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PTCH1 patched homolog 1 (Drosophila)

Identity

Other namesPTC, but this term was confusing with PTC/PKA
PTCH
patched
HGNC (Hugo) PTCH1
LocusID (NCBI) 5727
Location 9q22.32
Location_base_pair Starts at 98205264 and ends at 98270831 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order (between FACC and XPAC PTCH1 is flanked by the microsatellite markers D9S196 and D9S287; a microsatellite marker, 1AJL, is located inside the gene

DNA/RNA

Description 24 exons, exon 24 is non-coding; 34 kb
Transcription alternate splicing: 3 different 5' termini; 6.5 kb mRNA; coding sequence: CDS 1 ... 4344

Protein

Description glycoprotein; 12 transmembrane domains, 2 extra cellular loops, intracellular N-term and C-term and sterol-sensing domain (SSD)
Expression widely expressed at low levels; increased levels in cells receiving a hedgehog signal
Localisation transmembrane protein, cellular membrane, intracellular vesicles
Function part of a signalling pathway; opposed by the gene products of hedgehog genes; transmembrane protein; is thought to have a repressive activity on cell proliferation; the recent demonstration of NBCCS syndrome (see below) as a chromosome instability syndrome suggests that this protein has a role in DNA maintenance, repair and/or replication
Homology patched (drosophila segment polarity gene), PTCH2 (human gene with unknown function)

Mutations

Germinal germ-line mutations lead to protein truncation in naevoid basal cell carcinoma syndrome (NBCCS) patients (see below); mutations types are variable : nucleotide substitutions (missense/nonsense), small deletions, or small insertions mainly, leading to protein truncation; these mutations have been observed in most exons; there is, so far, no hot-spot.
Somatic mutation and allele loss events in basal cell carcinoma, in NBCCS and in sporadic basal cell carcinoma are, so far, in accordance with the two-hit model for neoplasia, as is found in retinoblastoma; mutation and allele loss have also been found in sporadic primitive neuroectodermal tumours (PNETs), sporadic medulloblastomas and in a few cases of esophageal squamous cell carcinoma and invasive transitional cell carcinoma of the bladder; mutations have also been reported in a low frequency of sporadic trichoepitheliomas and in sporadic odontogenic keratocysts

Implicated in

Entity naevoid basal cell carcinoma syndrome (NBCCS) or Gorlin syndrome
Disease autosomal dominant condition; cancer prone disease (multiple basal cell carcinomas, medulloblastomas); malformations; it is also a chromosome instability syndrome
Cytogenetics spontaneous and induced chromosome instability
  
Entity skin cancers
Disease
  • sporadic basal cell carcinoma, but also in the benign trichoepithelioma, a tumor often associated with basal cell carcinomas
  • sporadic basal cell carcinoma from xeroderma pigmentosum patients have a high frequency of typical UV-induced mutations in PTCH1
  •   
    Entity brain diseases
    Disease
  • in a subset of sporadic primitive neuroectodermal tumours (PNETs)of the central nervous system (cerebral PNETs, medulloblastomas, and desmoplastic medulloblastomas); note: NBCCS patients have a predisposition for the development of PNETs, while, herein mentioned are sporadic PNETs
  • PTCH1 have also been found mutated in both familiar and sporadic cases of Holoprosencephaly (HPE)
  •   
    Entity various cancers and benign tumors
    Disease
  • invasive transitional cell carcinoma of the bladder: PTCH1 has been found mutated in rare cases
  • sporadic esophageal squamous cell carcinoma
  • jaws: in sporadic odontogenic keratocysts and in odontogenic keratocysts from NBCCS patients
  •   

