PTCH1

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.

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 hedgehog binds PTCH1, smoothened is released and signals cell proliferation.

Clinical significance

Mutations of this gene have been associated with nevoid basal cell carcinoma syndrome (AKA Gorlin's 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.

Mutations in PTCH1 cause Gorlin syndrome and mutations have also been found in holoprosencephaly patients. 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. In addition association between SNPs in or near PTCH1 have been found to be associated with nonsyndromic cleft lip and palate. Mutations in PTCH1 are also associated with medulloblastoma.

Further reading

• Villavicencio EH, Walterhouse DO, Iannaccone PM (2000). "The sonic hedgehog-patched-gli pathway in human development and disease". Am. J. Hum. Genet. 67 (5): 1047–54. doi:10.1016/S0002-9297(07)62934-6. PMC 1288546. PMID 11001584.
• Corcoran RB, Scott MP (2002). "A mouse model for medulloblastoma and basal cell nevus syndrome". J. Neurooncol. 53 (3): 307–18. doi:10.1023/A:1012260318979. PMID 11718263.
• Lindström E, Shimokawa T, Toftgård R, Zaphiropoulos PG (2006). "PTCH mutations: distribution and analyses". Hum. Mutat. 27 (3): 215–9. doi:10.1002/humu.20296. PMID 16419085.
• Gailani MR, Bale SJ, Leffell DJ, et al. (1992). "Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9". Cell. 69 (1): 111–7. doi:10.1016/0092-8674(92)90122-S. PMID 1348213.
• Hahn H, Christiansen J, Wicking C, et al. (1996). "A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities". J. Biol. Chem. 271 (21): 12125–8. doi:10.1074/jbc.271.18.10941. PMID 8647801.
• Hahn H, Wicking C, Zaphiropoulous PG, et al. (1996). "Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome". Cell. 85 (6): 841–51. doi:10.1016/S0092-8674(00)81268-4. PMID 8681379.
• Gailani MR, Ståhle-Bäckdahl M, Leffell DJ, et al. (1996). "The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas". Nat. Genet. 14 (1): 78–81. doi:10.1038/ng0996-78. PMID 8782823.
• Chidambaram A, Goldstein AM, Gailani MR, et al. (1996). "Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients". Cancer Res. 56 (20): 4599–601. PMID 8840969.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Stone DM, Hynes M, Armanini M, et al. (1996). "The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog". Nature. 384 (6605): 129–34. doi:10.1038/384129a0. PMID 8906787.
• Wicking C, Shanley S, Smyth I, et al. (1997). "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". Am. J. Hum. Genet. 60 (1): 21–6. PMC 1712561. PMID 8981943.
• Lench NJ, Telford EA, High AS, et al. (1997). "Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome". Hum. Genet. 100 (5–6): 497–502. doi:10.1007/s004390050541. PMID 9341860.
• Aszterbaum M, Rothman A, Johnson RL, et al. (1998). "Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome". J. Invest. Dermatol. 110 (6): 885–8. doi:10.1046/j.1523-1747.1998.00222.x. PMID 9620294.
• Carpenter D, Stone DM, Brush J, et al. (1998). "Characterization of two patched receptors for the vertebrate hedgehog protein family". Proc. Natl. Acad. Sci. U.S.A. 95 (23): 13630–4. doi:10.1073/pnas.95.23.13630. PMC 24870. PMID 9811851.
• Liu JH, Wei S, Burnette PK, et al. (1999). "Functional association of TGF-beta receptor II with cyclin B.". Oncogene. 18 (1): 269–75. doi:10.1038/sj.onc.1202263. PMID 9926943.
• Hasenpusch-Theil K, Bataille V, Laehdetie J, et al. (1999). "Gorlin syndrome: identification of 4 novel germ-line mutations of the human patched (PTCH) gene. Mutations in brief no. 137. Online". Hum. Mutat. 11 (6): 480. doi:10.1002/(SICI)1098-1004(1998)11:6<480::AID-HUMU9>3.0.CO;2-4. PMID 10200051.
• Dong J, Gailani MR, Pomeroy SL, et al. (2000). "Identification of PATCHED mutations in medulloblastomas by direct sequencing". Hum. Mutat. 16 (1): 89–90. doi:10.1002/1098-1004(200007)16:1<89::AID-HUMU18>3.0.CO;2-7. PMID 10874314.
• Reifenberger J, Arnold N, Kiechle M, et al. (2001). "Coincident PTCH and BRCA1 germline mutations in a patient with nevoid basal cell carcinoma syndrome and familial breast cancer". J. Invest. Dermatol. 116 (3): 472–4. doi:10.1046/j.1523-1747.2001.01279-2.x. PMID 11231326.

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.