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
  • Article Bibliography

    Pubmed IDLast YearTitleAuthors

    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
    382874792024PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.2
    384112522024PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.2
    382874792024PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.2
    384112522024PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.2
    368701162023Rs28446116 in PTCH1 is associated with non-syndromic cleft lip with or without palate in the Ningxia population, China.1
    372831072023Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome.0
    368701162023Rs28446116 in PTCH1 is associated with non-syndromic cleft lip with or without palate in the Ningxia population, China.1
    372831072023Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome.0
    348628242022Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy.2
    349907982022Inherited rare and common variants in PTCH1 and PTCH2 contributing to the predisposition to reproductive cancers.3
    352766082022Differential promoter usages of PTCH1 and down regulation of HHIP are associated with HNSCC progression.1
    353187162022Impaired Wnt/beta-catenin and protein patched homolog 1 signaling in extraocular sebaceous carcinoma: A clinical and histopathological study.0
    355691172022Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.6
    362051382022New insight into the role of PTCH1 protein in serous ovarian carcinomas.1
    348628242022Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy.2

    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/gene-explorer/teaching-explorer/hgnc

    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