Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-10

AUTHORS

David C. Whitcomb, Michael C. Gorry, Robert A. Preston, William Furey, Michael J. Sossenheimer, Charles D. Ulrich, Stephen P. Martin, Lawrence K. Gates, Stephen T. Amann, Phillip P. Toskes, Roger Liddle, Kevin McGrath, G. Uomo, J. C. Post, Garth D. Ehrlich

ABSTRACT

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg–His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis. More... »

PAGES

141-145

References to SciGraph publications

Journal

TITLE

Nature Genetics

ISSUE

2

VOLUME

14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1096-141

DOI

http://dx.doi.org/10.1038/ng1096-141

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012686614

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8841182


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Arginine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Chromosomes, Human, Pair 7", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Mutational Analysis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Enzyme Activation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Exons", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Heterozygote", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pancreatitis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pedigree", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Point Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Polymorphism, Restriction Fragment Length", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Conformation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Structure, Tertiary", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Trypsin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Trypsinogen", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.21925.3d", 
          "name": [
            "Dept of Medicine, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Depts of Medicine, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA", 
            "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Whitcomb", 
        "givenName": "David C.", 
        "id": "sg:person.01047467402.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01047467402.00"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.21925.3d", 
          "name": [
            "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gorry", 
        "givenName": "Michael C.", 
        "id": "sg:person.0763370705.14", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763370705.14"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.21925.3d", 
          "name": [
            "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Preston", 
        "givenName": "Robert A.", 
        "id": "sg:person.016613647662.83", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016613647662.83"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Crystallography, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/None", 
          "name": [
            "Crystallography, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Furey", 
        "givenName": "William", 
        "id": "sg:person.0643232527.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0643232527.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Medicine, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.21925.3d", 
          "name": [
            "Dept of Medicine, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sossenheimer", 
        "givenName": "Michael J.", 
        "id": "sg:person.012763250416.88", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012763250416.88"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA", 
          "id": "http://www.grid.ac/institutes/grid.24827.3b", 
          "name": [
            "Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ulrich", 
        "givenName": "Charles D.", 
        "id": "sg:person.0757650504.45", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0757650504.45"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA", 
          "id": "http://www.grid.ac/institutes/grid.24827.3b", 
          "name": [
            "Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Martin", 
        "givenName": "Stephen P.", 
        "id": "sg:person.014736571752.26", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014736571752.26"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Kentucky Medical Center, 40536-0084, Lexington, Kentucky, USA", 
          "id": "http://www.grid.ac/institutes/grid.461341.5", 
          "name": [
            "University of Kentucky Medical Center, 40536-0084, Lexington, Kentucky, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gates", 
        "givenName": "Lawrence K.", 
        "id": "sg:person.01177376476.74", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177376476.74"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA", 
          "id": "http://www.grid.ac/institutes/grid.15276.37", 
          "name": [
            "Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Amann", 
        "givenName": "Stephen T.", 
        "id": "sg:person.01031361067.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01031361067.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA", 
          "id": "http://www.grid.ac/institutes/grid.15276.37", 
          "name": [
            "Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Toskes", 
        "givenName": "Phillip P.", 