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

    External links

    Nomenclature
    HGNC (Hugo)PTCH1   9585
    Cards
    AtlasPTCHID100
    Entrez_Gene (NCBI)PTCH1  5727  patched 1
    GeneCards (Weizmann)PTCH1
    Ensembl (Hinxton)ENSG00000185920 [Gene_View]  chr9:98205264-98270831 [Contig_View]  PTCH1 [Vega]
    ICGC DataPortalENSG00000185920
    cBioPortalPTCH1
    AceView (NCBI)PTCH1
    Genatlas (Paris)PTCH1
    WikiGenes5727
    SOURCE (Princeton)NM_000264 NM_001083602 NM_001083603 NM_001083604 NM_001083605 NM_001083606 NM_001083607
    Genomic and cartography
    GoldenPath (UCSC)PTCH1  -  9q22.32   chr9:98205264-98270831 -  9q22.1-q31   [Description]    (hg19-Feb_2009)
    EnsemblPTCH1 - 9q22.1-q31 [CytoView]
    Mapping of homologs : NCBIPTCH1 [Mapview]
    OMIM109400   601309   605462   610828   
    Gene and transcription
    Genbank (Entrez)AB189436 AB189437 AB189438 AB189439 AB189440
    RefSeq transcript (Entrez)NM_000264 NM_001083602 NM_001083603 NM_001083604 NM_001083605 NM_001083606 NM_001083607
    RefSeq genomic (Entrez)AC_000141 NC_000009 NC_018920 NG_007664 NT_008470 NW_001839235 NW_004929366
    Consensus coding sequences : CCDS (NCBI)PTCH1
    Cluster EST : UnigeneHs.494538 [ NCBI ]
    CGAP (NCI)Hs.494538
    Alternative Splicing : Fast-db (Paris)GSHG0030981
    Alternative Splicing GalleryENSG00000185920
    Gene ExpressionPTCH1 [ NCBI-GEO ]     PTCH1 [ SEEK ]   PTCH1 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ13635 (Uniprot)
    NextProtQ13635  [Medical]
    With graphics : InterProQ13635
    Splice isoforms : SwissVarQ13635 (Swissvar)
    Domaine pattern : Prosite (Expaxy)SSD (PS50156)   
    Domains : Interpro (EBI)Patched [organisation]   SSD [organisation]   TM_rcpt_patched [organisation]  
    Related proteins : CluSTrQ13635
    Domain families : Pfam (Sanger)Patched (PF02460)   
    Domain families : Pfam (NCBI)pfam02460   
    DMDM Disease mutations5727
    Blocks (Seattle)Q13635
    Human Protein AtlasENSG00000185920 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasQ13635
    HPRD03200
    IPIIPI00014374   IPI00654901   IPI00844057   IPI00643862   IPI01013890   IPI00654873   IPI01010130   IPI00446209   IPI00654566   IPI01022812   IPI01022034   IPI01022701   IPI01021039   IPI01020762   IPI01022415   IPI00478703   
    Protein Interaction databases
    DIP (DOE-UCLA)Q13635
    IntAct (EBI)Q13635
    FunCoupENSG00000185920
    BioGRIDPTCH1
    InParanoidQ13635
    Interologous Interaction database Q13635
    IntegromeDBPTCH1
    STRING (EMBL)PTCH1
    Ontologies - Pathways
    Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  branching involved in ureteric bud morphogenesis  neural tube closure  heart morphogenesis  patched binding  smoothened binding  protein binding  Golgi apparatus  plasma membrane  caveola  smoothened signaling pathway  smoothened signaling pathway  regulation of mitotic cell cycle  brain development  hedgehog receptor activity  heparin binding  epidermis development  regulation of smoothened signaling pathway  response to mechanical stimulus  organ morphogenesis  dorsal/ventral pattern formation  response to chlorate  positive regulation of cholesterol efflux  postsynaptic density  cholesterol binding  integral component of membrane  protein processing  spinal cord motor neuron differentiation  neural tube patterning  neural plate axis specification  embryonic limb morphogenesis  cyclin binding  midbody  response to estradiol  protein complex binding  response to retinoic acid  regulation of protein localization  limb morphogenesis  hindlimb morphogenesis  negative regulation of multicellular organism growth  response to drug  glucose homeostasis  intracellular membrane-bounded organelle  negative regulation of sequence-specific DNA binding transcription factor activity  keratinocyte proliferation  dendritic growth cone  axonal growth cone  negative regulation of osteoblast differentiation  negative regulation of smoothened signaling pathway  negative regulation of smoothened signaling pathway  perinuclear region of cytoplasm  negative regulation of epithelial cell proliferation  negative regulation of cell division  pharyngeal system development  mammary gland duct morphogenesis  mammary gland epithelial cell differentiation  smoothened signaling pathway involved in dorsal/ventral neural tube patterning  cell differentiation involved in kidney development  somite development  cellular response to cholesterol  cellular response to cholesterol  renal system development  cell proliferation involved in metanephros development  primary cilium  protein targeting to plasma membrane  hedgehog family protein binding  
    Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  branching involved in ureteric bud morphogenesis  neural tube closure  heart morphogenesis  patched binding  smoothened binding  protein binding  Golgi apparatus  plasma membrane  caveola  smoothened signaling pathway  smoothened signaling pathway  regulation of mitotic cell cycle  brain development  hedgehog receptor activity  heparin binding  epidermis development  regulation of smoothened signaling pathway  response to mechanical stimulus  organ morphogenesis  dorsal/ventral pattern formation  response to chlorate  positive regulation of cholesterol efflux  postsynaptic density  cholesterol binding  integral component of membrane  protein processing  spinal cord motor neuron differentiation  neural tube patterning  neural plate axis specification  embryonic limb morphogenesis  cyclin binding  midbody  response to estradiol  protein complex binding  response to retinoic acid  regulation of protein localization  limb morphogenesis  hindlimb morphogenesis  negative regulation of multicellular organism growth  response to drug  glucose homeostasis  intracellular membrane-bounded organelle  negative regulation of sequence-specific DNA binding transcription factor activity  keratinocyte proliferation  dendritic growth cone  axonal growth cone  negative regulation of osteoblast differentiation  negative regulation of smoothened signaling pathway  negative regulation of smoothened signaling pathway  perinuclear region of cytoplasm  negative regulation of epithelial cell proliferation  negative regulation of cell division  pharyngeal system development  mammary gland duct morphogenesis  mammary gland epithelial cell differentiation  smoothened signaling pathway involved in dorsal/ventral neural tube patterning  cell differentiation involved in kidney development  somite development  cellular response to cholesterol  cellular response to cholesterol  renal system development  cell proliferation involved in metanephros development  primary cilium  protein targeting to plasma membrane  hedgehog family protein binding  
    Pathways : BIOCARTASonic Hedgehog (Shh) Pathway [Genes]    Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle [Genes]   
    Pathways : KEGGHedgehog signaling pathway    Pathways in cancer    Proteoglycans in cancer    Basal cell carcinoma   
    Protein Interaction DatabasePTCH1
    Wikipedia pathwaysPTCH1
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)PTCH1
    snp3D : Map Gene to Disease5727
    SNP (GeneSNP Utah)PTCH1
    SNP : HGBasePTCH1
    Genetic variants : HAPMAPPTCH1
    Exome VariantPTCH1
    1000_GenomesPTCH1 
    ICGC programENSG00000185920 
    Cancer Gene: CensusPTCH1 
    Somatic Mutations in Cancer : COSMICPTCH1 
    CONAN: Copy Number AnalysisPTCH1 
    Mutations and Diseases : HGMDPTCH1
    Mutations and Diseases : intOGenPTCH1
    Genomic VariantsPTCH1  PTCH1 [DGVbeta]
    dbVarPTCH1
    ClinVarPTCH1
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM109400    601309    605462    610828   
    MedgenPTCH1
    GENETestsPTCH1
    Disease Genetic AssociationPTCH1
    Huge Navigator PTCH1 [HugePedia]  PTCH1 [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGenePTCH1
    Homology/Alignments : Family Browser (UCSC)PTCH1
    Phylogenetic Trees/Animal Genes : TreeFamPTCH1
    Chemical/Protein Interactions : CTD5727
    Chemical/Pharm GKB GenePA33937
    Clinical trialPTCH1
    Cancer Resource (Charite)ENSG00000185920
    Other databases
    Other databaseLocus specific database; PTCH Mutation Database
    Probes
    Litterature
    PubMed188 Pubmed reference(s) in Entrez
    CoreMinePTCH1
    iHOPPTCH1
    OncoSearchPTCH1

