NPM1 Gene: Nucleophosmin 1 - Role in Cancer and Ribosome Biogenesis
A comprehensive guide to the NPM1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | NPM1 |
|---|---|
| Full Name | Nucleophosmin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.1 |
| NCBI Gene ID | 4869 ncbi.nlm.nih.gov/gene/4869 |
| Ensembl ID | ENSG00000181163 |
| UniProt ID | P06748 |
| OMIM ID | 164040 |
| HGNC ID | 7910 |
| Aliases | B23, NPM, nucleolar phosphoprotein B23, numatrin |
Description
The NPM1 gene encodes nucleophosmin, a multifunctional nucleolar phosphoprotein involved in ribosome biogenesis, centrosome duplication, histone assembly, and regulation of the ARF-p53 tumor suppressor pathway. It shuttles between the nucleus and cytoplasm, playing roles in cell growth, proliferation, and stress responses. NPM1 is frequently mutated in acute myeloid leukemia (AML), where mutations lead to aberrant cytoplasmic localization of the protein, contributing to leukemogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | NPM1 mutations (type A, B, C, etc.) create a nuclear export signal (NES) at the C-terminus, causing cytoplasmic mislocalization of NPM1. This disrupts its tumor suppressor functions and alters gene expression, contributing to leukemogenesis. | Somatic mutations in NPM1 are found in ~30% of adult AML cases (COSMIC, ClinVar). |
| Myelodysplastic Syndromes (MDS) | NPM1 mutations are less common but can occur, often associated with disease progression to AML. | Rare mutations reported in MDS (COSMIC). |
| Lymphoma | NPM1 rearrangements (e.g., with ALK) are seen in anaplastic large-cell lymphoma (ALCL), leading to oncogenic fusion proteins. | NPM1-ALK fusion is a hallmark of ALK+ ALCL (COSMIC). |
| Hepatocellular Carcinoma | Overexpression of NPM1 has been observed, potentially promoting cell proliferation and inhibiting apoptosis. | Expression studies (UniProt, literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Lymph Node | High | High |
| Spleen | High | High |
| Testis | High | High |
| Ovary | High | High |
| Brain | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Lung | Medium | Medium |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | High | Myeloid leukemia cell line |
| HeLa (cervical cancer) | High | Epithelial carcinoma |
| A549 (lung cancer) | Medium | Lung adenocarcinoma |
| HepG2 (liver cancer) | Medium | Hepatocellular carcinoma |
| MCF7 (breast cancer) | Medium | Breast adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Type A (c.863_864insTCTG) | Insertion | ~50-60% of NPM1-mutated AML | Creates NES, cytoplasmic localization |
| Type B (c.860_863dup) | Duplication | ~20-30% | Creates NES, cytoplasmic localization |
| Type C (c.863_864insCATG) | Insertion | ~10-15% | Creates NES, cytoplasmic localization |
| Other rare mutations | Insertion/duplication | ~5% | Similar effect on localization |
Mutation functional classification
Loss of Function (LOF)
Not typically classified as loss-of-function; mutations are usually heterozygous and exert a dominant effect via mislocalization.
Gain of Function (GOF)
Mutations create a novel nuclear export signal, leading to aberrant cytoplasmic accumulation of NPM1, which can be considered a gain of function in terms of altered localization and interaction with cytoplasmic partners.
Dominant Negative (DN)
The mutant NPM1 can heterodimerize with wild-type NPM1, potentially interfering with its nuclear functions, thus acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ribosome biogenesis
• p53/ARF tumor suppressor pathway
• Centrosome duplication
• Histone chaperone activity
• DNA damage response
Protein Summary
Nucleophosmin (NPM1) is a 294-amino acid protein with multiple isoforms. It contains an N-terminal oligomerization domain, a central acidic domain, and a C-terminal nucleic acid-binding domain. It is predominantly nucleolar but shuttles to the cytoplasm. NPM1 functions as a molecular chaperone, participating in ribosome biogenesis, histone assembly, and centrosome duplication. It also regulates the stability and activity of the tumor suppressor p53 via interaction with ARF. Mutations in NPM1, particularly in AML, lead to cytoplasmic mislocalization and altered function, contributing to leukemogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPM1 Knockout HEK293 Cell Line | EDJ-KQ50485 | Human | 4869 | Details Get a Quote |
| NPM1 Knockout HeLa Cell Line | EDJ-KQ54013 | Human | 4869 | Details Get a Quote |
| NPM1 Knockout A-549 Cell Line | EDJ-KQ62504 | Human | 4869 | Details Get a Quote |
| NPM1 Knockout HCT 116 Cell Line | EDJ-KQ70972 | Human | 4869 | Details Get a Quote |
