NPM1

Summary

NPM1 (nucleophosmin 1, HGNC:7910) is a protein-coding gene on chromosome 5q35.1, encoding Nucleophosmin (P06748). 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. In precision oncology, NPM1 EXON 11 MUTATION confers sensitivity to Tretinoin in Acute Myeloid Leukemia (CIViC Level B); 10 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 81.3% of cell lines).

The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified.

Source: NCBI Gene 4869 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyskeratosis congenita (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 97 total — 8 pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 10 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 99
• Drug target: yes — 2 via a complex or family; 5 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 2 — Ceritinib, Crizotinib (NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor))
• Precision-oncology evidence (CIViC): 11 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 81.3% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.31 (highly constrained)
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_002520
• Interaction hub: 5,060 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7910
Approved symbol	NPM1
Name	nucleophosmin 1
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	B23, NPM
Ensembl gene	ENSG00000181163
Ensembl biotype	protein_coding
OMIM	164040
Entrez	4869

Gene structure

Transcript identifiers

Ensembl transcripts: 94 — 57 protein_coding, 21 nonsense_mediated_decay, 16 retained_intron

MANE Select: ENST00000296930

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 6, TSL 3: 1, TSL 5: 1

ENST00000296930, ENST00000351986, ENST00000393820, ENST00000517671, ENST00000518587, ENST00000519955, ENST00000521260, ENST00000521672, ENST00000521710, ENST00000523339, ENST00000523622, ENST00000524204, ENST00000676504, ENST00000676589, ENST00000676613, ENST00000676625, ENST00000677297, ENST00000677325, ENST00000677357, ENST00000677467, ENST00000677600, ENST00000677672, ENST00000677682, ENST00000677741, ENST00000677904, ENST00000677907, ENST00000678186, ENST00000678267, ENST00000678280, ENST00000678774, ENST00000679006, ENST00000679190, ENST00000679233, ENST00000867397, ENST00000867398, ENST00000923456, ENST00000923457, ENST00000923458, ENST00000923459, ENST00000923460, ENST00000923461, ENST00000923462, ENST00000923463, ENST00000923464, ENST00000923465, ENST00000923466, ENST00000923467, ENST00000923468, ENST00000923469, ENST00000923470, ENST00000923471, ENST00000923472, ENST00000923473, ENST00000923474, ENST00000923475, ENST00000923476, ENST00000923477, ENST00000923478, ENST00000923479, ENST00000923480, ENST00000923481, ENST00000923482, ENST00000923483, ENST00000964720, ENST00000992495, ENST00001024951, ENST00001024952, ENST00001024953, ENST00001024954, ENST00001024962, ENST00001073360, ENST00001073361, ENST00001073362, ENST00001073363, ENST00001073366, ENST00001073368, ENST00001073371, ENST00001073381, ENST00001073383, ENST00001073385, ENST00001073387, ENST00001073407, ENST00001073417, ENST00001073418, ENST00001073420, ENST00001073424, ENST00001073425, ENST00001104009, ENST00001104010, ENST00001104011, ENST00001104012, ENST00001128472, ENST00001128473, ENST00001136740

RefSeq mRNA: 7 — MANE Select: NM_002520 NM_001037738, NM_001355006, NM_001355007, NM_001355009, NM_001355010, NM_002520, NM_199185

CCDS: CCDS43399, CCDS4376, CCDS4377, CCDS93824

Canonical transcript exons

ENST00000296930 — 11 exons

Exon	Start	End
ENSE00001026390	171405302	171405403
ENSE00001026397	171407700	171407774
ENSE00001084445	171400153	171400210
ENSE00001084451	171400839	171400925
ENSE00001084453	171392914	171392978
ENSE00001084454	171392710	171392816
ENSE00003517265	171390051	171390130
ENSE00003536019	171391305	171391424
ENSE00003625205	171391706	171391799
ENSE00003906984	171387849	171388006
ENSE00003909747	171410527	171410900

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 326.0238 / max 6404.1810, expressed in 1828 samples.

