NPM2

Summary

NPM2 (nucleophosmin/nucleoplasmin 2, HGNC:7930) is a protein-coding gene on chromosome 8p21.3, encoding Nucleoplasmin-2 (Q86SE8). Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development.

Predicted to enable RNA binding activity; chromatin binding activity; and histone binding activity. Involved in several processes, including blastocyst development; oocyte differentiation; and regulation of cell cycle process. Located in chromatin and nucleus.

Source: NCBI Gene 10361 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001286680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7930
Approved symbol	NPM2
Name	nucleophosmin/nucleoplasmin 2
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158806
Ensembl biotype	protein_coding
OMIM	608073
Entrez	10361

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000289820, ENST00000381530, ENST00000397940, ENST00000518119, ENST00000519373, ENST00000520125, ENST00000520180, ENST00000520456, ENST00000521157, ENST00000522813, ENST00000522953, ENST00000524322, ENST00000615914, ENST00000621538, ENST00000962009, ENST00000962010, ENST00000962011

RefSeq mRNA: 12 — MANE Select: NM_001286680 NM_001286680, NM_001286681, NM_001413113, NM_001413114, NM_001413115, NM_001413116, NM_001413117, NM_001413118, NM_001413119, NM_001413120, NM_001413121, NM_182795

CCDS: CCDS6018, CCDS75703

Canonical transcript exons

ENST00000518119 — 10 exons

Exon	Start	End
ENSE00001309267	22025216	22025306
ENSE00001530855	22024134	22024623
ENSE00002131173	22024724	22024830
ENSE00003471133	22034510	22034544
ENSE00003483713	22025647	22025772
ENSE00003507565	22036493	22036526
ENSE00003623601	22033130	22033223
ENSE00003634843	22025436	22025521
ENSE00003643383	22036638	22036897
ENSE00003657127	22034109	22034275

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 96.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9672 / max 100.4753, expressed in 447 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87664	1.2536	334
87663	0.5155	180
87662	0.0835	47
87665	0.0803	51
87666	0.0342	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.87	gold quality
right frontal lobe	UBERON:0002810	96.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.85	gold quality
anterior cingulate cortex	UBERON:0009835	95.37	gold quality
cerebellar hemisphere	UBERON:0002245	95.33	gold quality
cerebellar cortex	UBERON:0002129	95.27	gold quality
prefrontal cortex	UBERON:0000451	95.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.57	gold quality
cerebellum	UBERON:0002037	94.37	gold quality
frontal cortex	UBERON:0001870	93.92	gold quality
oocyte	CL:0000023	93.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.90	gold quality
neocortex	UBERON:0001950	93.44	gold quality
lateral globus pallidus	UBERON:0002476	93.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.86	gold quality
hypothalamus	UBERON:0001898	92.80	gold quality
amygdala	UBERON:0001876	92.76	gold quality
substantia nigra pars compacta	UBERON:0001965	92.44	gold quality
right lobe of thyroid gland	UBERON:0001119	92.41	gold quality
left lobe of thyroid gland	UBERON:0001120	92.30	gold quality
cerebral cortex	UBERON:0000956	91.94	gold quality
primary visual cortex	UBERON:0002436	91.68	gold quality
thyroid gland	UBERON:0002046	91.52	gold quality
substantia nigra	UBERON:0002038	90.77	gold quality
cerebellar vermis	UBERON:0004720	90.70	silver quality
brain	UBERON:0000955	90.68	gold quality
left ventricle myocardium	UBERON:0006566	90.52	gold quality
forebrain	UBERON:0001890	90.49	gold quality
occipital lobe	UBERON:0002021	90.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NPM2, 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-4283	100.00	66.42	2097
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-7973	96.48	65.54	502
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 7)

• Expression of NPM2 in HeLa cells (PMID:12209603)
• Promoter methylation and differential gene expression of five markers: COL1A2, NPM2, HSPB6, DDIT4L and MT1G were validated by sequencing of bisulfite-modified DNA and real-time reverse transcriptase PCR, respectively. (PMID:19491193)
• The crystal structure of a truncated Npm2-core shows that the N-terminal domains of Npm2 and Np form similar pentamers, providing insights into the mechanism of histone binding by nucleoplasmins. (PMID:21863821)
• 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)
• Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases. (PMID:36280841)
• Hexavalent chromium causes centrosome amplification by inhibiting the binding between TMOD2 and NPM2. (PMID:36963620)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	npm2b	ENSDARG00000053963
mus_musculus	Npm2	ENSMUSG00000047911
rattus_norvegicus	Npm2	ENSRNOG00000025638
drosophila_melanogaster	Nlp	FBGN0016685
drosophila_melanogaster	Nph	FBGN0039735

