Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

STIL (SCL/TAL1 interrupting locus)

Written2005-10Asher Castiel, Shai Izraeli
Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)SIL
TAL1 (SCL) interrupting locus
HGNC (Hugo) STIL
HGNC Alias symbMCPH7
HGNC Previous nameSIL
HGNC Previous nameTAL1 (SCL) interrupting locus
 SCL/TAL1 interrupting locus
LocusID (NCBI) 6491
Atlas_Id 524
Location 1p33  [Link to chromosome band 1p33]
Location_base_pair Starts at 47250139 and ends at 47314147 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping STIL.png]
Local_order UMP-CMPK (47511608-47556531);SIL (47427869-47491842); TAL1 (47393984-47407363)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATPIF1 (1p35.3)::STIL (1p33)STIL (1p33)::TAL1 (1p33)STIL (1p33)::TLX3 (5q35.1)
TAL1 (1p33)::STIL (1p33)
Note 47,427,869 bp from pter; End: 47,491,842 bp from pter; Size: 63,973 bases; Orientation: minus strand

DNA/RNA

 
  Genomic structure of SIL. EcoRI sites (R) are indicated. Exons are as shown; the smaller exons are not drawn to scale.
Description 18 exons distributed over 70 kb. 5' portion of the gene demonstrating alternate exon utilization.

Protein

Description 1287 amino acids, 148KDa protein which is highly conserved in vertebrates only. No homologies to known protein motifs except for conserved Serin/Threonine phosporylation sites.
Expression SIL is an immediate early gene, with ubiquitous expression in proliferating cells and during early embryonic development. SIL protein levels peak during mitosis and are degraded on transition to G1. SIL is phosphorylated in mitosis. It is expressed in multiple cancers. In lung cancer its expression correlates with the expression of mitotic checkpoint genes
Localisation Cytosolic protein
Function SIL knockout mouse embryos die in utero displaying holopresencephaly, randomized left/right asymmetry and marked apoptosis of the neural folds. Genetic evidence showed that SIL is required for the Sonic Hedgehog response pathway. SIL phosphorylation and interactions with PIN1 is required for maintenance of the mitotic checkpoint.
Homology There is no homology to other known proteins.

Mutations

Note No mutations were found in families with hereditary holoprosencephaly.

Implicated in

Note
  
Entity SIL-TAL1(SCL) fusion.
Note A submicroscopic deletions fuses the promoter of SIL to TAL1 to induce an abnormal expression of TAL1.
Disease T-cell ALL. This TAL1-SIL fusion transcript is found in approximately 25% of T-ALL patients.
Cytogenetics Normal karyotype.
Hybrid/Mutated Gene the promoter region of the SCL gene, a hematopoietic transcription factor, and the coding region of the SIL gene are deleted. The molecular result of this SIL/SCL rearrangement is an interstitial deletion on chromosome 1 that juxtaposes the 5' portion of the SIL gene to the coding region of the SCL gene. A SIL/SCL fusion mRNA is produced, with SIL exon 1 splicing to SCL exon 3 in a head-to-tail fashion. Because these are both 5' untranslated region (UTR) exons, the net result is that SIL promoter and enhancer elements drive the expression of a full length SCL gene product.
 
Schematic representation of SIL/SCL fusion mRNA. The germ line SIL (solid boxes) and SCL (open boxes) genomic structures are shown. The deletion breakpoints are indicated with arrows. The SIL/SCL genomic rearrangement is indicated below. The SIL/SCL fusion mRNA is formed by SIL exon 1 (solid box) splicing to SCL exon 3 (open box) in a head-to-tail fashion.
  