        "id": "sg:person.01034374142.22", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034374142.22"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA", 
          "id": "http://www.grid.ac/institutes/grid.189509.c", 
          "name": [
            "Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liddle", 
        "givenName": "Roger", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA", 
          "id": "http://www.grid.ac/institutes/grid.189509.c", 
          "name": [
            "Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "McGrath", 
        "givenName": "Kevin", 
        "id": "sg:person.01162040177.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162040177.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "XXXI Internal Medicine Unit, Ospedale Cardarelli, Naples, Italy", 
          "id": "http://www.grid.ac/institutes/grid.413172.2", 
          "name": [
            "XXXI Internal Medicine Unit, Ospedale Cardarelli, Naples, Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Uomo", 
        "givenName": "G.", 
        "id": "sg:person.01261264177.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261264177.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.239553.b", 
          "name": [
            "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Otolaryngology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Post", 
        "givenName": "J. C.", 
        "id": "sg:person.01055120221.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01055120221.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dept of Pathology, University of Pittsburgh, 737 Scaife Hall, 3350 Terrace Street, 15261, Pittsburgh, Pennsylvania, USA", 
          "id": "http://www.grid.ac/institutes/grid.21925.3d", 
          "name": [
            "Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Otolaryngology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA", 
            "Dept of Pathology, University of Pittsburgh, 737 Scaife Hall, 3350 Terrace Street, 15261, Pittsburgh, Pennsylvania, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ehrlich", 
        "givenName": "Garth D.", 
        "id": "sg:person.01324252605.57", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324252605.57"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/ng0494-384", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031523994", 
          "https://doi.org/10.1038/ng0494-384"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01318124", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045448199", 
          "https://doi.org/10.1007/bf01318124"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf02788221", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1079588052", 
          "https://doi.org/10.1007/bf02788221"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "1996-10", 
    "datePublishedReg": "1996-10-01", 
    "description": "Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg\u2013His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/ng1096-141", 
    "isAccessibleForFree": false, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2488072", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2627742", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1103138", 
        "issn": [
          "1061-4036", 
          "1546-1718"
        ], 
        "name": "Nature Genetics", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "2", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "14"
      }
    ], 
    "keywords": [
      "cationic trypsinogen gene", 
      "early-onset genetic disorders", 
      "trypsinogen gene", 
      "trypsin-sensitive sites", 
      "fail-safe mechanism", 
      "residue 117", 
      "cleavage site", 
      "unrelated individuals", 
      "genes", 
      "genetic disorders", 
      "molecular modelling", 
      "mutations", 
      "hereditary pancreatitis", 
      "digest data", 
      "structure analysis", 
      "sites", 
      "obligate carriers", 
      "phenotype", 
      "residues", 
      "Arg", 
      "trypsin", 
      "Hp phenotypes", 
      "family", 
      "autodigestion", 
      "crystal structure analysis", 
      "kindreds", 
      "individuals", 
      "mechanism", 
      "substitution", 
      "loss", 
      "analysis", 
      "X-ray crystal structure analysis", 
      "pancreas", 
      "part", 
      "disorders", 
      "data", 
      "carriers", 
      "modelling", 
      "pancreatitis", 
      "complications", 
      "serious complications", 
      "pain", 
      "epigastric pain"
    ], 
    "name": "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene", 
    "pagination": "141-145", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1012686614"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/ng1096-141"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "8841182"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/ng1096-141", 
      "https://app.dimensions.ai/details/publication/pub.1012686614"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-12-01T06:21", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_262.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/ng1096-141"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/ng1096-141'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/ng1096-141'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/ng1096-141'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/ng1096-141'


