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ROS1 (ROS proto-oncogene 1 , receptor tyrosine kinase)

Written2014-01Samuel J Klempner, Sai-Hong Ou
University of California Irvine Medical Center, Orange, CA. sklempne@uci.edu; siou@uci.edu

Abstract ROS1 is proto-oncogene encoding a type I integral membrane protein with receptor tyrosine kinase (RTK) activity. ROS1 is a member of the insulin receptor family and is involved in downstream signalling processes involved in cell growth and differentiation.

(Note : for Links provided by Atlas : click)

Identity

Other namesMCF3
ROS
c-ros-1
HGNC (Hugo) ROS1
LocusID (NCBI) 6098
Atlas_Id 42144
Location 6q22.1
Location_base_pair Starts at 117609530 and ends at 117747018 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Fusion genes
(updated 2016)
ALK (2p23.2) / ROS1 (6q22.1)C10orf10 (10q11.21) / ROS1 (6q22.1)CCDC6 (10q21.2) / ROS1 (6q22.1)
CD74 (5q32) / ROS1 (6q22.1)CEP85L (6q22.31) / ROS1 (6q22.1)CLIP1 (12q24.31) / ROS1 (6q22.1)
CLTC (17q23.1) / ROS1 (6q22.1)ERC1 (12p13.33) / ROS1 (6q22.1)EZR (6q25.3) / ROS1 (6q22.1)
GOPC (6q22.1) / ROS1 (6q22.1)HLA-A (6p22.1) / ROS1 (6q22.1)KDELR2 (7p22.1) / ROS1 (6q22.1)
KMT2A (11q23.3) / ROS1 (6q22.1)LRIG3 (12q14.1) / ROS1 (6q22.1)MYO5A (15q21.2) / ROS1 (6q22.1)
PPFIBP1 (12p11.23) / ROS1 (6q22.1)PWWP2A (5q33.3) / ROS1 (6q22.1)ROS1 (6q22.1) / CCDC6 (10q21.2)
ROS1 (6q22.1) / CD74 (5q32)ROS1 (6q22.1) / EZR (6q25.3)ROS1 (6q22.1) / GOPC (6q22.1)
ROS1 (6q22.1) / LRIG3 (12q14.1)ROS1 (6q22.1) / SDC4 (20q13.12)ROS1 (6q22.1) / SLC34A2 (4p15.2)
SDC4 (20q13.12) / ROS1 (6q22.1)SHTN1 (10q25.3) / ROS1 (6q22.1)SLC34A2 (4p15.2) / ROS1 (6q22.1)
TFG (3q12.2) / ROS1 (6q22.1)TPM3 (1q21.3) / ROS1 (6q22.1)YWHAE (17p13.3) / ROS1 (6q22.1)
ZCCHC8 (12q24.31) / ROS1 (6q22.1)
Note ROS1 is proto-oncogene encoding a type I integral membrane protein with receptor tyrosine kinase (RTK) activity. ROS1 is a member of the insulin receptor family and is involved in downstream signalling processes involved in cell growth and differentiation.

DNA/RNA

Description The ROS1 gene is highly conserved from drosophila through zebrafish, rat, cow, rhesus, and homo sapiens. Refseq NM_002944.

Protein

Description ROS1 gene encodes a 2,347 amino acid protein with a molecular weight of 263,915 Daltons (NCBI: P08922). This protein is a type I single pass integral membrane protein with tyrosine kinase activity. SwissProt identifier P08922, Protein NP_002935
Expression ROS1 expression is involved in regionalization of the proximal epididymal epithelium. Expression levels have been highest in liver, platelelts, T-cells and monocytes, but is found across nearly all cell types.
Localisation ROS1 is localized to the cell plasma membrane and contains both extracellular and intracellular domains.
Function ROS1 functions as an orphan receptor tyrosine kinase with an unestablished ligand. ROS1 directly interacts via an SH2 1 domain with PTPN6 which drives ROS1 dephosphorylation (Charest et al., 2006). ROS1 has also been suggested to interact with PTPN11 leading to PI3K/mTOR signaling, and to mediate phosphorylation of VAV3 (Charest et al., 2006). The ligand for wild type ROS1 is unknown and the normal function remains unclear despite the above associations.
Homology ROS1 shares significant homology with other members of the insulin growth factor receptor family, and the gene is highly conserved back through drosophila melanogaster.

