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TNFRSF11A TNF receptor superfamily member 11a [ Homo sapiens (human) ]

Gene ID: 8792, updated on 6-Jul-2026
Official Symbol
TNFRSF11Aprovided by HGNC
Official Full Name
TNF receptor superfamily member 11aprovided by HGNC
Primary source
HGNC:HGNC:11908
See related
Ensembl:ENSG00000141655 MIM:603499; AllianceGenome:HGNC:11908
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
FEO; OFE; ODFR; OSTS; PDB2; RANK; CD265; OPTB7; TRANCER; LOH18CR1; TRANCE-R
Summary
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]
Expression
Biased expression in duodenum (RPKM 14.3), colon (RPKM 11.6) and 10 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See TNFRSF11A in Genome Data Viewer
Location:
18q21.33
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (62325310..62391288)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (62528176..62594158)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (59992543..60058521)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 1275 Neighboring gene phosphatidylinositol glycan anchor biosynthesis class N Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48670 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48690 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48726/48728 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48738 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48746 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:59853791-59854003 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13429 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9502 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48887 Neighboring gene RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9503 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48897 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:59957531-59957709 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9504 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9505 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr18:60034196-60034732 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9506 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr18:60041621-60042250 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13430 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9507 Neighboring gene ribosomal protein L17 pseudogene 44 Neighboring gene ACTB pseudogene 9

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Langerhans cell precursors acquire RANK/CD265 in prenatal human skin. Schöppl A, et al. Acta Histochem, 2015 May-Jun. PMID 25722033, Free PMC Article
  2. RANK is expressed in metastatic melanoma and highly upregulated on melanoma-initiating cells. Kupas V, et al. J Invest Dermatol, 2011 Apr. PMID 21270824
  3. Evidence for a link between TNFRSF11A and risk of breast cancer. Bonifaci N, et al. Breast Cancer Res Treat, 2011 Oct. PMID 21541702
  4. RANK-dependent autosomal recessive osteopetrosis: characterization of five new cases with novel mutations. Pangrazio A, et al. J Bone Miner Res, 2012 Feb. PMID 22271396, Free PMC Article
  5. RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Palafox M, et al. Cancer Res, 2012 Jun 1. PMID 22496457

See all (293) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.
    Title: Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.
  2. B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.
    Title: B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.
  3. TNFRSF11A variants contribute to systemic autoinflammatory diseases: A case series of 12 patients.
    Title: TNFRSF11A variants contribute to systemic autoinflammatory diseases: A case series of 12 patients.
  4. Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).
    Title: Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).
  5. Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial.
    Title: Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial.
  6. The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.
    Title: The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.
  7. The Effect of Osteoprotectin (OPG)/Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL)/Receptor Activator of Nuclear Factor-kappaB (RANK) Gene Methylation on Aortic Valve Calcified.
    Title: The Effect of Osteoprotectin (OPG)/Receptor Activator of Nuclear Factor-κB Ligand (RANKL)/Receptor Activator of Nuclear Factor-κB (RANK) Gene Methylation on Aortic Valve Calcified.
  8. Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.
    Title: Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.
  9. RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages.
    Title: RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages.
  10. Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.
    Title: Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.
Submit: New GeneRIF Correction See all GeneRIFs (235)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Autosomal recessive osteopetrosis 7
MedGen: C2676766 OMIM: 612301 GeneReviews: Not available
not available
Familial expansile osteolysis
MedGen: C0432292 OMIM: 174810 GeneReviews: Not available
not available
Paget disease of bone 2, early-onset
MedGen: C4085251 OMIM: 602080 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Discovery and fine mapping of serum protein loci through transethnic meta-analysis.
EBI GWAS Catalog
Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.
EBI GWAS Catalog
Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.
EBI GWAS Catalog
Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.
EBI GWAS Catalog
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
EBI GWAS Catalog
Multiple genetic loci for bone mineral density and fractures.
EBI GWAS Catalog
Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
EBI GWAS Catalog
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytokine binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cytokine binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor activity TAS
Traceable Author Statement
more info
 PubMed 
enables transmembrane signaling receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transmembrane signaling receptor activity IEA
Inferred from Electronic Annotation
more info
  
enables tumor necrosis factor receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables tumor necrosis factor receptor activity IEA
Inferred from Electronic Annotation
more info
  
enables tumor necrosis factor receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
Process Evidence Code Pubs
involved_in adaptive immune response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to zinc ion starvation IEA
Inferred from Electronic Annotation
more info
  
involved_in circadian temperature homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in circadian temperature homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in immune system process IEA
Inferred from Electronic Annotation
more info
  
involved_in monocyte chemotaxis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in multinuclear osteoclast differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ossification IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in osteoclast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in osteoclast differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JNK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of bone resorption IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of canonical NF-kappaB signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of fever generation by positive regulation of prostaglandin secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of fever generation by positive regulation of prostaglandin secretion ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in positive regulation of non-canonical NF-kappaB signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of osteoclast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of osteoclast differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to ethanol IEA
Inferred from Electronic Annotation
more info
  
involved_in response to insulin IEA
Inferred from Electronic Annotation
more info
  
involved_in response to interleukin-1 IEA
Inferred from Electronic Annotation
more info
  
involved_in response to interleukin-1 ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in response to lipopolysaccharide IEA
Inferred from Electronic Annotation
more info
  
involved_in response to lipopolysaccharide ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in response to mechanical stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in response to tumor necrosis factor IEA
Inferred from Electronic Annotation
more info
  