Paralogs (2): NPM3 (ENSG00000107833), NPM1 (ENSG00000181163)

Protein

Protein identifiers

Nucleoplasmin-2 — Q86SE8 (reviewed: Q86SE8)

All UniProt accessions (3): E5RFQ8, E5RGN1, Q86SE8

UniProt curated annotations — full annotation on UniProt →

Function. Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Probably involved in sperm DNA decondensation during fertilization.

Subunit / interactions. Homopentamer, when bound to H2A-H2B dimers only. Homodecamer of two stacked pentamers, when bound to H2A-H2B dimers and H3-H4 tetramers simultaneously.

Subcellular location. Nucleus.

Domain organisation. The acidic tract A2 mediates histone binding.

Similarity. Belongs to the nucleoplasmin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86SE8-1	1	yes
Q86SE8-2	2

RefSeq proteins (12): NP_001273609, NP_001273610, NP_001400042, NP_001400043, NP_001400044, NP_001400045, NP_001400046, NP_001400047, NP_001400048, NP_001400049, NP_001400050, NP_877724 (=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 (19 total): strand 8, compositionally biased region 3, region of interest 2, site 2, chain 1, turn 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3T30	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SE8-F1	73.36	0.43

Functional residue map

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

Catalytic / active sites (2): 57 (interaction between pentamers); 84 (interaction between pentamers)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9821993	Replacement of protamines by nucleosomes in the male pronucleus

MSigDB gene sets: 77 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_OOGENESIS, GOBP_REGULATION_OF_EXIT_FROM_MITOSIS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_MEIOTIC_CELL_CYCLE, RICKMAN_METASTASIS_DN, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ORGANELLE_FISSION

GO Biological Process (9): blastocyst development (GO:0001824), chromatin remodeling (GO:0006338), regulation of exit from mitosis (GO:0007096), single fertilization (GO:0007338), oocyte differentiation (GO:0009994), positive regulation of DNA replication (GO:0045740), positive regulation of meiotic nuclear division (GO:0045836), chromatin organization (GO:0006325), positive regulation of DNA metabolic process (GO:0051054)

GO Molecular Function (6): chromatin binding (GO:0003682), RNA binding (GO:0003723), enzyme binding (GO:0019899), histone binding (GO:0042393), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
cellular anatomical structure	3
binding	2
nuclear lumen	2
in utero embryonic development	1
anatomical structure development	1
chromatin organization	1
exit from mitosis	1
regulation of mitotic cell cycle phase transition	1
fertilization	1
developmental process involved in reproduction	1
cell differentiation	1
oogenesis	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
regulation of meiotic nuclear division	1
positive regulation of meiotic cell cycle	1
positive regulation of nuclear division	1
positive regulation of cell cycle process	1
meiotic nuclear division	1
cellular component organization	1
DNA metabolic process	1
positive regulation of macromolecule metabolic process	1
regulation of DNA metabolic process	1
nucleic acid binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPM2	ZAR1	Q86SH2	641
NPM2	KPNA7	A9QM74	622
NPM2	H2AC20	Q16777	582
NPM2	H2AC19	P20670	582
NPM2	H2BC21	Q16778	552
NPM2	H1-8	Q8IZA3	519
NPM2	ALK	Q9UM73	515
NPM2	OSCP1	Q8WVF1	448
NPM2	NLRP5	P59047	448
NPM2	ZAR1L	A6NP61	431
NPM2	NUCLEOLIN	P19338	426
NPM2	TICRR	Q7Z2Z1	414
NPM2	MECP2	P51608	400
NPM2	CDC25C	P30307	392
NPM2	ZNF879	B4DU55	370

