NPM3

Summary

NPM3 (nucleophosmin/nucleoplasmin 3, HGNC:7931) is a protein-coding gene on chromosome 10q24.32, encoding Nucleoplasmin-3 (O75607). Plays a role in the regulation of diverse cellular processes such as ribosome biogenesis, chromatin remodeling or protein chaperoning.

The protein encoded by this gene is related to the nuclear chaperone phosphoproteins, nucleoplasmin and nucleophosmin. This protein is strongly expressed in diverse cell types where it localizes primarily to the nucleus. Based on its similarity to nucleoplasmin and nucleophosmin, this protein likely functions as a molecular chaperone in the cell nucleus.

Source: NCBI Gene 10360 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_006993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7931
Approved symbol	NPM3
Name	nucleophosmin/nucleoplasmin 3
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107833
Ensembl biotype	protein_coding
OMIM	606456
Entrez	10360

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000370110, ENST00000462391, ENST00000468544, ENST00000474993, ENST00000919538, ENST00000919539, ENST00000919540, ENST00000919541, ENST00000919542, ENST00000919543, ENST00000919544, ENST00000919545

RefSeq mRNA: 1 — MANE Select: NM_006993 NM_006993

CCDS: CCDS7519

Canonical transcript exons

ENST00000370110 — 6 exons

Exon	Start	End
ENSE00001857522	101781325	101781632
ENSE00003463844	101782478	101782597
ENSE00003533876	101782258	101782351
ENSE00003591564	101782839	101782924
ENSE00003630031	101781727	101781854
ENSE00003978278	101783273	101783446

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.5892 / max 420.7640, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111102	38.5892	1805

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.27	gold quality
stromal cell of endometrium	CL:0002255	96.05	gold quality
secondary oocyte	CL:0000655	94.97	gold quality
lower esophagus mucosa	UBERON:0035834	92.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.59	gold quality
body of pancreas	UBERON:0001150	91.40	gold quality
mucosa of transverse colon	UBERON:0004991	90.55	gold quality
islet of Langerhans	UBERON:0000006	90.11	gold quality
pancreas	UBERON:0001264	89.60	gold quality
left adrenal gland cortex	UBERON:0035825	88.85	gold quality
right adrenal gland	UBERON:0001233	88.83	gold quality
esophagus mucosa	UBERON:0002469	88.80	gold quality
left adrenal gland	UBERON:0001234	88.65	gold quality
right adrenal gland cortex	UBERON:0035827	88.64	gold quality
ectocervix	UBERON:0012249	88.54	gold quality
left ovary	UBERON:0002119	88.36	gold quality
right testis	UBERON:0004534	88.26	gold quality
cortical plate	UBERON:0005343	88.15	gold quality
left testis	UBERON:0004533	88.06	gold quality
prefrontal cortex	UBERON:0000451	87.89	gold quality
right ovary	UBERON:0002118	87.81	gold quality
ovary	UBERON:0000992	87.15	gold quality
metanephros cortex	UBERON:0010533	87.12	gold quality
rectum	UBERON:0001052	87.10	gold quality
adrenal cortex	UBERON:0001235	86.94	gold quality
endocervix	UBERON:0000458	86.86	gold quality
adenohypophysis	UBERON:0002196	86.84	gold quality
testis	UBERON:0000473	86.77	gold quality
adrenal gland	UBERON:0002369	86.57	gold quality
body of uterus	UBERON:0009853	86.56	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	27.47
E-HCAD-13	yes	24.88
E-HCAD-6	yes	22.65
E-ANND-3	yes	4.47
E-MTAB-6524	no	287.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

27 targeting NPM3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-561-5P	98.25	68.13	1365

Literature-anchored findings (GeneRIF, showing 7)

• Acetylation of transition protein 2 (TP2) by KAT3B (p300) alters its DNA condensation property and interaction with putative histone chaperone NPM3. (PMID:19710011)
• NPM3 lacks intrinsic histone chaperone activity, inhibits histone assembly activity of NPM1 in vitro, and dramatically enhances transcription in a cellular system. (PMID:20073534)
• Characterization of the sperm chromatin decondensation and nucleosome assembly activities of homo- and hetero-oligomers of NPM1,NPM2 and NPM3. (PMID:22362753)
• Studies indicate that histone chalerones nucleoplasmin (NPM2/NPM3) preferentially associated with histones H2A-H2B in the egg and the nuclear autoantigenic sperm protein (NASP) families. (PMID:22968912)
• NPM3 as a novel oncogenic factor and poor prognostic marker contributes to cell proliferation and migration in lung adenocarcinoma. (PMID:37254219)
• Pumilio1 regulates NPM3/NPM1 axis to promote PD-L1-mediated immune escape in gastric cancer. (PMID:38029539)
• Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer. (PMID:39300184)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	npm3	ENSDARG00000103594
mus_musculus	Npm3	ENSMUSG00000056209
rattus_norvegicus	Npm3	ENSRNOG00000017622
drosophila_melanogaster	Nlp	FBGN0016685
drosophila_melanogaster	Nph	FBGN0039735

Paralogs (2): NPM2 (ENSG00000158806), NPM1 (ENSG00000181163)

Protein

Protein identifiers

Nucleoplasmin-3 — O75607 (reviewed: O75607)

All UniProt accessions (1): O75607

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of diverse cellular processes such as ribosome biogenesis, chromatin remodeling or protein chaperoning. Modulates the histone chaperone function and the RNA-binding activity of nucleolar phosphoprotein B23/NPM. Efficiently mediates chromatin remodeling when included in a pentamer containing NPM3 and NPM.

