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Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene. NPM1 is associated with nucleolar ribonucleoprotein structures and binds single-stranded. Install terminus-altair in the available plugins and restart. Select Altair in Theme settings. Hyper-altair - Hyper version; terminus-altair - Terminus version; vscode-altair - VS Code version; Contribute. Altair is based on Bootstrap 4, styles are located in the theme.scss file. Clone this repository and run: npm install.

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 shuttles back and forth between the nucleus and the fluid surrounding it (the cytoplasm). It is thought to play a part in many cellular functions, including processes involved in protein formation, DNA replication, and the progression of the cell through the step-by-step process it takes to replicate itself (called the cell cycle). In the nucleolus, nucleophosmin attaches to another protein called ARF, keeping it in the proper location and protecting it from being broken down. The ARF protein is considered a tumor suppressor because it is involved in pathways that prevent cells from growing and dividing in an uncontrolled way.

Health Conditions Related to Genetic Changes

Acute promyelocytic leukemia

MedlinePlus Genetics provides information about Acute promyelocytic leukemia

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More About This Health Condition

Cytogenetically normal acute myeloid leukemia

Mutations in the NPM1 gene are involved in a form of blood cell cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML. Approximately 64 percent of people with CN-AML have a mutation in the NPM1 gene.

The NPM1 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations occur in a region of the gene designated exon 12. They change the blueprint used to make the nucleophosmin protein, leading to production of a protein with an altered sequence of protein building blocks (amino acids). The alterations change the amino acid tryptophan at protein position 290 and often the tryptophan at position 288. These two tryptophans are important for localization of the protein in the nucleolus. The new sequence also provides a signal (called the nuclear export signal) for the protein to be moved out of the nucleus. As a result, the nucleophosmin protein is found in the cytoplasm rather than the nucleolus.

It is not clear how abnormal localization of the nucleophosmin protein leads to acute myeloid leukemia. Research suggests that it affects the function of the ARF protein. Because of its interaction with the altered nucleophosmin, the ARF protein is also found in the cytoplasm in cells with these genetic changes. In addition, the altered nucleophosmin protein is unable to protect ARF from being broken down. A reduction of the tumor suppressor function of the ARF protein is believed to lead to the uncontrolled production of abnormal white blood cells that occurs in acute myeloid leukemia. Other effects of NPM1 gene mutations may also be involved in the development of leukemia.

More About This Health Condition

Other cancers

A genetic rearrangement (translocation) involving the NPM1 gene is found in another blood cell cancer known as anaplastic large cell lymphoma (ALCL). In 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 a somatic mutation.

The protein produced from the fusion gene is called NPM-ALK. Like the normal activated ALK protein, NPM-ALK turns on signaling pathways that stimulate cell growth and division (proliferation) and maturation (differentiation). Unlike ALK, the NPM-ALK protein is active all the time, which causes uncontrolled cell proliferation and leads to ALCL.

Other Names for This Gene

• B23
• NPM
• NPM_HUMAN
• nucleolar protein NO38
• nucleophosmin
• nucleophosmin (nucleolar phosphoprotein B23, numatrin)
• nucleophosmin/nucleoplasmin family, member 1

Additional Information & Resources

Terminus Meaning

Tests Listed in the Genetic Testing Registry

• Tests of NPM1

Catalog of Genes and Diseases from OMIM

References

Terminus Npm Location

Terminus Name Meaning

• Colombo E, Martinelli P, Zamponi R, Shing DC, Bonetti P, Luzi L, Volorio S,Bernard L, Pruneri G, Alcalay M, Pelicci PG. Delocalization and destabilizationof the Arf tumor suppressor by the leukemia-associated NPM mutant. Cancer Res.2006 Mar 15;66(6):3044-50. Citation on PubMed
• Falini B, Bolli N, Shan J, Martelli MP, Liso A, Pucciarini A, Bigerna B,Pasqualucci L, Mannucci R, Rosati R, Gorello P, Diverio D, Roti G, Tiacci E,Cazzaniga G, Biondi A, Schnittger S, Haferlach T, Hiddemann W, Martelli MF, Gu W,Mecucci C, Nicoletti I. Both carboxy-terminus NES motif and mutated tryptophan(s)are crucial for aberrant nuclear export of nucleophosmin leukemic mutants inNPMc+ AML. Blood. 2006 Jun 1;107(11):4514-23. Epub 2006 Feb 2. Citation on PubMed
• Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La StarzaR, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A,Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F,Pelicci PG, Martelli MF; GIMEMA Acute Leukemia Working Party. Cytoplasmicnucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl JMed. 2005 Jan 20;352(3):254-66. Erratum in: N Engl J Med. 2005 Feb 17;352(7):740. Citation on PubMed
• Falini B, Nicoletti I, Bolli N, Martelli MP, Liso A, Gorello P, Mandelli F,Mecucci C, Martelli MF. Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias. Haematologica. 2007 Apr;92(4):519-32.Review. Citation on PubMed
• Li J, Sejas DP, Rani R, Koretsky T, Bagby GC, Pang Q. Nucleophosmin regulates cell cycle progression and stress response in hematopoietic stem/progenitorcells. J Biol Chem. 2006 Jun 16;281(24):16536-45. Epub 2006 Apr 11. Citation on PubMed