IntAct

26 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
NPM2	NPM1	psi-mi:“MI:0915”(physical association)	0.740
NPM1	NPM2	psi-mi:“MI:0915”(physical association)	0.740
NPM2	NPM1	psi-mi:“MI:0914”(association)	0.740
SDCBP2	NPM2	psi-mi:“MI:0915”(physical association)	0.670
NPM2	SDCBP2	psi-mi:“MI:0915”(physical association)	0.670
PLEKHF2	NPM2	psi-mi:“MI:0915”(physical association)	0.560
NPM2	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
NPM2	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Cdkn2a	NPM2	psi-mi:“MI:0915”(physical association)	0.400
NPM2	NPM1	psi-mi:“MI:0915”(physical association)	0.370
ODF2L	GAPDHS	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): NPM2 (Two-hybrid), NPM2 (Two-hybrid), SDCBP2 (Two-hybrid), PLEKHF2 (Two-hybrid), NPM1 (Affinity Capture-MS), GOPC (Affinity Capture-MS), C1QBP (Affinity Capture-MS), NPM3 (Affinity Capture-MS), NPM2 (Affinity Capture-MS), MTG2 (Affinity Capture-MS), NPM2 (Two-hybrid), PLEKHF1 (Two-hybrid), PLEKHF2 (Two-hybrid), NPM1 (Two-hybrid), C1QBP (Affinity Capture-MS)

ESM2 similar proteins: B8AW64, B8B2R4, B8B4K9, B9FU45, O42584, O59797, O74191, P05221, P06748, P07222, P0CP98, P0CP99, P13084, P16039, P38911, P53997, P54397, P78920, P91753, Q00PI9, Q06205, Q10175, Q17LZ2, Q18240, Q1HTZ8, Q1HTZ9, Q24168, Q27415, Q2TA40, Q3T160, Q45FF9, Q53WK4, Q5U2Z3, Q5VND6, Q61937, Q70Z16, Q70Z17, Q70Z18, Q70Z19, Q78ZA7

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1233 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22024827:GACA:G	donor_gain	1.0000
8:22024831:G:GG	donor_gain	1.0000
8:22025432:GCAG:G	acceptor_loss	1.0000
8:22025434:A:AG	acceptor_gain	1.0000
8:22025434:AG:A	acceptor_gain	1.0000
8:22025434:AGG:A	acceptor_loss	1.0000
8:22025434:AGGCT:A	acceptor_gain	1.0000
8:22025435:G:GA	acceptor_gain	1.0000
8:22025435:GG:G	acceptor_gain	1.0000
8:22025435:GGC:G	acceptor_gain	1.0000
8:22025435:GGCT:G	acceptor_gain	1.0000
8:22025435:GGCTG:G	acceptor_gain	1.0000
8:22025520:CGGTA:C	donor_loss	1.0000
8:22025522:G:GG	donor_gain	1.0000
8:22025522:GTA:G	donor_loss	1.0000
8:22025755:GCC:G	donor_gain	1.0000
8:22025795:G:GT	donor_gain	1.0000
8:22033125:TGCA:T	acceptor_loss	1.0000
8:22033126:GCA:G	acceptor_loss	1.0000
8:22033127:CA:C	acceptor_loss	1.0000
8:22034500:T:TA	acceptor_gain	1.0000
8:22024722:A:AG	acceptor_gain	0.9900
8:22024723:G:GG	acceptor_gain	0.9900
8:22025431:C:CA	acceptor_gain	0.9900
8:22025635:A:AG	acceptor_gain	0.9900
8:22025643:TCAGA:T	acceptor_loss	0.9900
8:22025644:CAGAT:C	acceptor_loss	0.9900
8:22025645:A:AG	acceptor_gain	0.9900
8:22025645:AG:A	acceptor_loss	0.9900
8:22025646:G:GC	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000081110 (8:22027510 A>G,T), RS1000232951 (8:22033385 G>C,T), RS1000342335 (8:22029836 T>C), RS1000375747 (8:22023923 G>A,T), RS1000557526 (8:22027716 C>G), RS1000685157 (8:22024147 C>T), RS1001112320 (8:22028841 T>G), RS1001152709 (8:22029134 C>T), RS1001321943 (8:22023590 C>G,T), RS1001342233 (8:22028463 C>A,G,T), RS1001514771 (8:22034008 C>T), RS1001601738 (8:22028070 G>T), RS1001734531 (8:22035628 A>G), RS1001819140 (8:22024708 C>T), RS1001898467 (8:22022829 A>G,T)

Disease associations

OMIM: gene MIM:608073 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_371	Obesity-related traits	5.000000e-06
GCST010002_271	Refractive error	2.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, decreases methylation	2
Estradiol	decreases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
bisphenol A	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Decitabine	decreases methylation	1
Arsenic	increases expression	1
Caffeine	increases phosphorylation	1
Endosulfan	increases expression	1
Methapyrilene	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	affects expression	1

Clinical trials (associated diseases)

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