Subunit / interactions. Interacts with NPM (via N-terminus). Forms a pentamer with NPM at a ratio 4:1 (NPM3/NPM). Two pentamers form a decamer.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated.

Similarity. Belongs to the nucleoplasmin family.

RefSeq proteins (1): NP_008924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004301	Nucleoplasmin	Family
IPR024057	Nucleoplasmin_core_dom	Domain
IPR036824	Nucleoplasmin_core_dom_sf	Homologous_superfamily

Pfam: PF03066

UniProt features (15 total): modified residue 7, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75607-F1	80.58	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 158, 2, 13, 16, 27, 147, 151

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_16, GOBP_RRNA_TRANSCRIPTION, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, PAX8_B, MARTINEZ_RB1_TARGETS_DN, MORF_PRKDC, HFH1_01, PIT1_Q6, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GOBP_CHROMATIN_REMODELING, MARTINEZ_RB1_AND_TP53_TARGETS_UP

GO Biological Process (3): chromatin remodeling (GO:0006338), rRNA processing (GO:0006364), rRNA transcription (GO:0009303)

GO Molecular Function (4): chromatin binding (GO:0003682), RNA binding (GO:0003723), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
rRNA metabolic process	2
binding	2
nuclear lumen	2
chromatin organization	1
RNA processing	1
ribosome biogenesis	1
DNA-templated transcription	1
nucleic acid binding	1
protein binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPM3	FGF8	P55075	662
NPM3	NPM1	P06748	652
NPM3	TMEM167A	Q8TBQ9	517
NPM3	H2AC20	Q16777	501
NPM3	H2AC19	P20670	501
NPM3	H2BC21	Q16778	488
NPM3	CFAP20DC	Q6ZVT6	422
NPM3	SETSIP	P0DME0	420
NPM3	C3orf38	Q5JPI3	417
NPM3	VGLL4	Q14135	402
NPM3	FUBP1	Q96AE4	390
NPM3	FBXW4	P57775	386
NPM3	MPG	P29372	363
NPM3	OGA	O60502	352
NPM3	CPSF4L	A6NMK7	350

IntAct

57 interactions, top by confidence:

A	B	Type	Score
NPM2	NPM3	psi-mi:“MI:0915”(physical association)	0.800
NPM2	NPM3	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
NPM3	UPRT	psi-mi:“MI:0915”(physical association)	0.560
tat	AHCYL1	psi-mi:“MI:0914”(association)	0.560
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
tat	NPM3	psi-mi:“MI:0915”(physical association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CRK	NPM3	psi-mi:“MI:0407”(direct interaction)	0.440
WT1	NPM3	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Naa11		psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
MAB21L2	PTBP1	psi-mi:“MI:0914”(association)	0.350
TCF7L2	LOC401309	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NPM1	NVL	psi-mi:“MI:0914”(association)	0.350
MAP2K3	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (329): NPM2 (Two-hybrid), NPM3 (Affinity Capture-MS), NPM3 (Affinity Capture-MS), ARGLU1 (Co-fractionation), ATP5B (Co-fractionation), EEF1G (Co-fractionation), NCL (Co-fractionation), NPM1 (Co-fractionation), NPM3 (Co-fractionation), NPM3 (Co-fractionation), TPD52L1 (Co-fractionation), YWHAE (Co-fractionation), NPM3 (Proximity Label-MS), NPM3 (Proximity Label-MS), NPM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A494C1R9, A5A6J5, A5PJX4, A6NKD2, F1M5F3, O75607, P0CV98, P0CV99, P0CW00, P0CW01, P49796, P54368, P56182, Q0VCT3, Q15014, Q2HJ93, Q2KJ58, Q3U3N0, Q496Y0, Q4R4I0, Q4R578, Q58DT5, Q5C9Z4, Q5EAN7, Q5R905, Q5RC37, Q5XIX3, Q62865, Q80YR4, Q86UK7, Q8BSI6, Q8C4S8, Q8CHT6, Q8HXH0, Q8IYL2, Q8K4J0, Q8N344, Q8VBT9, Q8VDV3, Q8VIP2