Highest expression (Bgee): calcaneal tendon, ovary, ventricular zone, endocervix, body of uterus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NPM1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.3e-10	-0.24	5:171388517:C:T
Muscle Skeletal	eqtl	4.3e-05	+0.12	5:171376454:G:A
Heart Atrial Appendage	eqtl	8.1e-04	+0.12	5:171387019:C:T
Cells Cultured fibroblasts	sqtl	2.1e-03	+0.15	5:171421120:G:A
Heart Left Ventricle	eqtl	2.8e-03	-0.47	5:170540723:T:C
Esophagus Muscularis	eqtl	2.3e-02	-0.21	5:172047170:G:A
Adipose Visceral Omentum	eqtl	3.0e-02	-0.23	5:172234535:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-02	+0.28	5:171842760:A:G
Skin Not Sun Exposed Suprapubic	eqtl	3.7e-02	-0.31	5:171462091:C:T
Nerve Tibial	eqtl	3.7e-02	-0.26	5:171358546:T:C
Minor Salivary Gland	eqtl	4.5e-02	-0.43	5:171538367:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
60178	326.0238	1828

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.78	gold quality
left ovary	UBERON:0002119	99.70	gold quality
ventricular zone	UBERON:0003053	99.67	gold quality
right ovary	UBERON:0002118	99.66	gold quality
endocervix	UBERON:0000458	99.64	gold quality
body of uterus	UBERON:0009853	99.63	gold quality
ganglionic eminence	UBERON:0004023	99.62	gold quality
body of pancreas	UBERON:0001150	99.61	gold quality
right uterine tube	UBERON:0001302	99.56	gold quality
right testis	UBERON:0004534	99.56	gold quality
ectocervix	UBERON:0012249	99.56	gold quality
left testis	UBERON:0004533	99.54	gold quality
cortical plate	UBERON:0005343	99.53	gold quality
adrenal tissue	UBERON:0018303	99.52	gold quality
colonic epithelium	UBERON:0000397	99.51	gold quality
mucosa of stomach	UBERON:0001199	99.50	gold quality
left uterine tube	UBERON:0001303	99.50	gold quality
gall bladder	UBERON:0002110	99.49	gold quality
metanephros cortex	UBERON:0010533	99.49	gold quality
stromal cell of endometrium	CL:0002255	99.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.48	gold quality
body of stomach	UBERON:0001161	99.47	gold quality
popliteal artery	UBERON:0002250	99.47	gold quality
tibial artery	UBERON:0007610	99.47	gold quality
left lobe of thyroid gland	UBERON:0001120	99.46	gold quality
islet of Langerhans	UBERON:0000006	99.45	gold quality
rectum	UBERON:0001052	99.44	gold quality
right lung	UBERON:0002167	99.43	gold quality
adenohypophysis	UBERON:0002196	99.43	gold quality
descending thoracic aorta	UBERON:0002345	99.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.42	gold quality
right lobe of thyroid gland	UBERON:0001119	99.41	gold quality
right coronary artery	UBERON:0001625	99.41	gold quality
left coronary artery	UBERON:0001626	99.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.41	gold quality
left adrenal gland	UBERON:0001234	99.40	gold quality
minor salivary gland	UBERON:0001830	99.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.39	gold quality
esophagus mucosa	UBERON:0002469	99.39	gold quality
left adrenal gland cortex	UBERON:0035825	99.39	gold quality
right adrenal gland cortex	UBERON:0035827	99.39	gold quality
right adrenal gland	UBERON:0001233	99.38	gold quality
pancreas	UBERON:0001264	99.37	gold quality
tibial nerve	UBERON:0001323	99.37	gold quality
skin of abdomen	UBERON:0001416	99.37	gold quality
lower esophagus	UBERON:0013473	99.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.37	gold quality
lower esophagus mucosa	UBERON:0035834	99.37	gold quality
esophagus	UBERON:0001043	99.36	gold quality
omental fat pad	UBERON:0010414	99.36	gold quality
peritoneum	UBERON:0002358	99.35	gold quality
upper lobe of left lung	UBERON:0008952	99.35	gold quality
aorta	UBERON:0000947	99.34	gold quality
ascending aorta	UBERON:0001496	99.33	gold quality
thoracic aorta	UBERON:0001515	99.33	gold quality
transverse colon	UBERON:0001157	99.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.31	gold quality
skin of leg	UBERON:0001511	99.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.24	gold quality
monocyte	CL:0000576	99.16	gold quality
thyroid gland	UBERON:0002046	99.15	gold quality
mucosa of transverse colon	UBERON:0004991	99.15	gold quality
granulocyte	CL:0000094	99.14	gold quality
leukocyte	CL:0000738	99.12	gold quality
saliva-secreting gland	UBERON:0001044	99.12	gold quality
cerebellar hemisphere	UBERON:0002245	99.12	gold quality
mononuclear cell	CL:0000842	99.10	gold quality
ovary	UBERON:0000992	99.10	gold quality
stomach	UBERON:0000945	99.06	gold quality
mouth mucosa	UBERON:0003729	99.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.05	gold quality
cerebellar cortex	UBERON:0002129	99.04	gold quality
right atrium auricular region	UBERON:0006631	99.03	gold quality
tongue squamous epithelium	UBERON:0006919	99.03	gold quality
pancreatic ductal cell	CL:0002079	99.01	gold quality
upper lobe of lung	UBERON:0008948	98.95	gold quality
coronary artery	UBERON:0001621	98.90	gold quality
hair follicle	UBERON:0002073	98.86	gold quality
gastrocnemius	UBERON:0001388	98.84	gold quality
pituitary gland	UBERON:0000007	98.81	gold quality
anterior cingulate cortex	UBERON:0009835	98.79	gold quality
testis	UBERON:0000473	98.77	gold quality
parotid gland	UBERON:0001831	98.77	gold quality
adrenal gland	UBERON:0002369	98.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.76	gold quality
vermiform appendix	UBERON:0001154	98.75	gold quality
smooth muscle tissue	UBERON:0001135	98.74	gold quality
right frontal lobe	UBERON:0002810	98.73	gold quality
cingulate cortex	UBERON:0003027	98.71	gold quality
cervix squamous epithelium	UBERON:0006922	98.70	gold quality
muscle of leg	UBERON:0001383	98.68	gold quality
spleen	UBERON:0002106	98.65	gold quality
tonsil	UBERON:0002372	98.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.62	gold quality
embryo	UBERON:0000922	98.60	gold quality
small intestine	UBERON:0002108	98.57	gold quality
colon	UBERON:0001155	98.56	gold quality
apex of heart	UBERON:0002098	98.52	gold quality
adrenal cortex	UBERON:0001235	98.51	gold quality
right lobe of liver	UBERON:0001114	98.49	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	3577.33
E-CURD-112	yes	3454.76
E-CURD-98	yes	3444.88
E-HCAD-4	yes	2629.11
E-MTAB-9801	yes	2281.16
E-HCAD-1	yes	2238.93
E-CURD-122	yes	1775.80
E-GEOD-125970	yes	1218.02
E-MTAB-9467	yes	69.98
E-MTAB-9221	yes	54.02
E-CURD-88	yes	35.89
E-CURD-46	yes	35.00
E-GEOD-134144	yes	31.27
E-HCAD-13	yes	28.22
E-MTAB-9067	yes	22.16