 

This table displays all metadata directly associated to this object as RDF triples.

325 TRIPLES      21 PREDICATES      91 URIs      80 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/ng1096-141 schema:about N0c218093a7034d0f9d261fbc3436b9b7
2 N0d705c8a12534a50a8e18bd8f5fcc07a
3 N1eb2b36b110c4e98a691bdf314f7b6a2
4 N207a463e26dd4e499c74d3d4c84f1c6a
5 N20932af1546e40a78e3ed9496cb01282
6 N216b60500734417698160a51fd67f2d0
7 N259adafd0ace4041aea120959b670d37
8 N2aa6546e719a422d82389325f565e09c
9 N38dbd2d745a74ba9bc1638ebe267b6d9
10 N40bd687486f1487ba25ebc272e21a3c7
11 N4e82a290c6ff4c70af62522ed38c0b87
12 N4f7e697ba4da4f628dbf9609001a6bdb
13 N650968246f4a4a57b49a9c34159f2284
14 N6cfbf06c55754373a9a79e69d9928c97
15 N8ced31cb9e18439ebc6cdea2eb4d0e6b
16 Nb59ffc4d1044453cb0fda16ade61a2d2
17 Nda74a570e20a4425b079381f499d7f87
18 Ne03923ad25104588ac021d23cbd6b25c
19 Nf36d7de8202447eb87a9cfbaba4f41cb
20 anzsrc-for:06
21 anzsrc-for:0604
22 schema:author Nc312146501af47a5a2c5c313465ae51f
23 schema:citation sg:pub.10.1007/bf01318124
24 sg:pub.10.1007/bf02788221
25 sg:pub.10.1038/ng0494-384
26 schema:datePublished 1996-10
27 schema:datePublishedReg 1996-10-01
28 schema:description Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg–His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.
29 schema:genre article
30 schema:isAccessibleForFree false
31 schema:isPartOf N2140acdd0e9d47c392e4414ac3787964
32 N885c74998dec435c95309a0440c0bd92
33 sg:journal.1103138
34 schema:keywords Arg
35 Hp phenotypes
36 X-ray crystal structure analysis
37 analysis
38 autodigestion
39 carriers
40 cationic trypsinogen gene
41 cleavage site
42 complications
43 crystal structure analysis
44 data
45 digest data
46 disorders
47 early-onset genetic disorders
48 epigastric pain
49 fail-safe mechanism
50 family
51 genes
52 genetic disorders
53 hereditary pancreatitis
54 individuals
55 kindreds
56 loss
57 mechanism
58 modelling
59 molecular modelling
60 mutations
61 obligate carriers
62 pain
63 pancreas
64 pancreatitis
65 part
66 phenotype
67 residue 117
68 residues
69 serious complications
70 sites
71 structure analysis
72 substitution
73 trypsin
74 trypsin-sensitive sites
75 trypsinogen gene
76 unrelated individuals
77 schema:name Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene
78 schema:pagination 141-145
79 schema:productId N69a61973d9184eb4961d0348561c81e2
80 N74c52f8598d6476f94bb7c565f176890
81 Nd7dc2049f3904849a96207e9d29311f6
82 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012686614
83 https://doi.org/10.1038/ng1096-141
84 schema:sdDatePublished 2022-12-01T06:21
85 schema:sdLicense https://scigraph.springernature.com/explorer/license/
86 schema:sdPublisher Nf7dd302b83fe477f834e97fa7d38798d
87 schema:url https://doi.org/10.1038/ng1096-141
88 sgo:license sg:explorer/license/
89 sgo:sdDataset articles
90 rdf:type schema:ScholarlyArticle
91 N0c218093a7034d0f9d261fbc3436b9b7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
92 schema:name Humans
93 rdf:type schema:DefinedTerm
94 N0d705c8a12534a50a8e18bd8f5fcc07a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
95 schema:name Genes
96 rdf:type schema:DefinedTerm
97 N1cc5df3bfbcd4166b1628b2f71eb21be rdf:first sg:person.012763250416.88
98 rdf:rest N8a22d34b7b664bb1ad1d6e8b77eb3abd
99 N1eb2b36b110c4e98a691bdf314f7b6a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name Trypsin
101 rdf:type schema:DefinedTerm
102 N207a463e26dd4e499c74d3d4c84f1c6a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
103 schema:name Heterozygote
104 rdf:type schema:DefinedTerm
105 N20932af1546e40a78e3ed9496cb01282 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name DNA Mutational Analysis
107 rdf:type schema:DefinedTerm
108 N2140acdd0e9d47c392e4414ac3787964 schema:issueNumber 2
109 rdf:type schema:PublicationIssue
110 N216b60500734417698160a51fd67f2d0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Pancreatitis