Mutations

Germinal None established.
Somatic The intrachromosomal del(6)(q21q22) deletion has been identified in glioblastoma multiforme and leads to the formation of a constitutive active GOPC-ROS1 protein (Charest et al., 2003). In non-small cell lung cancer (NSCLC) the SLC34A2-ROS1 chimeric protein also holds kinase activity. A CD74-ROS1 chimeric protein has also been identified in NSCLC (Awad et al., 2013).

Implicated in

Entity Non-small cell lung cancer, renal oncocytoma, gastric cancer, glioblastoma multiforme, cholangiocarcinoma colorectal cancer.
Note There has been a rapidly expanding appreciation of ROS1 fusion proteins in the tumorigenesis of multiple malignancies as discussed below (Charest et. al., 2003, Gu et al., 2011, Rimkunas et al., 2012, Takeuchi et al.,2012, Awad et al., 2013, Lee et al., 2013).
Disease ROS1 rearrangements occur in <2% of NSCLC and are enriched for in adenocarcinoma and young never smokers (Bergethon et al., 2012).
Prognosis To date ROS1 has not been clearly implicated as an independent prognostic variable. ROS1 rearrangements may predict sensitivity to the ALK-inhibitor Crizotinib in NSCLC. Small molecule inhibitor screens have also identified foretinib as a potent inhibitor of multiple ROS1 fusion proteins. Additionaly, ROS1 mutation has been observed as a acquired resistance mechanism to crizotinib. Davare and colleagues have shown that foretinib is capable of inhibiting the G2032R ROS1 mutant which is resistant to crizotinib (Davare et al., 2013).
Cytogenetics ROS1 rearrangements have been documented with the following fusion partners; CCDC6, CD74, CEP85L, also called C6orf204, CLTC, EZR, GOPC, KDELR2, LRIG3, SDC4, SLC34A2, and TPM3.
Translocations and fusion proteins: t(1;6)(q21;q22) TPM3/ROS1; t(4;6)(p15;q22) SLC34A2/ROS1; t(5;6)(q33;q22) CD74/ROS1; t(6;6)(q22;q22) GOPC/ROS1; t(6;6)(q22;q22) CEP85L/ROS1; t(6;6)(q22;q25) EZR/ROS1; t(6;7)(q22;p22) KDELR2/ROS1; t(6;10)(q22;q21) CCDC6/ROS1; t(6;12)(q22;q14) LRIG3/ROS1; t(6;17)(q22;q23)CLTC/ROS1; t(6;20)(q22;q12) SDC4/ROS1 (Charest et. Al., 2003, Gu et al., 2011, Rimkunas et al., 2012, Takeuchi et al., 2012, Awad et al., 2013, Lee et al., 2013, Mitelman et al., 2015). Within NSCLC ROS1 rearrangements are non-overlapping with EGFR, KRAS, and ALK genomic alterations (Davies et al., 2012, Awad et al., 2013, Go et al., 2013).
  

Breakpoints

 
Note Within the COSMIC database ROS1 chromosomal rearrangements have been documented with the following fusion partners ; CD74, EZR, GOPC, SDC4, TPM3, SLC34A2, and LRIG3 (COSMIC, accessed 12/2013).