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	1213.0	high
Bone marrow	tissue	743.5	high
Lymph node	tissue	725.3	high
Tonsil	tissue	712.7	high
Thymus	tissue	636.5
Endometrium 1	tissue	614.4	high
Breast	tissue	557.7	high
Fallopian tube	tissue	499.7	high
Urinary bladder	tissue	490.3	high
Vagina	tissue	488.6	high
Thyroid gland	tissue	476.8	high
Pancreas	tissue	448.8	high
Appendix	tissue	441.4	high
Cervix	tissue	430.0	high
Smooth muscle	tissue	407.1	high
Epididymis	tissue	398.0	high
Placenta	tissue	397.8	high
Rectum	tissue	395.2	high
Esophagus	tissue	390.6	high
Kidney	tissue	350.0	high
Liver	tissue	345.8	high
Colon	tissue	332.9	high
Gallbladder	tissue	332.7	high
Duodenum	tissue	326.2	high
Prostate	tissue	318.2	high
Stomach 1	tissue	315.8	high
Adrenal gland	tissue	315.2	high
Heart muscle	tissue	315.1	high
Spleen	tissue	314.5	high
Salivary gland	tissue	312.2	high
Seminal vesicle	tissue	299.7	high
Small intestine	tissue	296.9	high
Adipose tissue	tissue	296.7	high
Skin 1	tissue	285.4	high
Pituitary gland	tissue	271.4
Skeletal muscle	tissue	271.1	high
Testis	tissue	265.9	high
Tongue	tissue	263.4
Parathyroid gland	tissue	261.2	high
Lung	tissue	240.5	high
Choroid plexus	tissue	179.8
Retina	tissue	149.1
Locus coeruleus	tissue	148.6
Nucleus accumbens	tissue	131.0
Spinal cord	tissue	127.3
Pons	tissue	123.9
Putamen	tissue	123.6
Superior colliculi	tissue	121.8
Hippocampus	tissue	118.7	high
Midbrain	tissue	118.0
Corpus callosum	tissue	117.2
Thalamus	tissue	116.2
Medulla oblongata	tissue	114.6
Septum	tissue	112.7
Hippocampal formation	tissue	112.2
Substantia nigra	tissue	109.9
Cerebellum	tissue	108.4	high
Postcentral gyrus	tissue	106.5
Hypothalamus	tissue	106.1
Basal ganglia	tissue	105.8	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (501.6), Cervical spinal cord, ventral horn (221.8), Supraoptic nucleus (214.3), Medial olivary nucleus (202.6), Anterior funiculus (white matter) (198.3).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets:

