PTCH1
In
databases:
● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
5727 or PTCH1
● Ensembl (http://www.ensembl.org/index.html):
ENSG00000185920
● UniProt (http://www.uniprot.org/):
Q13635
● OMIM (http://www.ncbi.nlm.nih.gov/omim):
601309
● GeneCards (http://www.genecards.org/): PTCH1
● HGNC (http://www.genenames.org/): 9585 or PTCH1
Gene locus:
9q22.32
Protein name:
Patched 1
Protein Size:
1447 amino acids; about 161 kDa
Function:
The protein encoded by PTCH1 acts as a
receptor for sonic hedgehog, a secreted molecule implicated in the formation of
embryonic structures and in tumorigenesis, as well as indian hedgehog and
desert hedgehog. Associates with the smoothened protein (SMO) to transduce the
hedgehog's proteins signal. PTCH1 functions as a tumor suppressor. It is
thought to have a repressive activity on cell proliferation and could play a
role in DNA maintenance, repair and/or replication, since NBCSS syndrome is a
chromosome instability syndrome.
Cancer-related alterations:
Germinal mutations lead to protein
truncation in nevoid 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 mutation
hot spot.
Somatic mutation and allele loss events
have been observed in basal cell carcinoma, in NBCCS and in sporadic basal cell
carcinoma. Mutation and allele loss have also been found in sporadic primitive
neuroectodermal tumors (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 (tumors often associated with basal cell carcinomas) and in
sporadic odontogenic keratocysts
A large majority of these somatic
mutations are substitutions. There are no mutation hot spots
Genetic alterations in PTCH1 are the cause
of basal cell nevus syndrome (BCNS) also known as Gorlin syndrome or
Gorlin-Goltz syndrome. BCNS is an autosomal dominant disease characterized by
nevoid basal cell carcinomas (NBCCS) and developmental abnormalities such as
rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In
addition, the patients suffer from a multitude of tumors like basal cell
carcinomas (BCC), fibromas of the ovaries and heart, cysts of the skin, jaws
and mesentery, as well as medulloblastomas and meningiomas. PTCH1 is also
mutated in squamous cell carcinoma (SCC).
References (open access):
Nevoid basal cell carcinoma syndrome
(Gorlin syndrome). Lo Muzio L. Orphanet J Rare Dis. 2008 Nov 25;3:32.
Gorlin syndrome or basal cell nevus
syndrome (BCNS): A case report. Shivaswamy KN, Sumathy TK, Shyamprasad AL,
Ranganathan C. Dermatol Online J. 2010 Sep 15;16(9):6.
Mechanisms of inactivation of PTCH1 gene
in nevoid basal cell carcinoma syndrome: modification of the two-hit
hypothesis. Pan S, Dong Q, Sun LS, Li TJ. Clin Cancer Res. 2010 Jan
15;16(2):442-50.
Patched1 functions as a gatekeeper by
promoting cell cycle progression. Adolphe C, Hetherington R, Ellis T,
Wainwright B. Cancer Res. 2006 Feb 15;66(4):2081-8.
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