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URL of this page: https://medlineplus.gov/genetics/gene/npm1/

NPM1 gene

nucleophosmin 1

Normal Function

The NPM1 gene provides instructions for making a protein called nucleophosmin, which is found in a small region inside the nucleus of the cell called the nucleolus. Nucleophosmin is the most abundant protein in the nucleolus; it shuttles back and forth between the nucleus and the surrounding fluid (the cytoplasm). Nucleophosmin is thought to play a role in many cellular processes, including protein formation; DNA repair; and the cell cycle, which is the step-by-step process by which cells replicate. The protein also plays a role in helping cells respond to disruptions in the function or structure of the nucleolus (nucleolar stress).

In the nucleolus, nucleophosmin interacts with other proteins, including p14ARF and MDM2. These interactions are involved with tumor suppressor pathways, which prevent cells from growing and dividing in an uncontrolled way.

Health Conditions Related to Genetic Changes

Cytogenetically normal acute myeloid leukemia

Genetic changes that contribute to disease are called pathogenic variants. Pathogenic variants in the NPM1 gene are found in people with a form of cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). CN-AML is a type of acute myeloid leukemia (AML), which is a cancer of the blood and blood-forming tissue (bone marrow). People with CN-AML do not appear to have the large chromosomal abnormalities that are sometimes involved in the development of AML. About half of individuals with CN-AML have a pathogenic variant in the NPM1 gene.

The pathogenic variants in the NPM1 gene that are involved in CN-AML are acquired during a person's lifetime (somatic) and are only found in cancer cells. In people with CN-AML, most of the somatic variants in the NPM1 gene occur in a region near the end of the protein called exon 12. These variants alter the protein’s localization signal, which means that the protein does not go where it is supposed to go in the cell. As a result, the altered NPM1 protein stays in the cytoplasm rather than moving into the nucleus where it is needed.

It is not clear exactly how the altered protein contributes to the development of CN-AML. Research suggests that the relocation of the altered protein interferes with the interaction between nucleophosmin and p14ARF, which disrupts a tumor suppressor pathway. This likely impairs the normal maturation (differentiation) of cells called hematopoietic stem cells and contributes to the development of CN-AML. Additional pathways, such as DNA repair pathways, may also be affected. Pathogenic variants in other genes, such as FLT3, IDH1, and IDH2, work together with pathogenic variants in the NPM1 gene to cause CN-AML.

Identifying an NPM1 pathogenic variant in people who are diagnosed with CN-AML can help classify the CN-AML, predict the course and outcome (prognosis) of the cancer, and determine which treatment to use.

More About This Health Condition

Acute promyelocytic leukemia

MedlinePlus Genetics provides information about Acute promyelocytic leukemia

More About This Health Condition

Other cancers

A genetic rearrangement (translocation) that involves the NPM1 gene is found in another blood cell cancer known as anaplastic large cell lymphoma (ALCL). In people with ALCL, white blood cells known as T cells grow and divide uncontrollably and often form tumors in the lymph nodes. The translocation involved in this cancer, known as t(2;5), fuses part of the NPM1 gene on chromosome 5 with part of another gene called ALK on chromosome 2. This rearrangement is somatic and is only present in cancer cells.

The protein produced from the fusion gene is called NPM1::ALK. Like the normal ALK protein, NPM1::ALK turns on signaling pathways that stimulate cell growth and division (proliferation) and differentiation. Unlike ALK, the NPM1::ALK protein is overactive, which can lead to the uncontrolled proliferation of T cells and the development of ALCL.

Other Names for This Gene

  • nucleolar phosphoprotein B23 
  • nucleophosmin
  • nucleophosmin/nucleoplasmin family, member 1
  • numatrin

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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