PTCH1

Identity

Other names	PTC, but this term was confusing with PTC/PKA
	PTCH
	patched
HGNC	PTCH1
Location	9q22.3
Location_base_pair	Starts at 97245085 and ends at 97310652 bp from pter ( according to hg18-Mar_2006).
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

External links

	Nomenclature
HGNC	PTCH1   9585
Entrez_Gene	PTCH1  5727  patched homolog 1 (Drosophila)
	Cards
Atlas	PTCH100
GeneCards	PTCH1
Ensembl	ENSG00000185920 [Gene_View]  PTCH1 [Vega]
Genatlas	PTCH1
	Genomic and cartography
GoldenPath	PTCH1  -  9q22.3   chr9:97245085-97310652 -  9q22.1-q31   [Description]    (hg18-Mar_2006)
Ensembl	PTCH1 - 9q22.1-q31 [CytoView]
NCBI	Mapview
OMIM	109400 Disease map [OMIM]
OMIM	155255 Disease map [OMIM]
OMIM	601309 Disease map [OMIM]
OMIM	605462 Disease map [OMIM]
OMIM	610828 Disease map [OMIM]
HomoloGene	PTCH1
	Gene and transcription
Genbank	AB189436 [ ENTREZ ]
Genbank	AB189437 [ ENTREZ ]
Genbank	AB189438 [ ENTREZ ]
Genbank	AB189439 [ ENTREZ ]
Genbank	AB189440 [ ENTREZ ]
RefSeq	NM_000264 [ SRS ]    NM_000264 [ ENTREZ ]
RefSeq	NM_001083602 [ SRS ]    NM_001083602 [ ENTREZ ]
RefSeq	NM_001083603 [ SRS ]    NM_001083603 [ ENTREZ ]
RefSeq	NM_001083604 [ SRS ]    NM_001083604 [ ENTREZ ]
RefSeq	NM_001083605 [ SRS ]    NM_001083605 [ ENTREZ ]
RefSeq	NM_001083606 [ SRS ]    NM_001083606 [ ENTREZ ]
RefSeq	NM_001083607 [ SRS ]    NM_001083607 [ ENTREZ ]
RefSeq	AC_000052 [ SRS ]    AC_000052 [ ENTREZ ]
RefSeq	AC_000141 [ SRS ]    AC_000141 [ ENTREZ ]
RefSeq	NC_000009 [ SRS ]    NC_000009 [ ENTREZ ]
RefSeq	NG_007664 [ SRS ]    NG_007664 [ ENTREZ ]
RefSeq	NT_008470 [ SRS ]    NT_008470 [ ENTREZ ]
RefSeq	NW_001839235 [ SRS ]    NW_001839235 [ ENTREZ ]
RefSeq	NW_924506 [ SRS ]    NW_924506 [ ENTREZ ]
CCDS	PTCH1 CCDS - NCBI
AceView	PTCH1 AceView - NCBI
Unigene	Hs.638946 [ SRS ]    Hs.638946 [ NCBI ]
Fast-db	11290 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q13635 [ SRS]    Q13635 [ EXPASY ]     Q13635 [ INTERPRO ]     Q13635 [ UNIPROT ] Q13635 [ VarSplice FASTA ]
Prosite	PS50156 SSD [ SRS ]    PS50156 SSD [ Expasy ]
Interpro	IPR003392 Patched [ SRS ]    IPR003392 Patched [ EBI ]
Interpro	IPR000731 SSD_5TM [ SRS ]    IPR000731 SSD_5TM [ EBI ]
Interpro	IPR004766 TM_rcpt_patched [ SRS ]    IPR004766 TM_rcpt_patched [ EBI ]
CluSTr	Q13635
Pfam	PF02460 Patched [ SRS ]    PF02460 Patched [ Sanger ]    pfam02460 [ NCBI-CDD ]
Blocks	Q13635
HPRD	03200
	Protein Interaction databases
DIP	Q13635
IntAct	Q13635
	Polymorphism : SNP, mutations, diseases
OMIM	109400    [ map ]
OMIM	155255    [ map ]
OMIM	601309    [ map ]
OMIM	605462    [ map ]
OMIM	610828    [ map ]
GENETests	109400
GENETests	155255
GENETests	601309
GENETests	605462
GENETests	610828
SNP	PTCH1 [dbSNP-NCBI]
SNP	NM_000264 [SNP-NCI]
SNP	NM_001083602 [SNP-NCI]
SNP	NM_001083603 [SNP-NCI]
SNP	NM_001083604 [SNP-NCI]
SNP	NM_001083605 [SNP-NCI]
SNP	NM_001083606 [SNP-NCI]
SNP	NM_001083607 [SNP-NCI]
SNP	PTCH1 [GeneSNPs - Utah]  PTCH1] [HGBASE - SRS]
HAPMAP	PTCH1 [HAPMAP]
COSMIC	PTCH1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	PTCH1
Genetic Association	PTCH1
CDC HuGE	PTCH1
	General knowledge
Family Browser	PTCH1 [UCSC Family Browser]
SOURCE	NM_000264
SOURCE	NM_001083602
SOURCE	NM_001083603
SOURCE	NM_001083604
SOURCE	NM_001083605
SOURCE	NM_001083606
SOURCE	NM_001083607
SMD	Hs.638946
SAGE	Hs.638946
GO	receptor activity [Amigo]  receptor activity
GO	protein binding [Amigo]  protein binding
GO	integral to plasma membrane [Amigo]  integral to plasma membrane
GO	signal transduction [Amigo]  signal transduction
GO	hedgehog receptor activity [Amigo]  hedgehog receptor activity
GO	cell proliferation [Amigo]  cell proliferation
GO	regulation of smoothened signaling pathway [Amigo]  regulation of smoothened signaling pathway
GO	organ morphogenesis [Amigo]  organ morphogenesis
GO	dorsal/ventral pattern formation [Amigo]  dorsal/ventral pattern formation
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
GO	protein processing [Amigo]  protein processing
GO	embryonic limb morphogenesis [Amigo]  embryonic limb morphogenesis
GO	negative regulation of multicellular organism growth [Amigo]  negative regulation of multicellular organism growth
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
BIOCARTA	Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle    [Genes]
BIOCARTA	Sonic Hedgehog (Shh) Pathway    [Genes]
KEGG	Hedgehog signaling pathway
PubGene	PTCH1
TreeFam	PTCH1
CTD	5727 [Comparative ToxicoGenomics Database]
	Other databases
Other database	Locus specific database; PTCH Mutation Database
	Probes
Probe	PTCH1 Related clones (RZPD - Berlin)
	PubMed
PubMed	78 Pubmed reference(s) in Entrez

