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mutLBSgeneDB |
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| Gene summary for SMO |
 Gene summary |
| Basic gene Info. | Gene symbol | SMO |
| Gene name | smoothened, frizzled class receptor | |
| Synonyms | FZD11|Gx|SMOH | |
| Cytomap | UCSC genome browser: 7q32.3 | |
| Type of gene | protein-coding | |
| RefGenes | NM_005631.4, | |
| Description | frizzled family member 11protein Gxseven transmembrane helix receptorsmoothened homologsmoothened, frizzled family receptorsmoothened, seven transmembrane spanning receptor | |
| Modification date | 20141207 | |
| dbXrefs | MIM : 601500 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000128602 | ||
| HPRD : 03294 | ||
| Vega : OTTHUMG00000158421 | ||
| Protein | UniProt: Q99835 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_SMO | |
| BioGPS: 6608 | ||
| Pathway | NCI Pathway Interaction Database: SMO | |
| KEGG: SMO | ||
| REACTOME: SMO | ||
| Pathway Commons: SMO | ||
| Context | iHOP: SMO | |
| ligand binding site mutation search in PubMed: SMO | ||
| UCL Cancer Institute: SMO | ||
| Assigned class in mutLBSgeneDB | A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes. | |
| References showing study about ligand binding site mutation for SMO. | 1. "Chenna V, Hu C, Pramanik D, Aftab BT, Karikari C, Campbell NR, Hong SM, Zhao M, Rudek MA, Khan SR, Rudin CM, Maitra A. A polymeric nanoparticle encapsulated small-molecule inhibitor of Hedgehog signaling (NanoHHI) bypasses secondary mutational resistance to Smoothened antagonists. Mol Cancer Ther. 2012 Jan;11(1):165-73. doi: 10.1158/1535-7163.MCT-11-0341. Epub 2011 Oct 25." 22027695 | |
| Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
| GO ID | GO Term | PubMed ID |
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| Ligand binding site mutations for SMO |
| Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.)  : non-synonymous mutation on LBS, Circle size denotes number of samples. |
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| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | W281 | G280C | BLCA | 1 | T466 | T466N | LUAD | 1 | R400 | R398Q | SKCM | 1 | T528 | T528A | SKCM | 1 | L325 | L325P | SKCM | 1 | Y394 | Y394H | STAD | 1 | E481 | R482C | STAD | 1 | H470,T466 | S468G | STAD | 1 | I408 | G409S | STAD | 1 | L303 | L303I | UCEC | 1 |
| cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma. |
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| Protein structure related information for SMO |
| Relative protein structure stability change (ΔΔE) using Mupro 1.1 Mupro score denotes assessment of the effect of mutations on thermodynamic stability. (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability) |
 : nsSNV at non-LBS : nsSNV at LBS |
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| nsSNVs sorted by the relative stability change of protein structure by each mutation Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene. |
| LBS | AAchange of nsSNV | Relative stability change | L325 | L325P | -1.6034697 | R400 | R398Q | -1.4454297 | Y394 | Y394H | -1.3306592 | T466 | T466N | -1.270878 | E481 | R482C | -1.2502103 | T466 | S468G | -0.97524719 | H470 | S468G | -0.97524719 | L303 | L303I | -0.85794531 | I408 | G409S | -0.76317651 | T528 | T528A | -0.36834714 | W281 | G280C | -0.24909044 |
| (MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132) |
| Structure image for SMO from PDB |
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| Differential gene expression and gene-gene network for SMO |
| Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types |
| Differential co-expressed gene network based on protein-protein interaction data (CePIN) |
