activity of cytosolic FTHFD appears to respond to supply of one-carbon groups in excess of those required for classical one-carbon metabolism. [REVIEW]
      Title: Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    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
    Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
    EBI GWAS Catalog
    Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
    EBI GWAS Catalog
    Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke.
    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)

    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

    • DKFZp781N0997

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aldehyde dehydrogenase (NAD+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables formyltetrahydrofolate dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables formyltetrahydrofolate dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables formyltetrahydrofolate dehydrogenase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in 10-formyltetrahydrofolate catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in 10-formyltetrahydrofolate catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in NADPH regeneration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in one-carbon metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in mitochondrion HTP PubMed 

    General protein information

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    Preferred Names
    cytosolic 10-formyltetrahydrofolate dehydrogenase
    Names
    10-formyltetrahydrofolate dehydrogenase
    MER57B-ALDH1L1
    NP_001257293.1
    NP_001257294.1
    NP_036322.2
    XP_006713544.1
    XP_011510657.1
    XP_016861102.1
    XP_016861103.1
    XP_024309093.1
    XP_054201003.1
    XP_054201004.1
    XP_054201005.1
    XP_054201006.1
    XP_054201007.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_012260.2 RefSeqGene

      Range
      22359..99375
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001270364.2 → NP_001257293.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 1

      See identical proteins and their annotated locations for NP_001257293.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest protein (isoform 1).
      Source sequence(s)
      AC079848
      Consensus CDS
      CCDS58851.1
      UniProtKB/TrEMBL
      Q53H87
      Related
      ENSP00000273450.3, ENST00000273450.7
      Conserved Domains (5) summary
      cd07140
      Location:427 → 912
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08647
      Location:11 → 213
      FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
      cd08703
      Location:216 → 316
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      COG0223
      Location:10 → 319
      Fmt; Methionyl-tRNA formyltransferase [Translation, ribosomal structure and biogenesis]
      pfam00550
      Location:335 → 401
      PP-binding; Phosphopantetheine attachment site

    2. NM_001270365.2 → NP_001257294.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the both the 5' UTR and the coding sequence, but maintains the reading frame, compared to variant 1. The resulting isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC079848, AK222694, AK294392
      Consensus CDS
      CCDS58850.1
      UniProtKB/TrEMBL
      Q53H87
      Related
      ENSP00000395881.2, ENST00000452905.6
      Conserved Domains (4) summary
      cd07140
      Location:316 → 801
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08703
      Location:116 → 205
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      pfam00550
      Location:224 → 290
      PP-binding; Phosphopantetheine attachment site
      cl00395
      Location:1 → 128
      FMT_core; Formyltransferase, catalytic core domain

    3. NM_012190.4 → NP_036322.2  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 2

      See identical proteins and their annotated locations for NP_036322.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains a distinct 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at an alternate in-frame downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC079848, AF052732, AK222694, DC342268
      Consensus CDS
      CCDS3034.1
      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
      UniProtKB/TrEMBL
      Q53H87
      Related
      ENSP00000377083.3, ENST00000393434.7
      Conserved Domains (4) summary
      cd07140
      Location:417 → 902
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08647
      Location:1 → 203
      FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
      cd08703
      Location:206 → 306
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      pfam00550
      Location:325 → 391
      PP-binding; Phosphopantetheine attachment site

    RNA

    1. NR_072979.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK222694, BC027241, DC342268
      Related
      ENST00000393431.6

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      126103570..126197945 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024453325.2 → XP_024309093.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
      UniProtKB/TrEMBL
      Q53H87
      Conserved Domains (4) summary
      cd07140
      Location:417 → 902
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08647
      Location:1 → 203
      FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
      cd08703
      Location:206 → 306
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      pfam00550
      Location:325 → 391
      PP-binding; Phosphopantetheine attachment site

    2. XM_011512355.2 → XP_011510657.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      See identical proteins and their annotated locations for XP_011510657.1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
      UniProtKB/TrEMBL
      Q53H87
      Related
      ENSP00000420293.1, ENST00000472186.5
      Conserved Domains (4) summary
      cd07140
      Location:417 → 902
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08647
      Location:1 → 203
      FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
      cd08703
      Location:206 → 306
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      pfam00550
      Location:325 → 391
      PP-binding; Phosphopantetheine attachment site

    3. XM_017005613.3 → XP_016861102.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X2

      UniProtKB/TrEMBL
      Q53H87

    4. XM_006713481.4 → XP_006713544.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      See identical proteins and their annotated locations for XP_006713544.1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
      UniProtKB/TrEMBL
      Q53H87
      Conserved Domains (4) summary
      cd07140
      Location:417 → 902
      ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
      cd08647
      Location:1 → 203
      FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
      cd08703
      Location:206 → 306
      FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
      pfam00550
      Location:325 → 391
      PP-binding; Phosphopantetheine attachment site

    5. XM_017005614.3 → XP_016861103.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X3

      UniProtKB/TrEMBL
      Q53H87

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      128835963..128930120 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054345030.1 → XP_054201005.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

    2. XM_054345029.1 → XP_054201004.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

    3. XM_054345031.1 → XP_054201006.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X2

    4. XM_054345028.1 → XP_054201003.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

      UniProtKB/Swiss-Prot
      B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

    5. XM_054345032.1 → XP_054201007.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_144776.1: Suppressed sequence

      Description
      NM_144776.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75891.2 GenPept UniProtKB/Swiss-Prot:O75891

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