Bibliography

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Nature. 1994 ; 368 (6468) : 208-214.

PMID 8145818

The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.

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The EMBO journal. 1994 ; 13 (1) : 71-82.

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The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.

Gailani MR, Stˆ€hle-Bˆ§ckdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Undˆ©n AB, Dean M, Brash DE, Bale AE, Toftgˆ€rd R

Nature genetics. 1996 ; 14 (1) : 78-81.

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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

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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

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Human homolog of patched, a candidate gene for the basal cell nevus syndrome.

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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.

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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, Lindstrˆm E, Hemminki K, Toftgˆ€rd 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.

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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.

Daya-Grosjean L, Sarasin A

Mutation research. 2000 ; 450 (1-2) : 193-199.

PMID 10838143

UV mutation signature in tumor suppressor genes involved in skin carcinogenesis in xeroderma pigmentosum patients.

D'Errico M, Calcagnile A, Canzona F, Didona B, Posteraro P, Cavalieri R, Corona R, Vorechovsky I, Nardo T, Stefanini M, Dogliotti E

Oncogene. 2000 ; 19 (3) : 463-467.

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.

Evans T Boonchai W Shanley S Smyth I Gillies S Georgas K Wainwright B ChenevixTrench G Wicking C

Hum Mut. 2000 ; 16 (numero 1) : 43-48.

PMID 20334495

Hedgehog signaling in animal development and human disease.

Bailey EC, Scott MP, Johnson RL

Ernst Schering Research Foundation workshop. 2000 : 211-235.

PMID 10943312

Hedgehog signalling in cancer.

Toftgˆ€rd R

Cellular and molecular life sciences : CMLS. 2000 ; 57 (12) : 1720-1731.

PMID 11130178

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	05-1997	Jean-Loup Huret
		-
Updated	01-1999	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	12-2000	Erika 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 :

Huret JL . PTCH1. Atlas Genet Cytogenet Oncol Haematol. May 1997 . URL : http://AtlasGeneticsOncology.org/Genes/PTCH100.html

Huret JL . PTCH1. Atlas Genet Cytogenet Oncol Haematol. January 1999 . URL : http://AtlasGeneticsOncology.org/Genes/PTCH100.html

Lindström E, Toftgård R . PTCH1. Atlas Genet Cytogenet Oncol Haematol. December 2000 . URL : http://AtlasGeneticsOncology.org/Genes/PTCH100.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:28:03 2008