Bibliography

Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)
Charest A, Lane K, McMahon K, Park J, Preisinger E, Conroy H, Housman D
Genes Chromosomes Cancer 2003 May;37(1):58-71
PMID 12661006
 
ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice
Charest A, Wilker EW, McLaughlin ME, Lane K, Gowda R, Coven S, McMahon K, Kovach S, Feng Y, Yaffe MB, Jacks T, Housman D
Cancer Res 2006 Aug 1;66(15):7473-81
PMID 16885344
 
Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma
Gu TL, Deng X, Huang F, Tucker M, Crosby K, Rimkunas V, Wang Y, Deng G, Zhu L, Tan Z, Hu Y, Wu C, Nardone J, MacNeill J, Ren J, Reeves C, Innocenti G, Norris B, Yuan J, Yu J, Haack H, Shen B, Peng C, Li H, Zhou X, Liu X, Rush J, Comb MJ
PLoS One 2011 Jan 6;6(1):e15640
PMID 21253578
 
Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion
Rimkunas VM, Crosby KE, Li D, Hu Y, Kelly ME, Gu TL, Mack JS, Silver MR, Zhou X, Haack H
Clin Cancer Res 2012 Aug 15;18(16):4449-57
PMID 22661537
 
Identifying and targeting ROS1 gene fusions in non-small cell lung cancer
Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, Alloisio M, Santoro A, Camidge DR, Varella-Garcia M, Doebele RC
Clin Cancer Res 2012 Sep 1;18(17):4570-9
PMID 22919003
 
Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer
Yasuda H, de Figueiredo-Pontes LL, Kobayashi S, Costa DB
J Thorac Oncol 2012 Jul;7(7):1086-90
PMID 22617245
 
RET, ROS1 and ALK fusions in lung cancer
Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y
Nat Med 2012 Feb 12;18(3):378-81
PMID 22327623
 
ROS1 rearrangements define a unique molecular class of lung cancers
Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, Massion PP, Siwak-Tapp C, Gonzalez A, Fang R, Mark EJ, Batten JM, Chen H, Wilner KD, Kwak EL, Clark JW, Carbone DP, Ji H, Engelman JA, Mino-Kenudson M, Pao W, Iafrate AJ
J Clin Oncol 2012 Mar 10;30(8):863-70
PMID 22215748
 
ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway
Ou SH, Tan J, Yen Y, Soo RA
Expert Rev Anticancer Ther 2012 Apr;12(4):447-56
PMID 22500682
 
Targeting ROS1 with anaplastic lymphoma kinase inhibitors: a promising therapeutic strategy for a newly defined molecular subset of non-small-cell lung cancer
Chin LP, Soo RA, Soong R, Ou SH
J Thorac Oncol 2012 Nov;7(11):1625-30
PMID 23070242
 
Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia
Cilloni D, Carturan S, Bracco E, Campia V, Rosso V, Torti D, Calabrese C, Gaidano V, Niparuck P, Favole A, Signorino E, Iacobucci I, Morano A, De Luca L, Musto P, Frassoni F, Saglio G
Leuk Res 2013 May;37(5):520-30
PMID 23415111
 
Acquired resistance to crizotinib from a mutation in CD74-ROS1
Awad MM, Katayama R, McTigue M, Liu W, Deng YL, Brooun A, Friboulet L, Huang D, Falk MD, Timofeevski S, Wilner KD, Lockerman EL, Khan TM, Mahmood S, Gainor JF, Digumarthy SR, Stone JR, Mino-Kenudson M, Christensen JG, Iafrate AJ, Engelman JA, Shaw AT
N Engl J Med 2013 Jun 20;368(25):2395-401
PMID 23724914
 
Clinicopathologic analysis of ROS1-rearranged non-small-cell lung cancer and proposal of a diagnostic algorithm
Go H, Kim DW, Kim D, Keam B, Kim TM, Lee SH, Heo DS, Bang YJ, Chung DH
J Thorac Oncol 2013 Nov;8(11):1445-50
PMID 24128715
 
Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins
Davare MA, Saborowski A, Eide CA, Tognon C, Smith RL, Elferich J, Agarwal A, Tyner JW, Shinde UP, Lowe SW, Druker BJ
Proc Natl Acad Sci U S A 2013 Nov 26;110(48):19519-24
PMID 24218589
 
