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    DISP1 dispatched RND transporter family member 1 [ Homo sapiens (human) ]

    Gene ID: 84976, updated on 10-Dec-2024

    Summary

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    Official Symbol
    DISP1provided by HGNC
    Official Full Name
    dispatched RND transporter family member 1provided by HGNC
    Primary source
    HGNC:HGNC:19711
    See related
    Ensembl:ENSG00000154309 MIM:607502; AllianceGenome:HGNC:19711
    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
    DISPA
    Summary
    The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in lung (RPKM 5.0), testis (RPKM 4.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DISP1 in Genome Data Viewer
    Location:
    1q41
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (222815039..223005995)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (222048788..222239862)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (222988381..223179337)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1836 Neighboring gene uncharacterized LOC105372984 Neighboring gene family with sequence similarity 177 member B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2584 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1837 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_5246 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2585 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1838 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1839 Neighboring gene small nucleolar RNA U13 Neighboring gene NADH:ubiquinone oxidoreductase subunit B1 pseudogene 2 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:223195995-223196670 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:223197347-223198022 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:223198023-223198698 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:223198699-223199373 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:223199517-223200274 Neighboring gene 1q41-q42 HERV-mediated distal recombination region Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:223202549-223203306 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:223203307-223204064 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:223204065-223204822 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:223209992-223210672 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:223211353-223212032 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:223226073-223226573 Neighboring gene uncharacterized LOC124904520 Neighboring gene uncharacterized LOC124904521

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations. Lavillaureix A, et al. Genet Med, 2024 Jul. PMID 38529886
    2. Conserved cholesterol-related activities of Dispatched 1 drive Sonic hedgehog shedding from the cell membrane. Ehring K, et al. J Cell Sci, 2022 Mar 1. PMID 34308968, Free PMC Article
    3. Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans. Roessler E, et al. Hum Genet, 2009 May. PMID 19184110, Free PMC Article
    4. Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesis. Chen H, et al. Life Sci Alliance, 2020 Aug. PMID 32646883, Free PMC Article
    5. Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive-compulsive disorder. Lisoway AJ, et al. Hum Psychopharmacol, 2018 Jul. PMID 29953682

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.
      Title: DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.
    2. Conserved cholesterol-related activities of Dispatched 1 drive Sonic hedgehog shedding from the cell membrane.
      Title: Conserved cholesterol-related activities of Dispatched 1 drive Sonic hedgehog shedding from the cell membrane.
    3. Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.
      Title: Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.
    4. Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesis.
      Title: Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesis.
    5. Genome-wide association study does not support the role of DISP1 in predicting serotonin reuptake inhibitor response in obsessive-compulsive disorder.
      Title: Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive-compulsive disorder.
    6. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 x 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development.
      Title: Whole-genome association analysis of treatment response in obsessive-compulsive disorder.
    7. DISP-1 is required for non-small cell lung carcinoma cells proliferation
      Title: The hedgehog processing pathway is required for NSCLC growth and survival.
    8. Studies indicate that DISP1 haploinsufficiency may not be solely responsible for the major features of 1q41q42 microdeletion syndrome, and other genes in the SRO likely play a role in the phenotype.
      Title: New cases and refinement of the critical region in the 1q41q42 microdeletion syndrome.
    9. report of 1st de novo DISP1 point mutation in patient with congenital diaphragmatic hernia (CDH); finding with Disp1 embryonic mouse diaphragm and lung expression and previously reported 1q41q42 aberrations in CDH suggests DISP1 may be CDH candidate gene
      Title: Characterization of the chromosome 1q41q42.12 region, and the candidate gene DISP1, in patients with CDH.
    10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-07-06)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-07-06)

    ClinGen Genome Curation Page

    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

    • FLJ43740, MGC13130, MGC16796, MGC104180, DKFZp434I0428

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables peptide transmembrane transporter 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 determination of left/right symmetry IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in diaphragm development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in dorsal/ventral pattern formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in embryonic pattern specification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in patched ligand maturation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in peptide transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in smoothened signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    protein dispatched homolog 1
    Names
    dispatched A

    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_009243.2 RefSeqGene

      Range
      4951..195907
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001350630.2 → NP_001337559.1  protein dispatched homolog 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC093152, AL392172, BC007734, BC011542, DA062334, DA756409, HY128909
      UniProtKB/TrEMBL
      B3KPN9
      Conserved Domains (1) summary
      cl25655
      Location:192 → 850
      Patched; Patched family

    2. NM_001369594.1 → NP_001356523.1  protein dispatched homolog 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC093152
      Consensus CDS
      CCDS1536.1
      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Related
      ENSP00000284476.6, ENST00000284476.7
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    3. NM_001377228.1 → NP_001364157.1  protein dispatched homolog 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC093152, AL392172
      Consensus CDS
      CCDS1536.1
      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Related
      ENSP00000501574.1, ENST00000675039.1
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    4. NM_001377229.1 → NP_001364158.1  protein dispatched homolog 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC093152, AL392172
      Consensus CDS
      CCDS1536.1
      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Related
      ENSP00000502357.1, ENST00000675850.1
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    5. NM_032890.5 → NP_116279.2  protein dispatched homolog 1 isoform 1