  
Entity SIL overexpression in lung cancer.
Note SIL is also overexpressed in various solid tumors (melanoma, lymphoma, ovary cancer, breast cancer colon cancer lung and prostate cancer) and leukemic cell lines (Dami-acute megakaryocytic, and K562- erythroid blast crisis of chronic myeloid leukemia).
Disease High expression in non- small cell lung cancer (NSCLC). In addition, high expression levels in lung adenocarcinoma, lung squamous carcinoma and lung small cell carcinoma.
Prognosis SIL expression is associated with cell proliferation. In lung cancer, SIL overexpression is correlated with high mitotic activity.
  

Bibliography

Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia.
Aplan PD, Lombardi DP, Reaman GH, Sather HN, Hammond GD, Kirsch IR
Blood. 1992 ; 79 (5) : 1327-1333.
PMID 1311214
 
Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint.
Campaner S, Kaldis P, Izraeli S, Kirsch IR
Molecular and cellular biology. 2005 ; 25 (15) : 6660-6672.
PMID 16024801
 
Isolation and characterization of a human novel RAB (RAB39B) gene.
Cheng H, Ma Y, Ni X, Jiang M, Guo L, Ying K, Xie Y, Mao Y
Cytogenetic and genome research. 2002 ; 97 (1-2) : 72-75.
PMID 12438742
 
Cloning and characterization of the SIL promoter.
Colaizzo-Anas T, Aplan PD
Biochimica et biophysica acta. 2003 ; 1625 (2) : 207-213.
PMID 12531481
 
Sil overexpression in lung cancer characterizes tumors with increased mitotic activity.
Erez A, Perelman M, Hewitt SM, Cojacaru G, Goldberg I, Shahar I, Yaron P, Muler I, Campaner S, Amariglio N, Rechavi G, Kirsch IR, Krupsky M, Kaminski N, Izraeli S
Oncogene. 2004 ; 23 (31) : 5371-5377.
PMID 15107824
 
Expression of the SIL gene is correlated with growth induction and cellular proliferation.
Izraeli S, Colaizzo-Anas T, Bertness VL, Mani K, Aplan PD, Kirsch IR
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1997 ; 8 (11) : 1171-1179.
PMID 9372240
 
Genetic evidence that Sil is required for the Sonic Hedgehog response pathway.
Izraeli S, Lowe LA, Bertness VL, Campaner S, Hahn H, Kirsch IR, Kuehn MR
Genesis (New York, N.Y. : 2000). 2001 ; 31 (2) : 72-77.
PMID 11668681
 

Citation

This paper should be referenced as such :
Castiel, A ; Izraeli, S
SIL (SCL/TAL1 interrupting locus)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):97-99.
Free journal version : [ pdf ]   [ DOI ]


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  del(11)(p12p13) LMO2
Pediatric T-Cell Acute Lymphoblastic Leukemia
TAL1 (1p32) deletion in lymphoid malignancies
T-lineage acute lymphoblastic leukemia (T-ALL)


External links

 