Identification of ROS1 rearrangement in gastric adenocarcinoma
Lee J, Lee SE, Kang SY, Do IG, Lee S, Ha SY, Cho J, Kang WK, Jang J, Ou SH, Kim KM
Cancer 2013 May 1;119(9):1627-35
PMID 23400546
 
Molecular pathways: ROS1 fusion proteins in cancer
Davies KD, Doebele RC
Clin Cancer Res 2013 Aug 1;19(15):4040-5
PMID 23719267
 
Novel targets in non-small cell lung cancer: ROS1 and RET fusions
Gainor JF, Shaw AT
Oncologist 2013;18(7):865-75
PMID 23814043
 
ROS1 and ALK fusions in colorectal cancer, with evidence of intratumoral heterogeneity for molecular drivers
Aisner DL, Nguyen TT, Paskulin DD, Le AT, Haney J, Schulte N, Chionh F, Hardingham J, Mariadason J, Tebbutt N, Doebele RC, Weickhardt AJ, Varella-Garcia M
Mol Cancer Res 2014 Jan;12(1):111-8
PMID 24296758
 
Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer
Mitelman F Johansson B and Mertens F
http://cgap.nci.nih.gov/Chromosomes/Mitelman
 
Efficacy and safety of crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC).
Ou S, Bang Y, Camidge D, et al.
ASCO Meeting Abstracts 2013;31:8032
 

Citation

This paper should be referenced as such :
Klempner SJ, Ou SH
ROS1 (ROS proto-oncogene 1 , receptor tyrosine kinase);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/ROS1ID42144ch6q22.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Lung: Adenocarcinoma with t(6;12)(q22;q14.1) LRIG3/ROS1
Lung: Translocations in Adenocarcinoma
Lung: Translocations in Squamous Cell Carcinoma

