Fusion genes
(updated 2016) | ALK (2p23.2) / NPM1 (5q35.1) | BSPRY (9q32) / NPM1 (5q35.1) | FBXW11 (5q35.1) / NPM1 (5q35.1) |
| |
FERMT2 (14q22.1) / NPM1 (5q35.1) | INPPL1 (11q13.4) / NPM1 (5q35.1) | MLF1 (3q25.32) / NPM1 (5q35.1) |
| |
NPM1 (5q35.1) / ALK (2p23.2) | NPM1 (5q35.1) / MLF1 (3q25.32) | NPM1 (5q35.1) / NCL (2q37.1) |
| |
NPM1 (5q35.1) / PTMA (2q37.1) | NPM1 (5q35.1) / RAB40B (17q25.3) | NPM1 (5q35.1) / RAB4A (1q42.13) |
| |
NPM1 (5q35.1) / RARA (17q21.2) | NPM1 (5q35.1) / TYK2 (19p13.2) | RAB40B (17q25.3) / NPM1 (5q35.1) |
| |
RARA (17q21.2) / NPM1 (5q35.1) | TXNRD1 (12q23.3) / NPM1 (5q35.1) |
| Note | |
| Entity | Anaplasic large cell lymphoma (ALCL) with t(2;5)(p23;q35) --> NPM1-ALK |
| Disease | ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); 80% of ALK+ ALCL cases bear a t(2;5) |
| Prognosis | nonetheless, a 80% five yr survival may be associated with this anomaly |
| Cytogenetics | additional anomalies are most often found |
| Hybrid/Mutated Gene | 5' NPM1-3' ALK on der(5) |
| Abnormal Protein | 680 amino acids, 80 kDa; N-term 116 amino acids from NPM1 fused to the 563 C-term aminoacids of ALK (i.e. composed of the oligomerization domain and the metal binding site of NPM1 ,and the entire cytoplasmic portion of ALK); no apparent expression of the ALK/NPM1 counterpart; Characteristic localisation both in the cytoplasm and in the nucleus, due to heterooligomerization of NPM-ALK and normal NPM whereas the normal NPM protein is confined to the nucleus; constitutive activation of the catalytic domain of ALK. |
| Oncogenesis | via the kinase function activated by oligomerization of NPM1-ALK mediated by the NPM1 part |
| | |
| Entity | t(3;5)(q25;q34)/in myeloid malignancies --> NPM - MLF1 |
| Disease | Acute non lymphocytic leukemia (AML), myelodysplasia (MDS), chronic myelogenous leukemia in blast crisis (BC-CML); trilineage involvement |
| Prognosis | very poor |
| Cytogenetics | location of breakpoints difficult to ascertain |
| Hybrid/Mutated Gene | 5' NPM-3' MLF1 on der(5) |
| Abnormal Protein | with the 175 N term amino acids of NPM1; nuclear protein |
| | |
| Entity | t(5;17)(q34;q21)/M3-AML --> NPM1-RARa |
| Disease | promyelocytic AML (M3-AML) |
| Cytogenetics | variant translocation of the well known t(15;17) |
| Hybrid/Mutated Gene | 5' NPM1-3' RARa on der(5) |
| Abnormal Protein | with the 117 N term amino acids of NPM1 |
| | |
| Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. |
| Bischof D, Pulford K, Mason DY, Morris SW |
| Molecular and cellular biology. 1997 ; 17 (4) : 2312-2325. |
| PMID 9121481 |
| |
| Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region. |
| Chan PK, Chan FY, Morris SW, Xie Z |
| Nucleic acids research. 1997 ; 25 (6) : 1225-1232. |
| PMID 9092633 |
| |
| Anaplastic large cell lymphomas, Primary systemic (T/Null cell type). |
| Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe E |
| World Health Organization (WHO) Classification of Tumors.. |
| |
| Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. |
| Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (9) : 1533-1559. |
| PMID 10994999 |
| |
| Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. |
| Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT |
| Science (New York, N.Y.). 1994 ; 263 (5151) : 1281-1284. |
| PMID 8122112 |
| |
| Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. |
| Morris SW, Xue L, Ma Z, Kinney MC |
| British journal of haematology. 2001 ; 113 (2) : 275-295. |