    Bibliography

    The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation.
    Tabata T, Eaton S, Kornberg TB
    Genes & development. 1992 ; 6 (12B) : 2635-2645.
    PMID 1340474
     
    Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
    Basler K, Struhl G
    Nature. 1994 ; 368 (6468) : 208-214.
    PMID 8145818
     
    The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.
    Capdevila J, Estrada MP, Snchez-Herrero E, Guerrero I
    The EMBO journal. 1994 ; 13 (1) : 71-82.
    PMID 8306973
     
    The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.
    Gailani MR, Sthle-Bckdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Undn AB, Dean M, Brash DE, Bale AE, Toftgrd R
    Nature genetics. 1996 ; 14 (1) : 78-81.
    PMID 8782823
     
    A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities.
    Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M, Wainwright B
    The Journal of biological chemistry. 1996 ; 271 (21) : 12125-12128.
    PMID 8647801
     
    Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.
    Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE
    Cell. 1996 ; 85 (6) : 841-851.
    PMID 8681379
     
    Human homolog of patched, a candidate gene for the basal cell nevus syndrome.
    Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP
    Science (New York, N.Y.). 1996 ; 272 (5268) : 1668-1671.
    PMID 8658145
     
    Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome.
    Lench NJ, Telford EA, High AS, Markham AF, Wicking C, Wainwright BJ
    Human genetics. 1997 ; 100 (5-6) : 497-502.
    PMID 9341860
     
    Sporadic medulloblastomas contain PTCH mutations.
    Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD
    Cancer research. 1997 ; 57 (5) : 842-845.
    PMID 9041183
     
    Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis.
    Vorechovsk I, Undn AB, Sandstedt B, Toftgrd R, Sthle-Bckdahl M
    Cancer research. 1997 ; 57 (21) : 4677-4681.
    PMID 9354420
     
    Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident.
    Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G
    American journal of human genetics. 1997 ; 60 (1) : 21-26.
    PMID 8981943
     
    Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.
    Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G
    Cancer research. 1997 ; 57 (13) : 2581-2585.
    PMID 9205058
     
    Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.
    Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein EH Jr
    Cancer research. 1997 ; 57 (12) : 2369-2372.
    PMID 9192811
     
    Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome.
    Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, Zhang X, Scott MP, Epstein EH Jr
    The Journal of investigative dermatology. 1998 ; 110 (6) : 885-888.
    PMID 9620294
     
    Patching together the genetics of Gorlin syndrome.
    Bale SJ, Falk RT, Rogers GR
    Journal of cutaneous medicine and surgery. 1998 ; 3 (1) : 31-34.
    PMID 9677257
     
    Dinucleotide repeat polymorphism within the tumor suppressor gene PTCH at 9q22.
    Louhelainen J, Lindstrm E, Hemminki K, Toftgrd R
    Clinical genetics. 1998 ; 54 (3) : 239-241.
    PMID 9788729
     
    Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma.
    Maesawa C, Tamura G, Iwaya T, Ogasawara S, Ishida K, Sato N, Nishizuka S, Suzuki Y, Ikeda K, Aoki K, Saito K, Satodate R
    Genes, chromosomes & cancer. 1998 ; 21 (3) : 276-279.
    PMID 9523206
     
    PTCH gene mutations in invasive transitional cell carcinoma of the bladder.
    McGarvey TW, Maruta Y, Tomaszewski JE, Linnenbach AJ, Malkowicz SB
    Oncogene. 1998 ; 17 (9) : 1167-1172.
    PMID 9764827
     
    Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly.
    Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M
    Human genetics. 2002 ; 110 (4) : 297-301.
    PMID 11941477
     
    The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal instability syndrome.
    Shafei-Benaissa E, Savage JR, Babin P, Larrgue M, Papworth D, Tanzer J, Bonnetblanc JM, Huret JL
    Mutation research. 1998 ; 397 (2) : 287-292.
    PMID 9541654
     
    High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum.
    Bodak N, Queille S, Avril MF, Bouadjar B, Drougard C, Sarasin A, Daya-Grosjean L
    Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (9) : 5117-5122.
    PMID 10220428
     
    The hedgehog signalling pathway and its role in basal cell carcinoma.
    Booth DR
    Cancer metastasis reviews. 1999 ; 18 (2) : 261-284.
    PMID 10728988
     
    PTCH gene mutations in odontogenic keratocysts.
    Barreto DC, Gomez RS, Bale AE, Boson WL, De Marco L
    Journal of dental research. 2000 ; 79 (6) : 1418-1422.
    PMID 10890722
     
    UV-specific mutations of the human patched gene in basal cell carcinomas from normal individuals and xeroderma pigmentosum patients.
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    PMID 10838143
     
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    PMID 10656695
     
    Identification of PATCHED mutations in medulloblastomas by direct sequencing.
    Dong J, Gailani MR, Pomeroy SL, Reardon D, Bale AE
    Human mutation. 2000 ; 16 (1) : 89-90.
    PMID 10874314
     
    The spectrum of patched mutations in a collection of Australian basal cell carcinomas.
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    Hum Mut. 2000 ; 16 (numero 1) : 43-48.
    PMID 20334495
     
    Hedgehog signaling in animal development and human disease.
    Bailey EC, Scott MP, Johnson RL
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    Hedgehog signalling in cancer.
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    PMID 11130178
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written05-1997Jean-Loup Huret
    -
    Updated01-1999Jean-Loup Huret
    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
    Updated12-2000Erika Lindström, Rune Toftgård
    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

    Citation

    This paper should be referenced as such :
    Lindstr
    PTCH1 (patched homolog 1 (Drosophila))
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):16-18.
    Free online version   Free pdf version   [Bibliographic record ]
    History of this paper:
    Lindstr. PTCH1 (patched homolog 1 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):16-18.
    http://documents.irevues.inist.fr/bitstream/2042/37694/1/12-2000-PTCH100.pdf
    Atlas Genet Cytogenet Oncol Haematol. January 1999
    http://documents.irevues.inist.fr/bitstream/handle/2042/32018/05-1997-PTCH100.pdf
    URL : http://AtlasGeneticsOncology.org/Genes/PTCHID100.html

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    indexed on : Sat Oct 4 13:09:30 CEST 2014

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