PTCH1

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Patched 1
Identifiers
Symbols PTCH1 ; BCNS; HPE7; NBCCS; PTC; PTC1; PTCH; PTCH11
External IDs OMIM601309 MGI105373 HomoloGene223 GeneCards: PTCH1 Gene
RNA expression pattern
PBB GE PTCH1 209815 at tn.png
PBB GE PTCH1 208522 s at tn.png
PBB GE PTCH1 209816 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5727 19206
Ensembl ENSG00000185920 ENSMUSG00000021466
UniProt Q13635 Q61115
RefSeq (mRNA) NM_000264 NM_008957
RefSeq (protein) NP_000255 NP_032983
Location (UCSC) Chr 9:
98.21 – 98.28 Mb
Chr 13:
63.51 – 63.57 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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[edit]

  1. ^ Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH, 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. 
  2. ^ a b "Entrez Gene: PTCH1 patched homolog 1 (Drosophila)". 
  3. ^ 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. 
  4. ^ Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M (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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ a b Mansilla MA, Cooper ME, Goldstein T, Castilla EE, Lopez Camelo JS, Marazita ML, Murray JC (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. 
  8. ^ Moreno LM, Mansilla MA, Bullard SA, Cooper ME, Busch TD, Machida J, Johnson MK, Brauer D, Krahn K, Daack-Hirsch S, L'heureux J, Valencia-Ramirez C, Rivera D, López AM, Moreno MA, Hing A, Lammer EJ, Jones M, Christensen K, Lie RT, Jugessur A, Wilcox AJ, Chines P, Pugh E, Doheny K, Arcos-Burgos M, Marazita ML, Murray JC, Lidral AC (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. 
  9. ^ Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P (August 2012). "Dissecting the genomic complexity underlying medulloblastoma". Nature 488 (7409): 100–5. doi:10.1038/nature11284. PMC 3662966. PMID 22832583. 

Further reading[edit]

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