112 rdf:type schema:DefinedTerm
113 N2509034626ee4045923ee3d576dab2c9 rdf:first sg:person.0763370705.14
114 rdf:rest Nd6c4b405d9e940b0a423bde0f3657592
115 N259adafd0ace4041aea120959b670d37 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
116 schema:name Point Mutation
117 rdf:type schema:DefinedTerm
118 N2aa6546e719a422d82389325f565e09c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Enzyme Activation
120 rdf:type schema:DefinedTerm
121 N35aaa4eb73cf4593894dd8ddc59af479 schema:affiliation grid-institutes:grid.189509.c
122 schema:familyName Liddle
123 schema:givenName Roger
124 rdf:type schema:Person
125 N38dbd2d745a74ba9bc1638ebe267b6d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
126 schema:name Polymorphism, Restriction Fragment Length
127 rdf:type schema:DefinedTerm
128 N40bd687486f1487ba25ebc272e21a3c7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
129 schema:name Exons
130 rdf:type schema:DefinedTerm
131 N47016e2666904e74a6fc98c4c866d9aa rdf:first sg:person.01177376476.74
132 rdf:rest N52295aa1dc474401a1bb509594ee07ed
133 N477a56b5be134f72a919818f12c5523f rdf:first N35aaa4eb73cf4593894dd8ddc59af479
134 rdf:rest N7d00fea597ac45938df07c30194a95ab
135 N4e82a290c6ff4c70af62522ed38c0b87 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
136 schema:name Female
137 rdf:type schema:DefinedTerm
138 N4f7e697ba4da4f628dbf9609001a6bdb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
139 schema:name Models, Molecular
140 rdf:type schema:DefinedTerm
141 N52295aa1dc474401a1bb509594ee07ed rdf:first sg:person.01031361067.35
142 rdf:rest Na9159b1259d244f6aaceaef576f5caa9
143 N650968246f4a4a57b49a9c34159f2284 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Trypsinogen
145 rdf:type schema:DefinedTerm
146 N69a61973d9184eb4961d0348561c81e2 schema:name doi
147 schema:value 10.1038/ng1096-141
148 rdf:type schema:PropertyValue
149 N6cfbf06c55754373a9a79e69d9928c97 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Arginine
151 rdf:type schema:DefinedTerm
152 N74c52f8598d6476f94bb7c565f176890 schema:name dimensions_id
153 schema:value pub.1012686614
154 rdf:type schema:PropertyValue
155 N7d00fea597ac45938df07c30194a95ab rdf:first sg:person.01162040177.41
156 rdf:rest Nf5b764f77d4d4b118eb33487891affda
157 N831eb222aba64bd394c1c45d7e11cad5 rdf:first sg:person.01324252605.57
158 rdf:rest rdf:nil
159 N8514a46575a3405ebc73891737138cb3 rdf:first sg:person.014736571752.26
160 rdf:rest N47016e2666904e74a6fc98c4c866d9aa
161 N885c74998dec435c95309a0440c0bd92 schema:volumeNumber 14
162 rdf:type schema:PublicationVolume
163 N8a22d34b7b664bb1ad1d6e8b77eb3abd rdf:first sg:person.0757650504.45
164 rdf:rest N8514a46575a3405ebc73891737138cb3
165 N8ced31cb9e18439ebc6cdea2eb4d0e6b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name Male
167 rdf:type schema:DefinedTerm
168 Na9159b1259d244f6aaceaef576f5caa9 rdf:first sg:person.01034374142.22
169 rdf:rest N477a56b5be134f72a919818f12c5523f
170 Nb59ffc4d1044453cb0fda16ade61a2d2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Protein Conformation
172 rdf:type schema:DefinedTerm
173 Nc312146501af47a5a2c5c313465ae51f rdf:first sg:person.01047467402.00
174 rdf:rest N2509034626ee4045923ee3d576dab2c9
175 Ncbb889efc66344499de52143eb4d17a9 rdf:first sg:person.01055120221.02
176 rdf:rest N831eb222aba64bd394c1c45d7e11cad5
177 Nd6c4b405d9e940b0a423bde0f3657592 rdf:first sg:person.016613647662.83
178 rdf:rest Nf06b7c0cfdbc41eaa6c4e1f31c63885c
179 Nd7dc2049f3904849a96207e9d29311f6 schema:name pubmed_id
180 schema:value 8841182
181 rdf:type schema:PropertyValue
182 Nda74a570e20a4425b079381f499d7f87 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Protein Structure, Tertiary
184 rdf:type schema:DefinedTerm
185 Ne03923ad25104588ac021d23cbd6b25c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name Chromosomes, Human, Pair 7
187 rdf:type schema:DefinedTerm
188 Nf06b7c0cfdbc41eaa6c4e1f31c63885c rdf:first sg:person.0643232527.52