Nomenclature
HGNC (Hugo)STIL   10879
Cards
AtlasSILID524ch1p32
Atlas Explorer : (Salamanque)STIL
Entrez_Gene (NCBI)STIL    STIL centriolar assembly protein
AliasesMCPH7; SIL
GeneCards (Weizmann)STIL
Ensembl hg19 (Hinxton)ENSG00000123473 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000123473 [Gene_View]  ENSG00000123473 [Sequence]  chr1:47250139-47314147 [Contig_View]  STIL [Vega]
ICGC DataPortalENSG00000123473
TCGA cBioPortalSTIL
AceView (NCBI)STIL
Genatlas (Paris)STIL
SOURCE (Princeton)STIL
Genetics Home Reference (NIH)STIL
Genomic and cartography
GoldenPath hg38 (UCSC)STIL  -     chr1:47250139-47314147 -  1p33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)STIL  -     1p33   [Description]    (hg19-Feb_2009)
GoldenPathSTIL - 1p33 [CytoView hg19]  STIL - 1p33 [CytoView hg38]
ImmunoBaseENSG00000123473
Genome Data Viewer NCBISTIL [Mapview hg19]  
OMIM181590   612703   
Gene and transcription
Genbank (Entrez)AA897748 AK098445 AK128406 AK307519 BC053615
RefSeq transcript (Entrez)NM_001048166 NM_001282936 NM_001282937 NM_001282938 NM_001282939 NM_001377417 NM_003035
Consensus coding sequences : CCDS (NCBI)STIL
Gene ExpressionSTIL [ NCBI-GEO ]   STIL [ EBI - ARRAY_EXPRESS ]   STIL [ SEEK ]   STIL [ MEM ]
Gene Expression Viewer (FireBrowse)STIL [ Firebrowse - Broad ]
GenevisibleExpression of STIL in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6491
GTEX Portal (Tissue expression)STIL
Human Protein AtlasENSG00000123473-STIL [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15468   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15468  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15468
PhosPhoSitePlusQ15468
Domains : Interpro (EBI)Sil   
Domain families : Pfam (Sanger)STIL_N (PF15253)   
Domain families : Pfam (NCBI)pfam15253   
Conserved Domain (NCBI)STIL
PDB (RSDB)4YYP    5LHW    5LHZ   
PDB Europe4YYP    5LHW    5LHZ   
PDB (PDBSum)4YYP    5LHW    5LHZ   
PDB (IMB)4YYP    5LHW    5LHZ   
Structural Biology KnowledgeBase4YYP    5LHW    5LHZ   
SCOP (Structural Classification of Proteins)4YYP    5LHW    5LHZ   
CATH (Classification of proteins structures)4YYP    5LHW    5LHZ   
SuperfamilyQ15468
AlphaFold pdb e-kbQ15468   
Human Protein Atlas [tissue]ENSG00000123473-STIL [tissue]
HPRD01627
Protein Interaction databases
DIP (DOE-UCLA)Q15468
IntAct (EBI)Q15468
Complex Portal (EBI)Q15468 CPX-1159 CPAP-STIL complex
BioGRIDSTIL
STRING (EMBL)STIL
ZODIACSTIL
Ontologies - Pathways
QuickGOQ15468
Ontology : AmiGOembryonic axis specification  in utero embryonic development  neural tube closure  heart looping  protein binding  cytoplasm  centrosome  centrosome  centriole  centriole  cytosol  mitotic spindle organization  mitotic spindle organization  smoothened signaling pathway  smoothened signaling pathway  determination of left/right symmetry  neural tube development  forebrain development  notochord development  floor plate development  multicellular organism growth  identical protein binding  negative regulation of apoptotic process  regulation of centriole replication  positive regulation of centriole replication  centrosome duplication  centrosome duplication  centrosome duplication  protein localization to centrosome  protein localization to centrosome  procentriole replication complex  positive regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBIembryonic axis specification  in utero embryonic development  neural tube closure  heart looping  protein binding  cytoplasm  centrosome  centrosome  centriole  centriole  cytosol  mitotic spindle organization  mitotic spindle organization  smoothened signaling pathway  smoothened signaling pathway  determination of left/right symmetry  neural tube development  forebrain development  notochord development  floor plate development  multicellular organism growth  identical protein binding  negative regulation of apoptotic process  regulation of centriole replication  positive regulation of centriole replication  centrosome duplication  centrosome duplication  centrosome duplication  protein localization to centrosome  protein localization to centrosome  procentriole replication complex  positive regulation of G1/S transition of mitotic cell cycle  