Target	Regulation
ATF5	Repression
BRD4	Unknown
CCND1	Unknown
CDKN1A	Activation
DNMT1	Unknown
ELF4	Unknown
FBP1	Repression
HOXA9	Repression
PTPN6	Activation
RPL3	Unknown
TAF1A	Activation
USP7	Unknown

Upstream regulators (CollecTRI, top): AP1, ATF5, CEBPB, CTNNB1, ELF4, GLI1, HIF1A, JUN, JUNB, MYC, RARA, STAT5A, TFAP2A, TP53, TXK, YY1

miRNA regulators (miRDB)

Targeting NPM1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 52 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
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-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3153	99.55	67.59	2337

Functional genomics

gnomAD constraint: pLI 0.996, LOEUF 0.313, missense Z 1.4 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000296930 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:171,387,949–171,387,985	14 / 16.2	0.87	no
5:171,387,986–171,391,758	43 / 109.6	0.39	no
5:171,391,759–171,392,723	2 / 21.4	0.09	yes (p 2.7e-05)
5:171,392,724–171,400,854	91 / 94.0	0.97	no
5:171,400,855–171,410,562	47 / 106.5	0.44	no
DepMap (CRISPR cell-line fitness): dependent in 81.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KARPAS-299 (-3.065), OCI-AML3 (-2.59), DEL (-2.383), A-172 (-2.357), EW-7 (-2.353), 769-P (-2.314), TC-71 (-2.237), A549 (-2.209), NMC-G1 (-1.979), NB10 (-1.942), KYSE-450 (-1.933), LNCaP clone FGC (-1.894), YCUB-2 (-1.886), CAL-51 (-1.841), OS186 (-1.832).

Literature-anchored findings (GeneRIF, showing 40)