External links

Nomenclature
HGNC (Hugo)ROS1   10261
Cards
AtlasROS1ID42144ch6q22
Entrez_Gene (NCBI)ROS1  6098  ROS proto-oncogene 1, receptor tyrosine kinase
GeneCards (Weizmann)ROS1
Ensembl hg19 (Hinxton)ENSG00000047936 [Gene_View]  chr6:117609530-117747018 [Contig_View]  ROS1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000047936 [Gene_View]  chr6:117609530-117747018 [Contig_View]  ROS1 [Vega]
ICGC DataPortalENSG00000047936
TCGA cBioPortalROS1
AceView (NCBI)ROS1
Genatlas (Paris)ROS1
WikiGenes6098
SOURCE (Princeton)ROS1
Genomic and cartography
GoldenPath hg19 (UCSC)ROS1  -     chr6:117609530-117747018 -  6q21-q22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ROS1  -     6q21-q22   [Description]    (hg38-Dec_2013)
EnsemblROS1 - 6q21-q22 [CytoView hg19]  ROS1 - 6q21-q22 [CytoView hg38]
Mapping of homologs : NCBIROS1 [Mapview hg19]  ROS1 [Mapview hg38]
OMIM165020   
Gene and transcription
Genbank (Entrez)BC144556 BC166687 M13880 M34353
RefSeq transcript (Entrez)NM_002944
RefSeq genomic (Entrez)NC_000006 NC_018917 NG_033929 NT_025741 NW_004929328
Consensus coding sequences : CCDS (NCBI)ROS1
Cluster EST : UnigeneHs.1041 [ NCBI ]
CGAP (NCI)Hs.1041
Alternative Splicing GalleryENSG00000047936
Gene ExpressionROS1 [ NCBI-GEO ]   ROS1 [ EBI - ARRAY_EXPRESS ]   ROS1 [ SEEK ]   ROS1 [ MEM ]
Gene Expression Viewer (FireBrowse)ROS1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6098
GTEX Portal (Tissue expression)ROS1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP08922 (Uniprot)
NextProtP08922  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP08922
Splice isoforms : SwissVarP08922 (Swissvar)
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
PhosPhoSitePlusP08922
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    RECEPTOR_TYR_KIN_II (PS00239)   
Domains : Interpro (EBI)6-blade_b-propeller_TolB-like    FN3_dom    Ig-like_fold    Kinase-like_dom    LDLR_classB_rpt    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom    Tyr_kinase_rcpt_2_CS   
Domain families : Pfam (Sanger)fn3 (PF00041)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam00041    pfam07714   
Domain families : Smart (EMBL)FN3 (SM00060)  LY (SM00135)  TyrKc (SM00219)  
DMDM Disease mutations6098
Blocks (Seattle)ROS1
PDB (SRS)3ZBF    4UXL   
PDB (PDBSum)3ZBF    4UXL   
PDB (IMB)3ZBF    4UXL   
PDB (RSDB)3ZBF    4UXL   
Structural Biology KnowledgeBase3ZBF    4UXL   
SCOP (Structural Classification of Proteins)3ZBF    4UXL   
CATH (Classification of proteins structures)3ZBF    4UXL   
SuperfamilyP08922
Human Protein AtlasENSG00000047936
Peptide AtlasP08922
HPRD01295
IPIIPI00288965   IPI00647703   IPI00647258   
Protein Interaction databases
DIP (DOE-UCLA)P08922
IntAct (EBI)P08922
FunCoupENSG00000047936
BioGRIDROS1
STRING (EMBL)ROS1
ZODIACROS1
Ontologies - Pathways
QuickGOP08922
Ontology : AmiGOcolumnar/cuboidal epithelial cell development  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  plasma membrane  protein phosphorylation  transmembrane receptor protein tyrosine kinase signaling pathway  spermatogenesis  cell proliferation  cell surface  negative regulation of gene expression  regulation of phosphate transport  membrane  integral component of membrane  cell growth  protein phosphatase binding  signal transduction by protein phosphorylation  cell differentiation  regulation of TOR signaling  peptidyl-tyrosine autophosphorylation  perinuclear region of cytoplasm  regulation of ERK1 and ERK2 cascade  
