NPM1

nucleophosmin 1

Basic information

Region (hg38): 5:171387116-171411810

Links

ENSG00000181163 ∙ NCBI:4869 ∙ OMIM:164040 ∙ HGNC:7910 ∙ Uniprot:P06748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPM1 gene.

• Acute myeloid leukemia (2 variants)
• Myelodysplastic syndrome progressed to acute myeloid leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			2			2
nonsense						0
start loss						0
frameshift	2					2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding					13	13
Total	2	0	3	4	14

Variants in NPM1

This is a list of pathogenic ClinVar variants found in the NPM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-171387358-A-T			Benign (Jun 20, 2021)
5-171387948-G-T		not specified	not provided (Sep 19, 2013)
5-171387987-G-A		NPM1-related disorder	Likely benign (Jun 10, 2019)
5-171388121-G-T			Benign (Nov 12, 2018)
5-171390082-C-T			Likely benign (Oct 01, 2023)
5-171391343-T-C		NPM1-related disorder	Likely benign (Mar 13, 2019)
5-171391358-A-G		NPM1-related disorder	Likely benign (Apr 03, 2024)
5-171392502-C-A			Benign (Jun 20, 2021)
5-171392586-CTTT-C			Benign (Jun 20, 2021)
5-171392603-T-A			Benign (Nov 12, 2018)
5-171392719-A-G		not specified	not provided (Sep 19, 2013)
5-171392785-C-G		not specified	not provided (Sep 19, 2013)
5-171392883-G-A			Benign (Nov 12, 2018)
5-171392927-TTGC-T		not specified	not provided (Sep 19, 2013)
5-171392946-TGAC-T		NPM1-related disorder	Uncertain significance (May 21, 2024)
5-171392949-C-T		NPM1-related disorder	Benign (May 31, 2018)
5-171392964-GGAT-G		NPM1-related disorder	Uncertain significance (Oct 05, 2022)
5-171392967-T-G		not specified	Uncertain significance (Aug 10, 2021)
5-171392976-A-G		not specified	Benign (Jun 06, 2022)
5-171393020-G-A			Benign (Nov 12, 2018)
5-171400111-C-A			Benign (Jun 19, 2021)
5-171400114-A-G			Benign (Nov 12, 2018)
5-171400152-GTGA-G			Uncertain significance (Nov 22, 2019)
5-171400160-G-C			Uncertain significance (Nov 22, 2019)
5-171400171-T-C		not specified • Acute myeloid leukemia	Benign/Likely benign (Apr 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPM1	protein_coding	protein_coding	ENST00000296930	11	24022

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00184	124610	0	2	124612	0.00000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	84	152	0.554	0.00000720	1959
Missense in Polyphen		3	20.679	0.14507		355
Synonymous	-1.84	67	50.4	1.33	0.00000251	489
Loss of Function	3.97	0	18.4	0.00	8.74e-7	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000555	0.0000552
Finnish	0.00	0.00
European (Non-Finnish)	0.00000996	0.00000891
Middle Eastern	0.0000555	0.0000552
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double- stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). {ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
• Disease: DISEASE: Note=A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. {ECO:0000269|PubMed:8122112, ECO:0000269|PubMed:8633037}.; DISEASE: Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. {ECO:0000269|PubMed:8562957}.; DISEASE: Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. {ECO:0000269|PubMed:8570204}.; DISEASE: Note=Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C- terminus of the protein are associated with an aberrant cytoplasmic location. {ECO:0000269|PubMed:15659725}.
• Pathway: Disease;Gene expression (Transcription);Generic Transcription Pathway;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;RNA Polymerase II Transcription;Infectious disease;Nucleosome assembly;Chromosome Maintenance;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain;TP53 Regulates Transcription of Cell Cycle Genes;Deposition of new CENPA-containing nucleosomes at the centromere;Transcriptional Regulation by TP53;TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Nuclear import of Rev protein;Cell Cycle;Aurora B signaling;Validated targets of C-MYC transcriptional activation;BARD1 signaling events;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.579

Intolerance Scores

• loftool: 0.523
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.700
• hipred: Y
• hipred_score: 0.811
• ghis: 0.700

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Npm1
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; embryo phenotype; liver/biliary system phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: npm1b
• Affected structure: myeloid cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: ribosomal large subunit export from nucleus;ribosomal small subunit export from nucleus;DNA repair;nucleosome assembly;chromatin remodeling;regulation of transcription by RNA polymerase II;rRNA export from nucleus;intracellular protein transport;nucleocytoplasmic transport;centrosome cycle;signal transduction;cell aging;protein localization;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of centrosome duplication;negative regulation of centrosome duplication;viral process;regulation of endodeoxyribonuclease activity;CENP-A containing nucleosome assembly;cellular response to UV;ribosome assembly;ribosomal large subunit biogenesis;ribosomal small subunit biogenesis;negative regulation of apoptotic process;negative regulation of protein kinase activity by regulation of protein phosphorylation;positive regulation of translation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of centriole replication;positive regulation of NF-kappaB transcription factor activity;protein complex oligomerization;regulation of endoribonuclease activity;regulation of eIF2 alpha phosphorylation by dsRNA;regulation of mRNA stability involved in cellular response to UV;positive regulation of cell cycle G2/M phase transition
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;centrosome;cytosol;focal adhesion;membrane;spindle pole centrosome;protein-containing complex;protein-DNA complex;ribonucleoprotein complex
• Molecular function: core promoter binding;chromatin binding;transcription coactivator activity;RNA binding;protein kinase inhibitor activity;protein binding;transcription factor binding;protein kinase binding;Tat protein binding;activating transcription factor binding;histone binding;protein homodimerization activity;ribosomal large subunit binding;ribosomal small subunit binding;protein heterodimerization activity;NF-kappaB binding;unfolded protein binding