PTCH1 patched homolog 1 (Drosophila)

2000-12-01   Erika Lindström , Rune Toftgœrd 

Identity

HGNC
LOCATION
9q22.32
LOCUSID
ALIAS
BCNS,NBCCS,PTC,PTC1,PTCH
FUSION GENES

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

Proteins

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 name
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 name
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 name
    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 name
    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
  • Bibliography

    Pubmed IDLast YearTitleAuthors
    96202941998Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome.Aszterbaum M et al
    109433122000Hedgehog signaling in animal development and human disease.Bailey EC et al
    96772571998Patching together the genetics of Gorlin syndrome.Bale SJ et al
    108907222000PTCH gene mutations in odontogenic keratocysts.Barreto DC et al
    81458181994Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.Basler K et al
    102204281999High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum.Bodak N et al
    107289881999The hedgehog signalling pathway and its role in basal cell carcinoma.Booth DR et al
    83069731994The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.Capdevila J et al
    106566952000UV mutation signature in tumor suppressor genes involved in skin carcinogenesis in xeroderma pigmentosum patients.D'Errico M et al
    108381432000UV-specific mutations of the human patched gene in basal cell carcinomas from normal individuals and xeroderma pigmentosum patients.Daya-Grosjean L et al
    108743142000Identification of PATCHED mutations in medulloblastomas by direct sequencing.Dong J et al
    203344952010Structure, organization and nucleotide diversity of the mitochondrial control region and cytochrome b of southern water vole (Arvicola sapidus).Centeno-Cuadros A et al
    87828231996The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.Gailani MR et al
    86478011996A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities.Hahn H et al
    86813791996Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.Hahn H et al
    86581451996Human homolog of patched, a candidate gene for the basal cell nevus syndrome.Johnson RL et al
    93418601997Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome.Lench NJ et al
    97887291998Dinucleotide repeat polymorphism within the tumor suppressor gene PTCH at 9q22.Louhelainen J et al
    95232061998Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma.Maesawa C et al
    97648271998PTCH gene mutations in invasive transitional cell carcinoma of the bladder.McGarvey TW et al
    119414772002Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly.Ming JE et al
    90411831997Sporadic medulloblastomas contain PTCH mutations.Raffel C et al
    95416541998The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal instability syndrome.Shafei-Benaissa E et al
    13404741992The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation.Tabata T et al
    111301782000Hedgehog signalling in cancer.Toftgård R et al
    93544201997Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis.Vorechovský I et al
    89819431997Most 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 et al
    92050581997Mutations 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 et al
    91928111997Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.Xie J et al

    Other Information

    Locus ID:

    NCBI: 5727
    MIM: 601309
    HGNC: 9585
    Ensembl: ENSG00000185920

    Variants:

    dbSNP: 5727
    ClinVar: 5727
    TCGA: ENSG00000185920
    COSMIC: PTCH1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000185920ENST00000331920Q13635
    ENSG00000185920ENST00000375271H0Y3B8
    ENSG00000185920ENST00000375274Q13635
    ENSG00000185920ENST00000375290H3BLX7
    ENSG00000185920ENST00000418258Q13635
    ENSG00000185920ENST00000421141Q13635
    ENSG00000185920ENST00000429896Q13635
    ENSG00000185920ENST00000430669Q13635
    ENSG00000185920ENST00000437951Q13635
    ENSG00000185920ENST00000468211A0A0C4DGJ5
    ENSG00000185920ENST00000546820A0A0C4DGI4
    ENSG00000185920ENST00000547672A0A0C4DGI4
    ENSG00000185920ENST00000548420F8VXL8
    ENSG00000185920ENST00000550914F8VPA3
    ENSG00000185920ENST00000551623H0YHK0
    ENSG00000185920ENST00000551630F8VQS6
    ENSG00000185920ENST00000551845A0A0C4DGI4
    ENSG00000185920ENST00000553011A0A0C4DGI4

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    35
    40

    Pathways

    PathwaySourceExternal ID
    Hedgehog signaling pathwayKEGGko04340
    Axon guidanceKEGGko04360
    Basal cell carcinomaKEGGko05217
    Hedgehog signaling pathwayKEGGhsa04340
    Axon guidanceKEGGhsa04360
    Pathways in cancerKEGGhsa05200
    Basal cell carcinomaKEGGhsa05217
    Proteoglycans in cancerKEGGhsa05205
    Proteoglycans in cancerKEGGko05205
    cAMP signaling pathwayKEGGhsa04024
    cAMP signaling pathwayKEGGko04024
    Hedgehog signalingKEGGhsa_M00678
    Hedgehog signalingKEGGM00678
    Signal TransductionREACTOMER-HSA-162582
    Signaling by GPCRREACTOMER-HSA-372790
    GPCR ligand bindingREACTOMER-HSA-500792
    Class B/2 (Secretin family receptors)REACTOMER-HSA-373080
    Signaling by HedgehogREACTOMER-HSA-5358351
    Hedgehog 'off' stateREACTOMER-HSA-5610787
    Hedgehog 'on' stateREACTOMER-HSA-5632684
    Ligand-receptor interactionsREACTOMER-HSA-5632681
    Activation of SMOREACTOMER-HSA-5635838

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    183919522008Genome-wide association analysis identifies 20 loci that influence adult height.322
    200108352010Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.251
    121924142002Patched acts catalytically to suppress the activity of Smoothened.246
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    163220882006Hedgehog signaling maintains resident hepatic progenitors throughout life.79
    159052002005Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas.63
    197306832009The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.59
    164190852006PTCH mutations: distribution and analyses.50
    192660772009Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.48
    254032192014Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations.44

    Citation

    Erika Lindström ; Rune Toftgœrd

    PTCH1 patched homolog 1 (Drosophila)

    Atlas Genet Cytogenet Oncol Haematol. 2000-12-01

    Online version: http://atlasgeneticsoncology.org/gene/100/ptch1

    Historical Card

    1999-01-01 PTCH1 patched homolog 1 (Drosophila) by  Jean-Loup Huret 

    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

    1997-05-01 PTCH1 patched homolog 1 (Drosophila) by  Jean-Loup Huret 

    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France