• overexpressed in acute myeloid leukemia while translocations associated with this gene are absent (PMID:12031912)
• marker of proliferation activity of human peripheral lymphocytes (PMID:12057857)
• NPM is a crucial regulator of p53 (PMID:12080348)
• involvement of NPM/B23 in the acute response of mammalian cells to environmental stress, such as UV rays (PMID:12374805)
• overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis. Fanconi anemia lymphoblasts expressed low levels of NPM, which correlated with high ground-state activation of PKR and hypersensitivity to apoptotic cues (PMID:12882984)
• These findings suggest that an NPM/MLF1 fusion is the primary molecular abnormality in t(3;5) MDS and AML with multilineage dysplasia, and that cases with NPM/MLF1 may be clinically distinct from other MDS-associated disease (PMID:14506644)
• unique B23 conformation in hepatoma (PMID:14519847)
• Src-kinases, particularly pp60(c-src), associate with and are activated by NPM-ALK expression in various cells, and in cell lines established from patients with large cell lymphoma (PMID:14563642)
• Results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23. (PMID:14636574)
• NPM/ALK-mediated induction of Bcl-XL (PMID:14656879)
• cleavage of B23 by granzyme b in intact vascular smooth muscle cells is dependent upon both cell type and phenotype (PMID:14730621)
• These data suggest that nucleophosmin is an early responder to DNA damage that prevents premature activation of p53. (PMID:15082766)
• nucleophosmin is an NF-kappaB co-activator for the induction of the human SOD2 gene (PMID:15087454)
• BRCA1-BARD1 catalyzes the polyubiquitination of nucleolar phosphoprotein nucleophosmin/B23 (PMID:15184379)
• identification of Ser-4 in B23 as a major physiological substrate of Polo-like kinase 1 (PMID:15190079)
• NPM inhibits hypoxia-induced p53 phosphorylation at Ser-15 and interacts with p53 in hypoxic cells; hypoxia-driven cancer progression may require increased expression of NPM to suppress p53 activation and maintain cell survival (PMID:15310764)
• Aloe-emodin caused increase in the amount of proform and fragment of nucleophosmin in cytoplasm may be one of the important events for aloe-emodin-induced H460 cell apoptosis pf mpm-small cell lung cancer. (PMID:15514966)
• c-Myc-mediated expression of NPM decreases during retinoic acid-induced differentiation of HL-60 cells. (PMID:15589822)
• a novel association of B23 and Gadd45a and implicate B23 as an important regulator in Gadd45a nuclear import. (PMID:15644315)
• Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy. (PMID:15659725)
• CDK2-BRCA1-NPM pathway coordinately functions in cell growth and tumor progression pathways. (PMID:15665273)
• NPM inhibits ARF’s p53-dependent activity by targeting it to nucleoli and impairing ARF-Mdm2 association. (PMID:15684379)
• The molecular signature of cytoplasmic NPM+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem-cell phenotype, suggesting that cytoplasmic NPM+ AML may derive from a multipotent hematopoietic progenitor. (PMID:15831697)
• base sequences are given for NPM1 mutated childhood AML patients; consistent deletion/insertion features are presented (PMID:15870172)
• polyamine depletion increased expression of the NPM gene and enhances NPM nuclear translocation and increased NPM interacts with and stabilizes p53, leading to inhibition of IEC-6 cell proliferation (PMID:15872011)
• NPM inhibits ionizing irradiation-induced p53 transactivation, and interacts with p53 in hematopoietic cells. (PMID:15964625)
• the NPM1 mutation is not necessarily an early event during leukemogenesis; the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate (PMID:15994285)
• Nucleophosmin (NPM) may be a Ran-Crm1 substrate that controls centrosome duplication. (PMID:16041368)
• results indicate that HCV core can recruit B23 and p300 to relieve the repression effect of YY1 on B23 promoter activity (PMID:16170350)
• Enforced expression of an NPM cytoplasmic mutant acutely attenuates p53-dependent and -independent functions of Arf tumor suppressor protein, and also affects endogenous NPM localization. (PMID:16205118)
• These findings indicate the involvement of nucleophosmin in the regulation of pre-mRNA processing, and its activity is controlled by CDK2-mediated phosphorylation on Thr(199). (PMID:16376875)
• FRGY2a and YB1 disassemble nucleoli by sequestering B23, which is associated with pre-ribosomes and other structurally important nucleolar components (PMID:16415342)
• both alterations are crucial for acute myeloid leukemia NPM mutant export from nucleus to cytoplasm; NPM leukemic mutants in turn recruit the wild-type NPM from nucleoli to nucleoplasm and cytoplasm (PMID:16455950)
• NPM1 mutations represent a common genetic abnormality in adult acute myeloid leukemia and appears to identify patients with improved response toward treatment. (PMID:16455956)
• The sensitive RQ-PCR assays for NPM1 mutations can now monitor and quantify MRD in AML patients with normal karyotype and NPM1 gene mutations. (PMID:16541144)
• results suggest that B23 plays an important role in the intracellular localization of the core protein and replication of Japanese encephalitis virus (PMID:16547420)
• NPM1 mutations may be also involved in the pathogenesis of myelodysplastic syndromes. (PMID:16678898)
• the functional integrity of the B23 core motif is required for stability, efficient nucleolar localization as well as ARF binding (PMID:16679321)
• constitutive expression of C/EBPbeta in ALK-positive anaplastic large cell lymphoma and its relationship to NPM-ALK (PMID:16709933)
• new exon-12 NPM mutations in acute myeloid leukemia (PMID:16720834)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	npm1a	ENSDARG00000014329
mus_musculus	Npm1	ENSMUSG00000057113
rattus_norvegicus	AABR07055527.1	ENSRNOG00000039997
drosophila_melanogaster	Nlp	FBGN0016685
drosophila_melanogaster	Nph	FBGN0039735

