NPM1 (nucleophosmin)

2001-08-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
5q35.1
IMAGE
Atlas Image
LEGEND
NPM1 (5q35) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
B23,NPM
FUSION GENES

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

Proteins

Atlas Image
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

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 gene
5 NPM1-3 ALK on der(5)
Fusion 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 name
t(3;5)(q25;q34)/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 gene
5 NPM-3 MLF1 on der(5)
Fusion protein
with the 175 N term amino acids of NPM1; nuclear protein
Entity name
Disease
promyelocytic AML (M3-AML)
Cytogenetics
variant translocation of the well known t(15;17)
Hybrid gene
5 NPM1-3 RARa on der(5)
Fusion protein
with the 117 N term amino acids of NPM1

Breakpoints

Atlas Image
Atlas Image

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

Pubmed IDLast YearTitleAuthors
91214811997Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.Bischof D et al
90926331997Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region.Chan PK et al
109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
81221121994Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.Morris SW et al
113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
85629571996The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.Redner RL et al
110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al
85702041996The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.Yoneda-Kato N et al

Other Information

Locus ID:

NCBI: 4869
MIM: 164040
HGNC: 7910
Ensembl: ENSG00000181163

Variants:

dbSNP: 4869
ClinVar: 4869
TCGA: ENSG00000181163
COSMIC: NPM1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000181163ENST00000296930P06748
ENSG00000181163ENST00000296930A0A0S2Z491
ENSG00000181163ENST00000351986P06748
ENSG00000181163ENST00000351986A0A0S2Z4G7
ENSG00000181163ENST00000393820P06748
ENSG00000181163ENST00000393820A0A140VJQ2
ENSG00000181163ENST00000517671P06748
ENSG00000181163ENST00000517671A0A0S2Z491
ENSG00000181163ENST00000521672E5RI98
ENSG00000181163ENST00000523622E5RGW4

Expression (GTEx)

0
500
1000
1500
2000

Pathways

PathwaySourceExternal ID
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
HIV InfectionREACTOMER-HSA-162906
Host Interactions of HIV factorsREACTOMER-HSA-162909
Interactions of Rev with host cellular proteinsREACTOMER-HSA-177243
Nuclear import of Rev proteinREACTOMER-HSA-180746
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Cell CycleREACTOMER-HSA-1640170
Chromosome MaintenanceREACTOMER-HSA-73886
Nucleosome assemblyREACTOMER-HSA-774815
Deposition of new CENPA-containing nucleosomes at the centromereREACTOMER-HSA-606279
TP53 Regulates Transcription of Cell Cycle GenesREACTOMER-HSA-6791312
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertainREACTOMER-HSA-6804115
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factorsREACTOMER-HSA-8864260
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiationREACTOMER-HSA-8869496

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA166153473venetoclaxChemicalLabelAnnotationassociated
PA166169917midostaurinChemicalLabelAnnotationassociated

References

Pubmed IDYearTitleCitations
156597252005Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.411
183089312008Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin.186
146365742003Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation.170
179570272008The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia.163
179570272008The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia.163
120803482002Nucleophosmin regulates the stability and transcriptional activity of p53.152
267897272016Assessment of Minimal Residual Disease in Standard-Risk AML.152
164559562006Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML).150
164559562006Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML).150
160768672005Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype.143

Citation

Jean-Loup Huret

NPM1 (nucleophosmin)

Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

Online version: http://atlasgeneticsoncology.org/gene/22/npm1

Historical Card

1997-12-01 NPM1 (nucleophosmin) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France