PTCH1
Template:PBB Protein patched homolog 1 is a protein that is the member of the Patched family and in humans is encoded by the PTCH1 gene.[1][2]
Function
PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. This gene functions as a tumor suppressor. The PTCH1 gene product, is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgheog binds PTCH1, smoothened is released and signals cell proliferation.
Clinical significance
Mutations of this gene have been associated with nevoid basal cell carcinoma syndrome, esophageal squamous cell carcinoma, trichoepitheliomas, transitional cell carcinomas of the bladder, as well as holoprosencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences and biological validity cannot be determined currently.[2]
Mutations in PTCH1 cause Gorlin syndrome often with a midline cleft lip[3] and mutations have also been found in holoprosencephaly patients.[4][5][6] Some of these patients present cleft lip and palate among the holoprosencephaly features, and missense variants in PTCH1 were also found in a sequencing screening of nonsyndromic cleft lip and palate patients.[7] In addition association between SNPs in or near PTCH1 have been found to be associated with nonsyndromic cleft lip and palate.[7][8] Mutations in PTCH1 are also associated with medulloblastoma.[9]
References
- ^ Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP (Aug 1996). "Human homolog of patched, a candidate gene for the basal cell nevus syndrome". Science. 272 (5268): 1668–71. doi:10.1126/science.272.5268.1668. PMID 8658145.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b "Entrez Gene: PTCH1 patched homolog 1 (Drosophila)".
- ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Ming JE, Kaupas ME, Roessler E; et al. (April 2002). "Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly". Hum. Genet. 110 (4): 297–301. doi:10.1007/s00439-002-0695-5. PMID 11941477.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Rahimov F, Ribeiro LA, de Miranda E, Richieri-Costa A, Murray JC (December 2006). "GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum?". Am. J. Med. Genet. A. 140 (23): 2571–6. doi:10.1002/ajmg.a.31370. PMID 17096318.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Ribeiro LA, Quiezi RG, Nascimento A, Bertolacini CP, Richieri-Costa A (July 2010). "Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients". Am. J. Med. Genet. A. 152A (7): 1688–94. doi:10.1002/ajmg.a.33466. PMID 20583177.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Mansilla MA, Cooper ME, Goldstein T; et al. (January 2006). "Contributions of PTCH gene variants to isolated cleft lip and palate". Cleft Palate Craniofac. J. 43 (1): 21–9. doi:10.1597/04-169R.1. PMC 2151847. PMID 16405370.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Moreno LM, Mansilla MA, Bullard SA; et al. (December 2009). "FOXE1 association with both isolated cleft lip with or without cleft palate, and isolated cleft palate". Hum. Mol. Genet. 18 (24): 4879–96. doi:10.1093/hmg/ddp444. PMC 2778374. PMID 19779022.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Jones, David T. W.; Jäger, Natalie; Kool, Marcel; Zichner, Thomas; et al. "Dissecting the genomic complexity underlying medulloblastoma". Nature. doi:10.1038/nature11284.
{{cite journal}}: Explicit use of et al. in:|author5=(help)
Further reading
External links
- GeneReviews/NCBI/NIH/UW entry on Nevoid Basal Cell Carcinoma Syndrome
- GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion
- Drosophila patched - The Interactive Fly
- PTCH1 human gene location in the UCSC Genome Browser.
- PTCH1 human gene details in the UCSC Genome Browser.