| PMID 11380391 |
| |
| The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. |
| Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ |
| Blood. 1996 ; 87 (3) : 882-886. |
| PMID 8562957 |
| |
| CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. |
| Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B |
| Blood. 2000 ; 96 (12) : 3681-3695. |
| PMID 11090048 |
| |
| The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. |
| Yoneda-Kato N, Look AT, Kirstein MN, Valentine MB, Raimondi SC, Cohen KJ, Carroll AJ, Morris SW |
| Oncogene. 1996 ; 12 (2) : 265-275. |
| PMID 8570204 |
| |
| Nomenclature |
|---|
| HGNC (Hugo) | NPM1 7910 |
| Cards |
|---|
| Atlas | NPM1ID22 |
| Entrez_Gene (NCBI) | NPM1 4869 nucleophosmin (nucleolar phosphoprotein B23, numatrin) |
| Aliases | B23; NPM |
| GeneCards (Weizmann) | NPM1 |
| Ensembl hg19 (Hinxton) | ENSG00000181163 [Gene_View] chr5:170814708-170833731 [Contig_View] NPM1 [Vega] |
| Ensembl hg38 (Hinxton) | ENSG00000181163 [Gene_View] chr5:170814708-170833731 [Contig_View] NPM1 [Vega] |
| ICGC DataPortal | ENSG00000181163 |
| TCGA cBioPortal | NPM1 |
| AceView (NCBI) | NPM1 |
| Genatlas (Paris) | NPM1 |
| WikiGenes | 4869 |
| SOURCE (Princeton) | NPM1 |
| Genomic and cartography |
|---|
| GoldenPath hg19 (UCSC) | NPM1 - chr5:170814708-170833731 + 5q35.1 [Description] (hg19-Feb_2009) |
| GoldenPath hg38 (UCSC) | NPM1 - 5q35.1 [Description] (hg38-Dec_2013) |
| Ensembl | NPM1 - 5q35.1 [CytoView hg19] NPM1 - 5q35.1 [CytoView hg38] |
| Mapping of homologs : NCBI | NPM1 [Mapview hg19] NPM1 [Mapview hg38] |
| OMIM | 164040 |
| Gene and transcription |
|---|
| Genbank (Entrez) | AB042278 AB451236 AB451361 AI687394 AK000472 |
| RefSeq transcript (Entrez) | NM_001037738 NM_002520 NM_199185 |
| RefSeq genomic (Entrez) | NC_000005 NC_018916 NG_016018 NT_023133 NW_004929325 |
| Consensus coding sequences : CCDS (NCBI) | NPM1 |
| Cluster EST : Unigene | Hs.557550 [ NCBI ] |
| CGAP (NCI) | Hs.557550 |
| Alternative Splicing Gallery | ENSG00000181163 |
| Gene Expression | NPM1 [ NCBI-GEO ] NPM1 [ EBI - ARRAY_EXPRESS ]
NPM1 [ SEEK ] NPM1 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | NPM1 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevisible | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 4869 |
| GTEX Portal (Tissue expression) | NPM1 |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | P06748 (Uniprot) |
| NextProt | P06748 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | P06748 |
| Splice isoforms : SwissVar | P06748 (Swissvar) |
| PhosPhoSitePlus | P06748 |
| Domains : Interpro (EBI) | NPM1_C Nucleoplasmin Nucleoplasmin_core_dom |
| Domain families : Pfam (Sanger) | NPM1-C (PF16276) |
| Domain families : Pfam (NCBI) | pfam16276 |
| DMDM Disease mutations | 4869 |
| Blocks (Seattle) | NPM1 |
| PDB (SRS) | 2LLH 2P1B 2VXD |
| PDB (PDBSum) | 2LLH 2P1B 2VXD |
| PDB (IMB) | 2LLH 2P1B 2VXD |
| PDB (RSDB) | 2LLH 2P1B 2VXD |
| Structural Biology KnowledgeBase | 2LLH 2P1B 2VXD |
| SCOP (Structural Classification of Proteins) | 2LLH 2P1B 2VXD |
| CATH (Classification of proteins structures) | 2LLH 2P1B 2VXD |
| Superfamily | P06748 |
| Human Protein Atlas | ENSG00000181163 |
| Peptide Atlas | P06748 |
| HPRD | 01246 |
| IPI | IPI00549248 IPI00220740 IPI00604504 IPI00658013 IPI00985410 IPI00983818 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | P06748 |
| IntAct (EBI) | P06748 |
| FunCoup | ENSG00000181163 |
| BioGRID | NPM1 |
| STRING (EMBL) | NPM1 |
| ZODIAC | NPM1 |