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| Phenotype information for SMO |
| Gene level disease information (DisGeNet) |
| Disease ID | Disease name | # PubMed | Association type |
| umls:C0007117 | Carcinoma, Basal Cell | 3 | AlteredExpression, Biomarker, GeneticVariation |
| umls:C0025286 | Meningioma | 2 | Biomarker, GeneticVariation |
| umls:C0206663 | Neuroectodermal Tumors, Primitive | 1 | Biomarker |
| umls:C0002448 | Ameloblastoma | 1 | Biomarker |
| umls:C0006118 | Brain Neoplasms | 1 | Biomarker |
| umls:C0022360 | Jaw Abnormalities | 1 | Biomarker |
| umls:C0023487 | Leukemia, Promyelocytic, Acute | 1 | Biomarker |
| umls:C0024954 | Maxillary Neoplasms | 1 | Biomarker |
| umls:C0037286 | Skin Neoplasms | 1 | Biomarker |
| Mutation level pathogenic information (ClinVar annotation) |
| Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
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| Pharmacological information for SMO |
| Gene expression profile of anticancer drug treated cell-lines (CCLE) Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient. |
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| Gene-centered drug-gene interaction network |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Approved|investigational | DB01047 | Fluocinonide | Small molecule |  |
| Approved|investigational|withdrawn | DB06786 | Halcinonide | Small molecule |  |
| Approved | DB08828 | Vismodegib | Small molecule |  |
| Approved|investigational | DB09143 | Sonidegib | Small molecule |  |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of SMO go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | SG8 | 3-CHLORO-4,7-DIFLUORO-N-[TRANS-4-(METHYLAMINO) CYCLOHEXYL]-N-[3-(PYRIDIN-4-YL)BENZYL]-1- BENZOTHIOPHENE-2-CARBOXAMIDE | 4qin | A | L303 Y394 H470 E481 | CY8 | CYCLOPAMINE | (3ALPHA,8ALPHA,14BETA,22S,23R)-17,23-EPOXYVERATRAMAN-3- OL | 4o9r | A | L303 Y394 R400 E481 | SNT | SANT-1 | (E)-N-(4-BENZYLPIPERAZIN-1-YL)-1-(3,5-DIMETHYL-1- PHENYL-1H-PYRAZOL-4-YL)METHANIMINE | 4n4w | A | W281 L325 Y394 I408 T466 H470 T528 | 1KS | 4-FLUORO-N-METHYL-N-{1-[4-(1-METHYL-1H-PYRAZOL-5-YL) PHTHALAZIN-1-YL]PIPERIDIN-4-YL}-2-(TRIFLUOROMETHYL) BENZAMIDE | 4jkv | A | W281 Y394 R400 E481 | 1KS | 4-FLUORO-N-METHYL-N-{1-[4-(1-METHYL-1H-PYRAZOL-5-YL) PHTHALAZIN-1-YL]PIPERIDIN-4-YL}-2-(TRIFLUOROMETHYL) BENZAMIDE | 4jkv | B | W281 Y394 R400 E481 | A8T | 2-{6-[4-(4-BENZYLPHTHALAZIN-1-YL)PIPERAZIN-1- YL]PYRIDIN-3-YL}PROPAN-2-OL | 4qim | A | W281 Y394 R400 H470 |
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| Conservation information for LBS of SMO |
| Multiple alignments for Q99835 in multiple species |
| LBS | AA sequence | # species | Species | D384 | AQVDGDSVSGI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D384 | SEVDGNSIVGI | 1 | Drosophila melanogaster | D473 | SCHFYDFFNQA | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D473 | ACHVTEFRHAD | 1 | Drosophila melanogaster | E481 | NQAEWERSFRD | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E481 | HADEWAQSFRQ | 1 | Drosophila melanogaster | E518 | PSLLVEKINLF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E518 | PSVGVLQLHLL | 1 | Drosophila melanogaster | F222 | CQNPLFTEAEH | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F222 | CKDPLYTDDEH | 1 | Drosophila melanogaster | F274 | YVNACFFVGSI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F274 | YINLCFLIACV | 1 | Drosophila melanogaster | F391 | VSGICFVGYKN | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F391 | IVGICFVGYIN | 1 | Drosophila melanogaster | F484 | EWERSFRDYVL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F484 | EWAQSFRQFII | 1 | Drosophila melanogaster | G383 | VAQVDGDSVSG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G383 | FSEVDGNSIVG | 1 | Drosophila melanogaster | H470 | ITFSCHFYDFF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | H470 | VAIACHVTEFR | 1 | Drosophila melanogaster | I215 | VEGCGIQCQNP | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I215 | IEGCGVRCKDP | 1 | Drosophila melanogaster | I389 | DSVSGICFVGY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I389 | NSIVGICFVGY | 1 | Drosophila melanogaster | I408 | FVLAPIGLVLI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I408 | LLLGPLCGVIL | 1 | Drosophila melanogaster | K395 | CFVGYKNYRYR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K395 | CFVGYINHSMR | 1 | Drosophila melanogaster | L221 | QCQNPLFTEAE | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L221 | RCKDPLYTDDE | 1 | Drosophila melanogaster | L303 | DGTMRFGEPTS | 2 | Mus musculus, Rattus norvegicus | L303 | DGTMRLGEPTS | 1 | Homo sapiens | L303 | DGTLRHSEPTA | 1 | Drosophila melanogaster | L325 | IVYYALMAGVV | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L325 | LVYYFLTAGMV | 1 | Drosophila melanogaster | L522 | VEKINLFAMFG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L522 | VLQLHLLCLFS | 1 | Drosophila melanogaster | M230 | AEHQDMHSYIA | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M230 | DEHRQIHKLIG | 1 | Drosophila melanogaster | M301 | RADGTMRFGEP | 2 | Mus musculus, Rattus norvegicus | M301 | RADGTMRLGEP | 1 | Homo sapiens | M301 | RKDGTLRHSEP | 1 | Drosophila melanogaster | M326 | VYYALMAGVVW | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M326 | VYYFLTAGMVW | 1 | Drosophila melanogaster | M525 | INLFAMFGTGI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M525 | LHLLCLFSSGI | 1 | Drosophila melanogaster | N219 | GIQCQNPLFTE | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | N219 | GVRCKDPLYTD | 1 | Drosophila melanogaster | N521 | LVEKINLFAMF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | N521 | GVLQLHLLCLF | 1 | Drosophila melanogaster | P220 | IQCQNPLFTEA | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | P220 | VRCKDPLYTDD | 1 | Drosophila melanogaster | P513 | EIKNRPSLLVE | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | P513 | RIENRPSVGVL | 1 | Drosophila melanogaster | Q477 | YDFFNQAEWER | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | Q477 | TEFRHADEWAQ | 1 | Drosophila melanogaster | R400 | KNYRYRAGFVL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R400 | INHSMRAGLLL | 1 | Drosophila melanogaster | S387 | DGDSVSGICFV | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | S387 | DGNSIVGICFV | 1 | Drosophila melanogaster | T466 | GFVLITFSCHF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | T466 | VFILVAIACHV | 1 | Drosophila melanogaster | T528 | FAMFGTGIAMS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | T528 | LCLFSSGIVMS | 1 | Drosophila melanogaster | V329 | ALMAGVVWFVV | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V329 | FLTAGMVWFVF | 1 | Drosophila melanogaster | V386 | VDGDSVSGICF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V386 | VDGNSIVGICF | 1 | Drosophila melanogaster | V463 | LAFGFVLITFS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V463 | LTLVFILVAIA | 1 | Drosophila melanogaster | W281 | VGSIGWLAQFM | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | W281 | IACVGWLLQFT | 1 | Drosophila melanogaster | W480 | FNQAEWERSFR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | W480 | RHADEWAQSFR | 1 | Drosophila melanogaster | Y394 | ICFVGYKNYRY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | Y394 | ICFVGYINHSM | 1 | Drosophila melanogaster |
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