189 rdf:rest N1cc5df3bfbcd4166b1628b2f71eb21be
190 Nf36d7de8202447eb87a9cfbaba4f41cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
191 schema:name Pedigree
192 rdf:type schema:DefinedTerm
193 Nf5b764f77d4d4b118eb33487891affda rdf:first sg:person.01261264177.41
194 rdf:rest Ncbb889efc66344499de52143eb4d17a9
195 Nf7dd302b83fe477f834e97fa7d38798d schema:name Springer Nature - SN SciGraph project
196 rdf:type schema:Organization
197 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
198 schema:name Biological Sciences
199 rdf:type schema:DefinedTerm
200 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
201 schema:name Genetics
202 rdf:type schema:DefinedTerm
203 sg:grant.2488072 http://pending.schema.org/fundedItem sg:pub.10.1038/ng1096-141
204 rdf:type schema:MonetaryGrant
205 sg:grant.2627742 http://pending.schema.org/fundedItem sg:pub.10.1038/ng1096-141
206 rdf:type schema:MonetaryGrant
207 sg:journal.1103138 schema:issn 1061-4036
208 1546-1718
209 schema:name Nature Genetics
210 schema:publisher Springer Nature
211 rdf:type schema:Periodical
212 sg:person.01031361067.35 schema:affiliation grid-institutes:grid.15276.37
213 schema:familyName Amann
214 schema:givenName Stephen T.
215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01031361067.35
216 rdf:type schema:Person
217 sg:person.01034374142.22 schema:affiliation grid-institutes:grid.15276.37
218 schema:familyName Toskes
219 schema:givenName Phillip P.
220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034374142.22
221 rdf:type schema:Person
222 sg:person.01047467402.00 schema:affiliation grid-institutes:grid.21925.3d
223 schema:familyName Whitcomb
224 schema:givenName David C.
225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01047467402.00
226 rdf:type schema:Person
227 sg:person.01055120221.02 schema:affiliation grid-institutes:grid.239553.b
228 schema:familyName Post
229 schema:givenName J. C.
230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01055120221.02
231 rdf:type schema:Person
232 sg:person.01162040177.41 schema:affiliation grid-institutes:grid.189509.c
233 schema:familyName McGrath
234 schema:givenName Kevin
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162040177.41
236 rdf:type schema:Person
237 sg:person.01177376476.74 schema:affiliation grid-institutes:grid.461341.5
238 schema:familyName Gates
239 schema:givenName Lawrence K.
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177376476.74
241 rdf:type schema:Person
242 sg:person.01261264177.41 schema:affiliation grid-institutes:grid.413172.2
243 schema:familyName Uomo
244 schema:givenName G.
245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261264177.41
246 rdf:type schema:Person
247 sg:person.012763250416.88 schema:affiliation grid-institutes:grid.21925.3d
248 schema:familyName Sossenheimer
249 schema:givenName Michael J.
250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012763250416.88
251 rdf:type schema:Person
252 sg:person.01324252605.57 schema:affiliation grid-institutes:grid.21925.3d
253 schema:familyName Ehrlich
254 schema:givenName Garth D.
255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324252605.57
256 rdf:type schema:Person
257 sg:person.014736571752.26 schema:affiliation grid-institutes:grid.24827.3b
258 schema:familyName Martin
259 schema:givenName Stephen P.
260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014736571752.26
261 rdf:type schema:Person
262 sg:person.016613647662.83 schema:affiliation grid-institutes:grid.21925.3d
263 schema:familyName Preston
264 schema:givenName Robert A.
265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016613647662.83
266 rdf:type schema:Person
267 sg:person.0643232527.52 schema:affiliation grid-institutes:None
268 schema:familyName Furey
269 schema:givenName William
270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0643232527.52
271 rdf:type schema:Person