| Ontologies - Pathways |
|---|
| QuickGO | P06748 |
| Ontology : AmiGO | transcription coactivator activity RNA binding protein kinase inhibitor activity protein binding nucleus nucleus nucleoplasm nucleoplasm nucleolus cytoplasm cytoplasm centrosome centrosome cytosol focal adhesion DNA repair nucleosome assembly intracellular protein transport nucleocytoplasmic transport nucleocytoplasmic transport response to stress DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest centrosome cycle centrosome cycle signal transduction cell aging cell aging protein localization positive regulation of cell proliferation negative regulation of cell proliferation negative regulation of cell proliferation negative regulation of centrosome duplication membrane viral process protein kinase binding intracellular ribonucleoprotein complex Tat protein binding spindle pole centrosome regulation of endodeoxyribonuclease activity CENP-A containing nucleosome assembly ribosome assembly histone binding protein homodimerization activity ribosomal large subunit binding ribosomal small subunit binding negative regulation of apoptotic process negative regulation of apoptotic process negative regulation of protein kinase activity by regulation of protein phosphorylation poly(A) RNA binding positive regulation of translation positive regulation of transcription, DNA-templated regulation of centriole replication protein heterodimerization activity NF-kappaB binding NF-kappaB binding unfolded protein binding unfolded protein binding positive regulation of NF-kappaB transcription factor activity protein oligomerization regulation of endoribonuclease activity regulation of eIF2 alpha phosphorylation by dsRNA positive regulation of cell cycle G2/M phase transition |
| Ontology : EGO-EBI | transcription coactivator activity RNA binding protein kinase inhibitor activity protein binding nucleus nucleus nucleoplasm nucleoplasm nucleolus cytoplasm cytoplasm centrosome centrosome cytosol focal adhesion DNA repair nucleosome assembly intracellular protein transport nucleocytoplasmic transport nucleocytoplasmic transport response to stress DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest centrosome cycle centrosome cycle signal transduction cell aging cell aging protein localization positive regulation of cell proliferation negative regulation of cell proliferation negative regulation of cell proliferation negative regulation of centrosome duplication membrane viral process protein kinase binding intracellular ribonucleoprotein complex Tat protein binding spindle pole centrosome regulation of endodeoxyribonuclease activity CENP-A containing nucleosome assembly ribosome assembly histone binding protein homodimerization activity ribosomal large subunit binding ribosomal small subunit binding negative regulation of apoptotic process negative regulation of apoptotic process negative regulation of protein kinase activity by regulation of protein phosphorylation poly(A) RNA binding positive regulation of translation positive regulation of transcription, DNA-templated regulation of centriole replication protein heterodimerization activity NF-kappaB binding NF-kappaB binding unfolded protein binding unfolded protein binding positive regulation of NF-kappaB transcription factor activity protein oligomerization regulation of endoribonuclease activity regulation of eIF2 alpha phosphorylation by dsRNA positive regulation of cell cycle G2/M phase transition |