NDEx NetworkSTIL
Atlas of Cancer Signalling NetworkSTIL
Wikipedia pathwaysSTIL
Orthology - Evolution
OrthoDB6491
GeneTree (enSembl)ENSG00000123473
Phylogenetic Trees/Animal Genes : TreeFamSTIL
Homologs : HomoloGeneSTIL
Homology/Alignments : Family Browser (UCSC)STIL
Gene fusions - Rearrangements
Fusion : COSMICSTIL [1p33]  -  TAL1 [1p33]  [fusion_2150]  [fusion_2151]  [fusion_2152]  [fusion_2153]  [fusion_2154]  [fusion_2155]  [fusion_2156]  
[fusion_2157]  [fusion_2158]  [fusion_2159]  [fusion_2160]  [fusion_2161]  [fusion_2162]  [fusion_2163]  [fusion_2164]  [fusion_2165]  [fusion_2166]  
[fusion_2167]  [fusion_2168]  [fusion_2169]  [fusion_2170]  [fusion_2171]  [fusion_2172]  [fusion_2173]  [fusion_2174]  [fusion_2175]  [fusion_2176]  
[fusion_2177]  [fusion_2178]  [fusion_2179]  [fusion_2180]  [fusion_2181]  [fusion_2183]  [fusion_2184]  [fusion_2185]  [fusion_2186]  [fusion_2187]  
[fusion_2188]  [fusion_2189]  [fusion_2190]  [fusion_2191]  [fusion_2192]  [fusion_2193]  [fusion_2194]  [fusion_2195]  [fusion_2196]  [fusion_2197]  
[fusion_2198]  [fusion_2199]  [fusion_2200]  [fusion_2201]  [fusion_2202]  [fusion_2203]  [fusion_2204]  [fusion_2205]  [fusion_2206]  [fusion_2207]  
[fusion_2208]  [fusion_2209]  [fusion_2210]  [fusion_2211]  [fusion_2212]  [fusion_2213]  [fusion_2214]  [fusion_2215]  [fusion_2216]  [fusion_2219]  
[fusion_2220]  [fusion_2221]  [fusion_2222]  [fusion_2223]  [fusion_2224]  [fusion_2225]  [fusion_2226]  [fusion_2227]  [fusion_2228]  [fusion_2229]  
[fusion_2230]  [fusion_2231]  [fusion_2232]  [fusion_2242]  
Fusion : FusionHubATPIF1--STIL    KIAA0922--STIL    MAST2--STIL    NRD1--STIL    STIL--MAST2    STIL--TAL1    STIL--TRMT11    TAL1--STIL   
Fusion : QuiverSTIL
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSTIL [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)STIL
dbVarSTIL
ClinVarSTIL
MonarchSTIL
1000_GenomesSTIL 
Exome Variant ServerSTIL
GNOMAD BrowserENSG00000123473
Varsome BrowserSTIL
ACMGSTIL variants
VarityQ15468
Genomic Variants (DGV)STIL [DGVbeta]
DECIPHERSTIL [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSTIL 
Mutations
ICGC Data PortalSTIL 
TCGA Data PortalSTIL 
Broad Tumor PortalSTIL
OASIS PortalSTIL [ Somatic mutations - Copy number]
Cancer Gene: CensusSTIL 
Somatic Mutations in Cancer : COSMICSTIL  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSTIL
Mutations and Diseases : HGMDSTIL
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaSTIL
DgiDB (Drug Gene Interaction Database)STIL
DoCM (Curated mutations)STIL
CIViC (Clinical Interpretations of Variants in Cancer)STIL
OncoKBSTIL
NCG (London)STIL
Cancer3DSTIL
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM181590    612703   
Orphanet732    20435    18904    12486    12484    12485    14434   
DisGeNETSTIL
MedgenSTIL
Genetic Testing Registry STIL
NextProtQ15468 [Medical]
GENETestsSTIL
Target ValidationSTIL
Huge Navigator STIL [HugePedia]
ClinGenSTIL
Clinical trials, drugs, therapy
MyCancerGenomeSTIL
Protein Interactions : CTDSTIL
Pharm GKB GenePA35780
PharosQ15468
Clinical trialSTIL
Miscellaneous
canSAR (ICR)STIL
HarmonizomeSTIL
ARCHS4STIL
DataMed IndexSTIL
Probes
Litterature
PubMed86 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXSTIL
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Jan 20 14:17:27 CET 2022

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.