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NPM1 (nucleophosmin)

Written2001-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
This article is an update of :
1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)NPM
B23
Numatrin
NO38
HGNC (Hugo) NPM1
HGNC Alias symbB23
NPM
HGNC Alias namenucleolar phosphoprotein B23
 numatrin
 nucleophosmin/nucleoplasmin family, member 1
HGNC Previous namenucleophosmin (nucleolar phosphoprotein B23, numatrin)
 nucleophosmin
LocusID (NCBI) 4869
Atlas_Id 22
Location 5q35.1  [Link to chromosome band 5q35]
Location_base_pair Starts at 171387704 and ends at 171410884 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping NPM1.png]
 
  NPM1 (5q35) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ALK (2p23.2)::NPM1 (5q35.1)BSPRY (9q32)::NPM1 (5q35.1)FBXW11 (5q35.1)::NPM1 (5q35.1)
FERMT2 (14q22.1)::NPM1 (5q35.1)FGFR2 (10q26.13)::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)

DNA/RNA

Description 11 exons on 25 kb;
Transcription in a centromeric --> telomeric orientation; transcription is cell-cycle regulated, reaching peaks at G1/S transition and being baseline at S/G2 1.6 kb mRNA

Protein

 
  DNA Diagram
Description 294 amino acids, 32.5 kDa; contains in C-term an oligomerization domain (residues 1-83), a metal binding site (residues 104-115) , 2 domains rich in acidic amino acids (residues 120- 132 and 161-188) , and 2 nuclear localisation signals in C-term; forms homo-hexameres; binds to single and double strand nucleic acids
Expression wide
Localisation nuclear, mainly in the nucleolus
Function RNA binding nucleolar phosphoprotein involved in preribosomal assembly; transport ribonucleoproteins between cellular compartments
Homology with nucleoplasmin

Implicated in

Note
  
Entity Anaplasic large cell lymphoma (ALCL) with --> 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 /in myeloid malignancies --> NPM1 - 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 /M3-AML --> NPM1-RARa
Disease promyelocytic AML (M3-AML)
Cytogenetics variant translocation of the well known
Hybrid/Mutated Gene 5' NPM1-3' RARa on der(5)
Abnormal Protein with the 117 N term amino acids of NPM1
  

Breakpoints

 
 
Note within the 4th intron in the cases of t(2;5) or t(5;17), within the 6th intron in case of t(3;5)

Bibliography

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
 

Citation

This paper should be referenced as such :
Huret, JL
NPM1 (nucleophosmin)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):265-267.
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Huret, JL. NPM1 (nucleophosmin). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):70-71.
http://documents.irevues.inist.fr/bitstream/handle/2042/32058/12-1997-NPM1ID22.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 34 ]
  Acute myeloid leukemia with myelodysplasia related changes
Anaplastic large cell lymphoma (ALCL)
Classification of myelodysplasic syndromes 1999
Chronic Myelomonocytic Leukemia (CMML)
i(17q) solely in myeloid malignancies
i(4p) in myeloid malignancies
inv(2)(p23q35) ATIC::ALK
inv(3)(q21q26) RPN1::MECOM::t(3;3)(q21;q26) RPN1/MECOM::ins(3;3)(q26;q21q26) RPN1/MECOM
M3::M3v acute myeloid leukemia (AML M3::M3v)
::Acute promyelocytic leukemia (APL)
::Acute promyelocytic leukemia (APL) PML::RARA

Mixed phenotype acute leukemia (MPAL)
Myeloid sarcoma
Primary mediastinal B-cell lymphoma (PMBL)
t(1;2)(q25;p23) TPM3::ALK
t(2;2)(p22;p22) LTBP1::BIRC6::del(2)(p22p22) LTBP1::BIRC6
t(2;3)(p23;q21) TFG::ALK
t(2;5)(p23;q35) NPM1::ALK
t(2;5)(p23;q35) SQSTM1::ALK
t(2;11)(p23;q12.3) EEF1G::ALK
t(2;17)(p23;q23) CLTC::ALK
t(2;17)(p23;q25) RNF213::ALK
t(2;22)(p23;q11) CLTCL1::ALK
t(2;22)(p23;q11) MYH9::ALK
t(3;5)(q25;q34) NPM1::MLF1
t(3;21)(q26;q22) RUNX1::MECOM
t(4;17)(q12;q21) FIP1L1::RARA
t(5;17)(q35;q21) without RARA involvement in non-M3 AML
t(X;2)(q11;p23) MSN::ALK
t(11;17)(q23;q21) ZBTB16::RARA
t(11;17)(q13;q21) NUMA1::RARA
t(15;17)(q24;q21) PML::RARA
t(5;17)(q35;q21) NPM1::RARA
Classification of T-Cell disorders
Therapy-Related Hematopoietic Neoplasia
t(5;19)(q35;p13) NPM1::TYK2


External links

Nomenclature
HGNC (Hugo)NPM1   7910
LRG (Locus Reference Genomic)LRG_458
Cards
AtlasNPM1ID22
Entrez_Gene (NCBI)NPM1    nucleophosmin 1
AliasesB23; NPM
GeneCards (Weizmann)NPM1
Ensembl hg19 (Hinxton)ENSG00000181163 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000181163 [Gene_View]  ENSG00000181163 [Sequence]  chr5:171387704-171410884 [Contig_View]  NPM1 [Vega]
ICGC DataPortalENSG00000181163
TCGA cBioPortalNPM1
AceView (NCBI)NPM1
Genatlas (Paris)NPM1
SOURCE (Princeton)NPM1
Genetics Home Reference (NIH)NPM1
Genomic and cartography
GoldenPath hg38 (UCSC)NPM1  -     chr5:171387704-171410884 +  5q35.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NPM1  -     5q35.1   [Description]    (hg19-Feb_2009)
GoldenPathNPM1 - 5q35.1 [CytoView hg19]  NPM1 - 5q35.1 [CytoView hg38]
ImmunoBaseENSG00000181163
Genome Data Viewer NCBINPM1 [Mapview hg19]  
OMIM164040   601626   
Gene and transcription
Genbank (Entrez)AB042278 AB451236 AB451361 AI687394 AK000472
RefSeq transcript (Entrez)NM_001037738 NM_001355006 NM_001355007 NM_001355009 NM_001355010 NM_002520 NM_199185
Consensus coding sequences : CCDS (NCBI)NPM1
Gene ExpressionNPM1 [ NCBI-GEO ]   NPM1 [ EBI - ARRAY_EXPRESS ]   NPM1 [ SEEK ]   NPM1 [ MEM ]
Gene Expression Viewer (FireBrowse)NPM1 [ Firebrowse - Broad ]
GenevisibleExpression of NPM1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4869
GTEX Portal (Tissue expression)NPM1
Human Protein AtlasENSG00000181163-NPM1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)NPM1
Human Protein Atlas [tissue]ENSG00000181163-NPM1 [tissue]
HPRD01246
Protein Interaction databases
BioGRIDNPM1
STRING (EMBL)NPM1
ZODIACNPM1
Ontologies - Pathways
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXNPM1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:23:53 CEST 2021

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jlhuret@AtlasGeneticsOncology.org.