Diamond homologs: O42584, O75607, P05221, P06748, P07222, P13084, P16039, P91753, Q1HTZ8, Q1HTZ9, Q27415, Q3T160, Q5RC37, Q61937, Q80W85, Q86SE8, Q9CPP0, Q9NLA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Influenza Viral RNA Transcription and Replication	5	28.4×	7e-05
Influenza Infection	6	27.7×	2e-05
SARS-CoV-1-host interactions	5	23.1×	2e-04
rRNA processing in the nucleus and cytosol	5	21.2×	2e-04
rRNA processing	5	19.3×	2e-04
Peptide chain elongation	5	16.7×	3e-04
Viral mRNA Translation	5	16.7×	3e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	16.5×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	6	25.8×	3e-05
cytoplasmic translation	5	17.5×	1e-03
translation	8	15.5×	2e-05
rRNA processing	5	13.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

33 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

721 predictions. Top by Δscore:

Variant	Effect	Δscore
10:101781630:GACC:G	acceptor_loss	1.0000
10:101781785:A:C	donor_gain	1.0000
10:101781788:T:TA	donor_gain	1.0000
10:101781791:T:TA	donor_gain	1.0000
10:101781850:CGTAA:C	acceptor_gain	1.0000
10:101781851:GTAA:G	acceptor_gain	1.0000
10:101781852:TAA:T	acceptor_gain	1.0000
10:101781853:AA:A	acceptor_gain	1.0000
10:101781854:AC:A	acceptor_loss	1.0000
10:101781855:C:CC	acceptor_gain	1.0000
10:101781856:T:G	acceptor_loss	1.0000
10:101781858:G:GC	acceptor_gain	1.0000
10:101781863:C:CT	acceptor_gain	1.0000
10:101781865:C:CT	acceptor_gain	1.0000
10:101781868:A:T	acceptor_gain	1.0000
10:101782246:C:A	donor_gain	1.0000
10:101782347:CTGAG:C	acceptor_gain	1.0000
10:101782350:AGCTG:A	acceptor_loss	1.0000
10:101782351:GCTG:G	acceptor_loss	1.0000
10:101782352:C:CC	acceptor_gain	1.0000
10:101782352:C:CG	acceptor_loss	1.0000
10:101782353:T:A	acceptor_loss	1.0000
10:101782473:CTCA:C	donor_loss	1.0000
10:101782475:CAC:C	donor_loss	1.0000
10:101782476:A:AC	donor_gain	1.0000
10:101782476:AC:A	donor_gain	1.0000
10:101782476:ACCAT:A	donor_loss	1.0000
10:101782477:C:CA	donor_gain	1.0000
10:101782477:CC:C	donor_gain	1.0000
10:101782477:CCA:C	donor_gain	1.0000

AlphaMissense

1170 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:101782272:C:T	G135E	0.999
10:101782311:A:G	F122S	0.999
10:101782273:C:A	G135W	0.998
10:101782290:C:T	G129D	0.997
10:101782296:C:A	G127V	0.997
10:101782296:C:T	G127D	0.997
10:101782500:A:G	L101P	0.997
10:101782500:A:T	L101H	0.997
10:101782506:G:T	A99D	0.997
10:101782305:A:G	L124P	0.996
10:101782515:A:T	V96D	0.996
10:101782915:A:T	L43H	0.996
10:101782272:C:A	G135V	0.995
10:101782284:A:T	V131E	0.995
10:101782335:A:G	F114S	0.995
10:101782290:C:A	G129V	0.994
10:101782291:C:G	G129R	0.994
10:101782334:G:C	F114L	0.994
10:101782334:G:T	F114L	0.994
10:101782336:A:G	F114L	0.994
10:101782562:A:C	N80K	0.994
10:101782562:A:T	N80K	0.994
10:101782887:A:C	F52L	0.994
10:101782887:A:T	F52L	0.994
10:101782889:A:G	F52L	0.994
10:101782273:C:G	G135R	0.993
10:101782273:C:T	G135R	0.993
10:101782317:A:T	V120E	0.993
10:101783274:G:C	F39L	0.993
10:101783274:G:T	F39L	0.993

dbSNP variants (sampled 300 via entrez): RS1000082932 (10:101783786 G>C), RS1000454672 (10:101783945 A>G), RS1000514804 (10:101785269 C>T), RS1000914572 (10:101785083 C>A), RS1001140684 (10:101784439 CACG>C), RS1001170440 (10:101784242 C>T), RS1001513529 (10:101783815 C>T), RS1002519707 (10:101782642 T>G), RS1002571963 (10:101782896 G>A), RS1003524842 (10:101781249 G>A,C), RS1003577185 (10:101781458 T>C,G), RS1004921806 (10:101783007 A>C,G), RS1005861203 (10:101781872 A>G), RS1006216866 (10:101781277 G>A,T), RS1007705152 (10:101784634 T>C)

Disease associations

OMIM: gene MIM:606456 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005316_348	Intelligence (MTAG)	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
TAK-243	increases sumoylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Aminoglutethimide	decreases expression	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3CN	Abcam HEK293T NPM3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.