Target General Information
Target ID	T66505
Target Name	Smoothened homolog (SMO)
Gene Name	SMO
Species	Homo sapiens
UniProt ID	SMO_HUMAN
Sequence	MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL MDADSDF [Homo sapiens]
Drug and Corresponding Resistance Mutations
Mutation Info	Missense: A459V
Drugs	Drug Name Vismodegib Drug Info [5] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 3 out of 12 patients
	Drug Name Vismodegib Drug Info [5] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 3 out of 12 patients
Mutation Info	Missense: C469Y
Drugs	Drug Name Vismodegib Drug Info [5] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 12 patients
	Drug Name Vismodegib Drug Info [5] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 12 patients
Mutation Info	Missense: D473G
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 6 out of 14 patients
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 6 out of 14 patients
Mutation Info	Missense: D473H
Drugs	Drug Name Gdc-0449 Drug Info [1] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Gdc-0449 Drug Info [1] Targeted Disease Basal Cell Carcinoma
	Drug Name Saridegib Drug Info [6]
Mutation Info	Missense: D473N
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 30 patients
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 30 patients
Mutation Info	Missense: D473Y
Drugs	Drug Name Vismodegib Drug Info [2] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Vismodegib Drug Info [2] Targeted Disease Basal Cell Carcinoma
Mutation Info	Missense: F460L
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 30 patients
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 30 patients
Mutation Info	Missense: G497W
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma
Mutation Info	Missense: H231R
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 2 out of 30 patients
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 2 out of 30 patients
Mutation Info	Missense: L412F
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma
Mutation Info	Missense: Q477E
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 30 patients
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 30 patients
Mutation Info	Missense: S533N
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma
Mutation Info	Missense: T241M
Drugs	Drug Name Vismodegib Drug Info [5] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 12 patients
	Drug Name Vismodegib Drug Info [5] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 12 patients
Mutation Info	Missense: V321A
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 1 out of 30 patients
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 1 out of 30 patients
Mutation Info	Missense: V321M
Drugs	Drug Name Vismodegib Drug Info [4], [5] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 2 out of 12 patients
	Drug Name Vismodegib Drug Info [4], [5] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 2 out of 12 patients
Mutation Info	Missense: W281C
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 2 out of 30 patients
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 2 out of 30 patients
Mutation Info	Missense: W281L
Drugs	Drug Name Vismodegib Drug Info [4] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma
	Drug Name Vismodegib Drug Info [4] Targeted Disease Basal Cell Carcinoma
Mutation Info	Missense: W535L
Drugs	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 4 out of 30 patients
	Drug Name Vismodegib Drug Info [2], [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 4 out of 30 patients
Mutation Info	Missense: W535R
Drugs	Drug Name Vismodegib Drug Info [3] Targeted Disease Primitive Neuroectodermal Tumour Medulloblastoma Mutation Prevalence 4 out of 30 patients
	Drug Name Vismodegib Drug Info [3] Targeted Disease Basal Cell Carcinoma Mutation Prevalence 4 out of 30 patients
References
REF 1	Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009 Oct 23;326(5952):572-4.
REF 2	Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma. Mol Oncol. 2015 Feb;9(2):389-97.
REF 3	Smoothened variants explain the majority of drug resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):342-53.
REF 4	Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma. J Am Acad Dermatol. 2014 Nov;71(5):1005-8.
REF 5	Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):327-41.
REF 6	Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7859-64.

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