Paralogs (2): NPM3 (ENSG00000107833), NPM2 (ENSG00000158806)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:106184) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 60 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic lethality, complete penetrance	3
increased leukocyte cell number	2
increased granulocyte number	2
abnormal cell proliferation	2
enlarged spleen	2
decreased embryo size	2
increased mean corpuscular volume	2
increased hematopoietic stem cell number	2
increased spleen weight	2
abnormal common myeloid progenitor cell morphology	2
embryonic lethality during organogenesis, complete penetrance	2
increased monocyte cell number	1
abnormal thrombopoiesis	1
extramedullary hematopoiesis	1
increased bone marrow cell number	1
enlarged liver	1
abnormal eye development	1
anophthalmia	1
anemia	1
abnormal placenta development	1
absent vitelline blood vessels	1
embryonic growth arrest	1
increased B cell derived lymphoma incidence	1
premature death	1
abnormal brain morphology	1

+35 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RC37	97.8%	Diamond
Rhinella marina	Q1HTZ8	87.0%	Diamond
Aquarana catesbeiana	Q1HTZ9	87.0%	Diamond
Bos taurus	Q3T160	83.7%	Diamond
Xenopus laevis	P05221	81.8%	Diamond
Gallus gallus	P16039	66.9%	Diamond
Lytechinus pictus	P91753	47.5%	Diamond
Patiria pectinifera	Q9NLA3	44.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORA70J	snoRNA	109616973
FGF18	protein-coding	8817
MIR3912	ncRNA	100500831

Protein

Protein identifiers

Nucleophosmin — P06748 (reviewed: P06748)

Alternative names: Nucleolar phosphoprotein B23, Nucleolar protein NO38, Numatrin

All UniProt accessions (15): A0A0S2Z491, A0A0S2Z4G7, A0A140VJQ2, A0A7I2V2X9, A0A7I2V3G5, A0A7I2V3U2, A0A7I2V433, A0A7I2V4G8, A0A7I2V579, A0A7I2V5J8, A0A7I2V5S2, A0A7I2YQC0, E5RGW4, E5RI98, P06748

UniProt curated annotations — full annotation on UniProt →

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. In complex with MYC enhances the transcription of MYC target genes. May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1.

Subunit / interactions. Decamer formed by two pentameric rings associated in a head-to-head fashion. Disulfide-linked dimers under certain conditions. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with NSUN2 and SENP3. Interacts with the methylated form of RPS10. Interacts (via N-terminal domain) with APEX1; the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts with isoform 1 of NEK2. Interacts with ROCK2 and BRCA2. Interacts with RPGR. Interacts with CENPW. Interacts with EIF2AK2/PKR. Interacts with CEBPA (isoform 4). Interacts with DDX31; this interaction prevents interaction between NPM1 and HDM2. Interacts with MYC; competitive with NOP53. Interacts with NOP53; the interaction is direct and competitive with MYC. Interacts with LRRC34. Interacts with RRP1B. Interacts with NPM3. Interacts with ALKBH2. Interacts with TTF1 (via C-terminal region). Interacts with NOP2. Interacts with ARID3C (via REKLES DOMAIN); the interaction mediates ARID3C nuclear shuttling. Interacts with RSMC. (Microbial infection) Interacts with hepatitis delta virus S-HDAg. (Microbial infection) Interacts with HTLV1 Rex protein (via N-terminal nuclear localization signal).

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Acetylated at C-terminal lysine residues, thereby increasing affinity to histones. ADP-ribosylated. Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 by PLK2 in S phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at Ser-4 by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 and Thr-199. Phosphorylation at Thr-199 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-199, Thr-219, Thr-234 and Thr-237 during cell mitosis. When these four sites are phosphorylated, RNA-binding activity seem to be abolished. May be phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when complexed to Kaposi’s sarcoma herpesvirus (KSHV) V-cyclin, leading to viral reactivation by reducing viral LANA levels. Sumoylated by ARF. Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36.

Disease relevance. 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. A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. 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.