272 sg:person.0757650504.45 schema:affiliation grid-institutes:grid.24827.3b
273 schema:familyName Ulrich
274 schema:givenName Charles D.
275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0757650504.45
276 rdf:type schema:Person
277 sg:person.0763370705.14 schema:affiliation grid-institutes:grid.21925.3d
278 schema:familyName Gorry
279 schema:givenName Michael C.
280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763370705.14
281 rdf:type schema:Person
282 sg:pub.10.1007/bf01318124 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045448199
283 https://doi.org/10.1007/bf01318124
284 rdf:type schema:CreativeWork
285 sg:pub.10.1007/bf02788221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1079588052
286 https://doi.org/10.1007/bf02788221
287 rdf:type schema:CreativeWork
288 sg:pub.10.1038/ng0494-384 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031523994
289 https://doi.org/10.1038/ng0494-384
290 rdf:type schema:CreativeWork
291 grid-institutes:None schema:alternateName Crystallography, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA
292 schema:name Crystallography, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA
293 rdf:type schema:Organization
294 grid-institutes:grid.15276.37 schema:alternateName Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA
295 schema:name Depts of Gastroenterology, Hepatology and Nutrition at the University of Florida School of Medicine, 32610-0214, Gainsville, Florida, USA
296 rdf:type schema:Organization
297 grid-institutes:grid.189509.c schema:alternateName Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA
298 schema:name Dept of Medicine at Duke University Medical Center, 27710, Durham, North Carolina, USA
299 rdf:type schema:Organization
300 grid-institutes:grid.21925.3d schema:alternateName Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
301 Dept of Medicine, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
302 Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
303 Dept of Pathology, University of Pittsburgh, 737 Scaife Hall, 3350 Terrace Street, 15261, Pittsburgh, Pennsylvania, USA
304 schema:name Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
305 Dept of Medicine, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
306 Dept of Otolaryngology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
307 Dept of Pathology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
308 Dept of Pathology, University of Pittsburgh, 737 Scaife Hall, 3350 Terrace Street, 15261, Pittsburgh, Pennsylvania, USA
309 Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA
310 Depts of Medicine, Pittsburgh Veterans Affairs Medical Center (VAMC), 15240, Pittsburgh, Pennsylvania, USA
311 rdf:type schema:Organization
312 grid-institutes:grid.239553.b schema:alternateName Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA
313 schema:name Center for Genomic Sciences, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
314 Dept of Otolaryngology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, Pennsylvania, USA
315 Dept of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (CUP), 15213, Pittsburgh, Pennsylvania, USA
316 rdf:type schema:Organization
317 grid-institutes:grid.24827.3b schema:alternateName Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA
318 schema:name Division of Digestive Diseases at the University of Cincinnati, 45267-0595, Cincinnati, Ohio, USA
319 rdf:type schema:Organization
320 grid-institutes:grid.413172.2 schema:alternateName XXXI Internal Medicine Unit, Ospedale Cardarelli, Naples, Italy
321 schema:name XXXI Internal Medicine Unit, Ospedale Cardarelli, Naples, Italy
322 rdf:type schema:Organization
323 grid-institutes:grid.461341.5 schema:alternateName University of Kentucky Medical Center, 40536-0084, Lexington, Kentucky, USA
324 schema:name University of Kentucky Medical Center, 40536-0084, Lexington, Kentucky, USA
325 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...