involved_in response to tumor necrosis factor ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in tumor necrosis factor-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tumor necrosis factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tumor necrosis factor-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in tumor necrosis factor-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in tumor necrosis factor-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
Component Evidence Code Pubs
located_in cell surface IEA
Inferred from Electronic Annotation
more info
  
is_active_in external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in external side of plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in membrane raft IEA
Inferred from Electronic Annotation
more info
  
located_in membrane raft ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
Preferred Names
tumor necrosis factor receptor superfamily member 11A
Names
Paget disease of bone 2
TRANCE receptor
familial expansile osteolysis
loss of heterozygosity, 18, chromosomal region 1
osteoclast differentiation factor receptor
receptor activator of NF-KB
receptor activator of nuclear factor-kappa B
tumor necrosis factor receptor superfamily, member 11a, NFKB activator

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_008098.1 RefSeqGene

    Range
    4973..67396
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_194

mRNA and Protein(s)

  1. NM_001270949.2 → NP_001257878.1  tumor necrosis factor receptor superfamily member 11A isoform 2 precursor

    See identical proteins and their annotated locations for NP_001257878.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as delta9) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HE647782
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Conserved Domains (1) summary
    cd13411
    Location:33 → 195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

  2. NM_001270950.2 → NP_001257879.1  tumor necrosis factor receptor superfamily member 11A isoform 3 precursor

    See identical proteins and their annotated locations for NP_001257879.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as delta8,9) lacks two exons in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HE649916
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000573900.1, ENST00000903841.1
    Conserved Domains (2) summary
    cd13411
    Location:33 → 195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
    pfam05454
    Location:173 → 258
    DAG1; Dystroglycan (Dystrophin-associated glycoprotein 1)

  3. NM_001270951.2 → NP_001257880.1  tumor necrosis factor receptor superfamily member 11A isoform 4 precursor

    See identical proteins and their annotated locations for NP_001257880.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4, also known as delta7,8,9) lacks three exons in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964
    Consensus CDS
    CCDS59324.1
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000269485.7, ENST00000269485.11
    Conserved Domains (1) summary
    cd13411
    Location:33 → 195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

  4. NM_001278268.2 → NP_001265197.1  tumor necrosis factor receptor superfamily member 11A isoform 5 precursor

    See identical proteins and their annotated locations for NP_001265197.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5, also called RANK-e5a) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (5) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HF584702
    UniProtKB/TrEMBL
    A0ACI8U1W3
    Related
    ENSP00000573901.1, ENST00000903842.1
    Conserved Domains (1) summary
    cd13411
    Location:33 → 181
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

  5. NM_003839.4 → NP_003830.1  tumor necrosis factor receptor superfamily member 11A isoform 1 precursor

    See identical proteins and their annotated locations for NP_003830.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB209762, AC100843, AF018253, DA403964
    Consensus CDS
    CCDS11980.1
    UniProtKB/Swiss-Prot
    I4EC36, I4EC38, I4EC39, I7JE63, N0GVH0, Q59EP9, Q9Y6Q6
    UniProtKB/TrEMBL
    A0ACI8U1W3
    Related
    ENSP00000465500.1, ENST00000586569.3
    Conserved Domains (1) summary
    cd13411
    Location:33 → 195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    62325310..62391288
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011526245.3 → XP_011524547.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    UniProtKB/TrEMBL
    A0ACI8U086
    Conserved Domains (1) summary
    cl22855
    Location:109 → 159
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

  2. XM_011526244.3 → XP_011524546.1  tumor necrosis factor receptor superfamily member 11A isoform X1

    UniProtKB/TrEMBL
    A0ACI8RYJ9, A0ACI8U1W3
    Related
    ENSP00000573903.1, ENST00000903844.1
    Conserved Domains (1) summary
    cd13411
    Location:33 → 200
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

  3. XM_017026064.2 → XP_016881553.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    UniProtKB/TrEMBL
    A0ACI8U086
    Conserved Domains (1) summary
    cl22855
    Location:109 → 159
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

  4. XM_017026065.2 → XP_016881554.1  tumor necrosis factor receptor superfamily member 11A isoform X3

    UniProtKB/TrEMBL
    A0ACI8U1W3

  5. XM_017026066.2 → XP_016881555.1  tumor necrosis factor receptor superfamily member 11A isoform X4

    UniProtKB/TrEMBL
    A0ACI8U086

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    62528176..62594158
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054319318.1 → XP_054175293.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    UniProtKB/TrEMBL
    A0ACI8U086

  2. XM_054319316.1 → XP_054175291.1  tumor necrosis factor receptor superfamily member 11A isoform X1

    UniProtKB/TrEMBL
    A0ACI8U1W3

  3. XM_054319317.1 → XP_054175292.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    UniProtKB/TrEMBL
    A0ACI8U086

  4. XM_054319319.1 → XP_054175294.1  tumor necrosis factor receptor superfamily member 11A isoform X5

    UniProtKB/TrEMBL
    A0ACI8U086

  5. XM_054319320.1 → XP_054175295.1  tumor necrosis factor receptor superfamily member 11A isoform X3

    UniProtKB/TrEMBL
    A0ACI8U1W3

  6. XM_054319321.1 → XP_054175296.1  tumor necrosis factor receptor superfamily member 11A isoform X4

    UniProtKB/TrEMBL
    A0ACI8U086
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y6Q6.1 GenPept UniProtKB/Swiss-Prot:Q9Y6Q6

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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