      See identical proteins and their annotated locations for NP_116279.2

      Status: REVIEWED

      Source sequence(s)
      AC093152, AL392172, BC007734, BC011542, DA062334, DA756409
      Consensus CDS
      CCDS1536.1
      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    RNA

    1. NR_165109.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    2. NR_165110.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    3. NR_165111.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    4. NR_165112.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000450784.5

    5. NR_165113.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000442171.6

    6. NR_165114.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    7. NR_165115.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    8. NR_165116.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    9. NR_165117.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000435378.6

    10. NR_165118.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000426045.5

    11. NR_165119.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    12. NR_165120.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    13. NR_165121.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000657452.2

    14. NR_165122.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    15. NR_165123.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    16. NR_165124.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    17. NR_165125.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000654502.1

    18. NR_165126.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    19. NR_165127.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    20. NR_165128.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    21. NR_165129.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    22. NR_165130.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    23. NR_165131.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    24. NR_165132.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    25. NR_165133.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    26. NR_165134.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    27. NR_165135.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    28. NR_165136.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    29. NR_165137.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    30. NR_165138.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    31. NR_165139.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    32. NR_165140.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    33. NR_165141.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    34. NR_165142.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    35. NR_165143.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000434872.2

    36. NR_165144.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000457636.5

    37. NR_165145.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    38. NR_165146.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    39. NR_165147.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    40. NR_165148.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    41. NR_165149.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    42. NR_165150.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    43. NR_165151.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    44. NR_165152.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    45. NR_165153.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    46. NR_165154.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    47. NR_165155.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000661663.1

    48. NR_165156.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172

    49. NR_165157.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL392172
      Related
      ENST00000663328.2

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      222815039..223005995
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011510075.3 → XP_011508377.1  protein dispatched homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_011508377.1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    2. XM_011510073.3 → XP_011508375.1  protein dispatched homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_011508375.1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    3. XM_017002611.2 → XP_016858100.1  protein dispatched homolog 1 isoform X1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    4. XM_011510074.3 → XP_011508376.1  protein dispatched homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_011508376.1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    5. XM_011510072.3 → XP_011508374.1  protein dispatched homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_011508374.1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    6. XM_047432763.1 → XP_047288719.1  protein dispatched homolog 1 isoform X1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2

    7. XM_006711592.3 → XP_006711655.1  protein dispatched homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_006711655.1

      UniProtKB/Swiss-Prot
      Q8N7C2, Q96F81, Q96I92, Q9H698, Q9H8H9, Q9UFA2
      Conserved Domains (1) summary
      cl25655
      Location:435 → 1131
      Patched; Patched family

    8. XM_017002612.2 → XP_016858101.1  protein dispatched homolog 1 isoform X2

      UniProtKB/TrEMBL
      B3KPN9
      Conserved Domains (2) summary
      pfam02460
      Location:262 → 899
      Patched; Patched family
      cl21543
      Location:313 → 477
      MMPL; MMPL family

    9. XM_006711594.4 → XP_006711657.1  protein dispatched homolog 1 isoform X2

      See identical proteins and their annotated locations for XP_006711657.1

      UniProtKB/TrEMBL
      B3KPN9
      Conserved Domains (2) summary
      pfam02460
      Location:262 → 899
      Patched; Patched family
      cl21543
      Location:313 → 477
      MMPL; MMPL family

    10. XM_047432774.1 → XP_047288730.1  protein dispatched homolog 1 isoform X2

      UniProtKB/TrEMBL
      B3KPN9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      222048788..222239862
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339286.1 → XP_054195261.1  protein dispatched homolog 1 isoform X1

    2. XM_054339283.1 → XP_054195258.1  protein dispatched homolog 1 isoform X1

    3. XM_054339281.1 → XP_054195256.1  protein dispatched homolog 1 isoform X1

    4. XM_054339285.1 → XP_054195260.1  protein dispatched homolog 1 isoform X1

    5. XM_054339282.1 → XP_054195257.1  protein dispatched homolog 1 isoform X1

    6. XM_054339287.1 → XP_054195262.1  protein dispatched homolog 1 isoform X1

    7. XM_054339284.1 → XP_054195259.1  protein dispatched homolog 1 isoform X1

    8. XM_054339290.1 → XP_054195265.1  protein dispatched homolog 1 isoform X2

      UniProtKB/TrEMBL
      B3KPN9

    9. XM_054339288.1 → XP_054195263.1  protein dispatched homolog 1 isoform X2

      UniProtKB/TrEMBL
      B3KPN9

    10. XM_054339289.1 → XP_054195264.1  protein dispatched homolog 1 isoform X2

      UniProtKB/TrEMBL
      B3KPN9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96F81.3 GenPept UniProtKB/Swiss-Prot:Q96F81

    Gene LinkOut

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

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