| REACTOME | P06748 [protein] |
| REACTOME Pathways | R-HSA-180746 Nuclear import of Rev protein [pathway] |
| REACTOME Pathways | R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere [pathway] |
| NDEx Network | NPM1 |
| Atlas of Cancer Signalling Network | NPM1 |
| Wikipedia pathways | NPM1 |
| Orthology - Evolution |
|---|
| OrthoDB | 4869 |
| GeneTree (enSembl) | ENSG00000181163 |
| Phylogenetic Trees/Animal Genes : TreeFam | NPM1 |
| Homologs : HomoloGene | NPM1 |
| Homology/Alignments : Family Browser (UCSC) | NPM1 |
| Gene fusions - Rearrangements |
|---|
| Fusion : Mitelman | BSPRY/NPM1 [9q32/5q35.1] [t(5;9)(q35;q32)] |
| Fusion : Mitelman | NPM1/ALK [5q35.1/2p23.2] [ins(5;2)(q35;p23p23)] [t(2;5)(p23;q35)] |
| |
| Fusion : Mitelman | NPM1/MLF1 [5q35.1/3q25.32] [ins(3;5)(q25;q31q35)] [t(3;5)(q25;q35)] |
| |
| Fusion : Mitelman | NPM1/RAB4A [5q35.1/1q42.13] [t(1;5)(q42;q35)] |
| Fusion : Mitelman | NPM1/RARA [5q35.1/17q21.2] [t(11;17)(q23;q21)] [t(15;17)(q22;q21)] |
| [t(5;17)(q35;q21)] |
| Fusion : Mitelman | NPM1/TYK2 [5q35.1/19p13.2] [t(5;19)(q35;p13)] |
| Fusion : COSMIC | NPM1 [5q35.1] - ALK [2p23.2] [fusion_198] [fusion_199] [fusion_200] [fusion_201] [fusion_420] [fusion_448] [fusion_449] |
| [fusion_450] [fusion_451] [fusion_452] [fusion_453] [fusion_454] [fusion_455] [fusion_456] [fusion_457] [fusion_458] |
| Fusion: TCGA | BSPRY 9q32 NPM1 5q35.1 BRCA |
| Fusion: TCGA | NPM1 5q35.1 RAB4A 1q42.13 BRCA |
| Fusion : TICdb | NPM1 [5q35.1] - ALK [2p23.2] |
| Fusion : TICdb | NPM1 [5q35.1] - MLF1 [3q25.32] |
| Fusion : TICdb | NPM1 [5q35.1] - RARA [17q21.2] |
| Polymorphisms : SNP, variants |
|---|
| NCBI Variation Viewer | NPM1 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | NPM1 |
| dbVar | NPM1 |
| ClinVar | NPM1 |
| 1000_Genomes | NPM1 |
| Exome Variant Server | NPM1 |
| ExAC (Exome Aggregation Consortium) | NPM1 (select the gene name) |
| Genetic variants : HAPMAP | 4869 |
| Genomic Variants (DGV) | NPM1 [DGVbeta] |
| Mutations |
|---|
| ICGC Data Portal | NPM1 |
| TCGA Data Portal | NPM1 |
| Broad Tumor Portal | NPM1 |
| OASIS Portal | NPM1 [ Somatic mutations - Copy number] |
| Cancer Gene: Census | NPM1 |
| Somatic Mutations in Cancer : COSMIC | NPM1 |
| intOGen Portal | NPM1 |
| 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 |
| BioMuta | search NPM1 |
| DgiDB (Drug Gene Interaction Database) | NPM1 |
| DoCM (Curated mutations) | NPM1 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | NPM1 (select a term) |
| intoGen | NPM1 |
| Impact of mutations | [PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] |
| Diseases |
|---|
| DECIPHER (Syndromes) | 5:170814708-170833731 ENSG00000181163 |
| CONAN: Copy Number Analysis | NPM1 |
| Mutations and Diseases : HGMD | NPM1 |
| OMIM | 164040 |
| Medgen | NPM1 |
| Genetic Testing Registry | NPM1
|
| NextProt | P06748 [Medical] |
| TSGene | 4869 |
| GENETests | NPM1 |
| Huge Navigator |
NPM1 [HugePedia] |
| snp3D : Map Gene to Disease | 4869 |
| BioCentury BCIQ | NPM1 |
| ClinGen | NPM1 |
| Clinical trials, drugs, therapy |
|---|
| Chemical/Protein Interactions : CTD | 4869 |
| Chemical/Pharm GKB Gene | PA31712 |
| Clinical trial | NPM1 |
| Miscellaneous |
|---|
| canSAR (ICR) | NPM1 (select the gene name) |
| Other database | http://cancergenome.broadinstitute.org/index.php?tgene=NPM1 |
| Probes |
|---|
| Litterature |
|---|
| PubMed | 499 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | NPM1 |
| EVEX | NPM1 |
| GoPubMed | NPM1 |
| iHOP | NPM1 |