Ontology : EGO-EBIcolumnar/cuboidal epithelial cell development  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  plasma membrane  protein phosphorylation  transmembrane receptor protein tyrosine kinase signaling pathway  spermatogenesis  cell proliferation  cell surface  negative regulation of gene expression  regulation of phosphate transport  membrane  integral component of membrane  cell growth  protein phosphatase binding  signal transduction by protein phosphorylation  cell differentiation  regulation of TOR signaling  peptidyl-tyrosine autophosphorylation  perinuclear region of cytoplasm  regulation of ERK1 and ERK2 cascade  
NDEx Network
Atlas of Cancer Signalling NetworkROS1
Wikipedia pathwaysROS1
Orthology - Evolution
OrthoDB6098
GeneTree (enSembl)ENSG00000047936
Phylogenetic Trees/Animal Genes : TreeFamROS1
Homologs : HomoloGeneROS1
Homology/Alignments : Family Browser (UCSC)ROS1
Gene fusions - Rearrangements
Fusion : MitelmanCCDC6/ROS1 [10q21.2/6q22.1]  [t(6;10)(q22;q21)]  
Fusion : MitelmanCD74/ROS1 [5q32/6q22.1]  [t(5;6)(q33;q22)]  
Fusion : MitelmanCEP85L/ROS1 [6q22.31/6q22.1]  [t(6;6)(q22;q22)]  
Fusion : MitelmanCLTC/ROS1 [17q23.1/6q22.1]  [t(6;17)(q22;q23)]  
Fusion : MitelmanEZR/ROS1 [6q25.3/6q22.1]  [inv(6)(q22q25)]  [t(6;6)(q22;q25)]  
Fusion : MitelmanGOPC/ROS1 [6q22.1/6q22.1]  [del(6)(q22)]  [del(6)(q22q22)]  
[t(6;6)(q22;q22)]  
Fusion : MitelmanKDELR2/ROS1 [7p22.1/6q22.1]  [t(6;7)(q22;p22)]  
Fusion : MitelmanKMT2A/ROS1 [11q23.3/6q22.1]  [t(6;6)(q22;q22)]  
Fusion : MitelmanLRIG3/ROS1 [12q14.1/6q22.1]  [t(6;12)(q22;q14)]  
Fusion : MitelmanROS1/CD74 [6q22.1/5q32]  [t(5;6)(q33;q22)]  
Fusion : MitelmanSDC4/ROS1 [20q13.12/6q22.1]  [t(6;20)(q22;q12)]  
Fusion : MitelmanSLC34A2/ROS1 [4p15.2/6q22.1]  [t(4;6)(p15;q22)]  
Fusion : MitelmanTFG/ROS1 [3q12.2/6q22.1]  [t(3;6)(q12;q22)]  
Fusion : MitelmanTPM3/ROS1 [1q21.3/6q22.1]  [t(1;6)(q21;q22)]  
Fusion : MitelmanYWHAE/ROS1 [17p13.3/6q22.1]  [t(6;17)(q22;p13)]  
Fusion : COSMICZCCHC8 [12q24.31]  -  ROS1 [6q22.1]  [fusion_1645]  [fusion_1646]  
Fusion: TCGAC6orf204 ROS1 6q22.1 GBM
Fusion: TCGACLTC 17q23.1 ROS1 6q22.1 LUAD
Fusion: TCGAEZR 6q25.3 ROS1 6q22.1 LUAD
Fusion : TICdbCD74 [5q32]  -  ROS1 [6q22.1]
Fusion : TICdbGOPC [6q22.1]  -  ROS1 [6q22.1]
Fusion : TICdbSLC34A2 [4p15.2]  -  ROS1 [6q22.1]
Fusion Cancer (Beijing)CCDC6 [10q21.2]  -  ROS1 [6q22.1]  [FUSC002622]  [FUSC002622]
Fusion Cancer (Beijing)CD74 [5q32]  -  ROS1 [6q22.1]  [FUSC003425]  [FUSC003425]
Fusion Cancer (Beijing)ROS1 [6q22.1]  -  CCDC6 [10q21.2]  [FUSC002665]  [FUSC002665]
Fusion Cancer (Beijing)SLC34A2 [4p15.2]  -  ROS1 [6q22.1]  [FUSC003670]  [FUSC003670]
Polymorphisms : SNP, variants
NCBI Variation ViewerROS1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ROS1
dbVarROS1
ClinVarROS1
1000_GenomesROS1 
Exome Variant ServerROS1
ExAC (Exome Aggregation Consortium)ROS1 (select the gene name)
Genetic variants : HAPMAP6098
Genomic Variants (DGV)ROS1 [DGVbeta]
Mutations
ICGC Data PortalROS1 
TCGA Data PortalROS1 
Broad Tumor PortalROS1
OASIS PortalROS1 [ Somatic mutations - Copy number]
Cancer Gene: CensusROS1 
Somatic Mutations in Cancer : COSMICROS1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ROS1
DgiDB (Drug Gene Interaction Database)ROS1
DoCM (Curated mutations)ROS1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ROS1 (select a term)
intoGenROS1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)6:117609530-117747018  ENSG00000047936
CONAN: Copy Number AnalysisROS1 
Mutations and Diseases : HGMDROS1
OMIM165020   
MedgenROS1
Genetic Testing Registry ROS1
NextProtP08922 [Medical]
TSGene6098
GENETestsROS1
Huge Navigator ROS1 [HugePedia]
snp3D : Map Gene to Disease6098
BioCentury BCIQROS1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6098
Chemical/Pharm GKB GenePA34633
Clinical trialROS1
Miscellaneous
canSAR (ICR)ROS1 (select the gene name)
Probes
Litterature
PubMed87 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineROS1
EVEXROS1
GoPubMedROS1
iHOPROS1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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