Similarity. Belongs to the nucleoplasmin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P06748-1	1	yes
P06748-2	2
P06748-3	3

RefSeq proteins (7): NP_001032827, NP_001341935, NP_001341936, NP_001341938, NP_001341939, NP_002511, NP_954654 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004301	Nucleoplasmin	Family
IPR024057	Nucleoplasmin_core_dom	Domain
IPR032569	NPM1_C	Domain
IPR036824	Nucleoplasmin_core_dom_sf	Homologous_superfamily

Pfam: PF03066, PF16276

UniProt features (118 total): modified residue 36, sequence conflict 17, cross-link 17, mutagenesis site 17, strand 8, region of interest 5, compositionally biased region 5, helix 4, site 3, short sequence motif 2, splice variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
7OBG	Crystal structure of 14-3-3 sigma in complex with NPM1 phosphopeptide	X-RAY DIFFRACTION	1.8
7OBH	Crystal structure of 14-3-3 sigma in complex with NPM1 phosphopeptide and stabilizer …	X-RAY DIFFRACTION	2
5EHD	Crystal structure of human nucleophosmin-core in complex with cytochrome c	X-RAY DIFFRACTION	2.55
2P1B	Crystal structure of human nucleophosmin-core	X-RAY DIFFRACTION	2.75
8AH2	Crystal structure of human 14-3-3 zeta fused to the NPM1 peptide including …	X-RAY DIFFRACTION	2.9
8AS5	CryoEM structure of the human Nucleophosmin 1 core	ELECTRON MICROSCOPY	3.53
2LLH	NMR structure of Npm1_c70	SOLUTION NMR
2VXD	The structure of the C-terminal domain of Nucleophosmin	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06748-F1	73.42	0.38

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, Human disease related genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli rim; nucleoplasm

Antibody reliability (HPA): IH supported · IF enhanced

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 (3)

Position	Role
55	interaction between pentamers
80	interaction between pentamers
175–176	breakpoint for translocation to form npm1-mlf1

Post-translational modifications (53)

Type	Positions
Phosphoserine	254, 4, 10, 43, 70, 125, 137, 139, 227, 242, 243, 254, 260
N6-acetyllysine	257, 32, 150, 154, 212, 229, 230, 250, 257, 267, 273, 292
N-acetylmethionine	1
Phosphotyrosine	67
Phosphothreonine	75, 95, 199, 219, 234, 237, 279
Adp-ribosylserine	207
N6-succinyllysine	267
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	27, 32, 141, 150, 215, 248, 250, 257, 263, 267, 273
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	32, 248, 257, 267
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	230, 263

Mutagenesis-validated functional residues (17)

Position	Phenotype
4	abolishes phosphorylation by plk2 and impairs centriole duplication.
4	mimicks phosphorylation state, inducing accumulation of centrioles.
95	does not affect phosphorylation by plk2.
125	does not affect phosphorylation by plk2.
199	partial loss of phosphorylation. does not affect phosphorylation by plk2.
219	partial loss of phosphorylation.
234	partial loss of phosphorylation; when associated with a-237.
237	partial loss of phosphorylation.
248	partial destabilization of the structure.
250	increase in the stabilization of the structure.
263	increase in the stabilization of the structure and partial delocalization to the nucleoplasm. complete delocalization to the nucleoplasm …
263	no change in the sumoylation level.
267	increase in the stabilization of the structure and complete delocalization to the nucleoplasm. complete delocalization to the nucleoplasm …
268	complete destabilization of the structure and loss of nucleolus localization; when associated with a-276.
276	complete destabilization of the structure and loss of nucleolus localization; when associated with a-268.
288	complete destabilization of the structure; when associated with a-290.
290	partial destabilization of the structure. complete destabilization of the structure; when associated with a-288.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 37; 15 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

37 pathways:

ID	Pathway	Evidence
R-HSA-9700645	ALK mutants bind TKIs ⚕	curated
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer ⚕	curated
R-HSA-9692914	SARS-CoV-1-host interactions ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere	curated
R-HSA-9833482	PKR-mediated signaling	curated
R-HSA-3899300	SUMOylation of transcription cofactors	curated
R-HSA-8869496	TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation	curated
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-177243	Interactions of Rev with host cellular proteins ⚕	—
R-HSA-180746	Nuclear import of Rev protein ⚕	electronic
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes	—
R-HSA-1640170	Cell Cycle	—
R-HSA-73886	Chromosome Maintenance	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-168256	Immune System	—
R-HSA-913531	Interferon Signaling	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-774815	Nucleosome assembly	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (33): ribosomal large subunit export from nucleus (GO:0000055), ribosomal small subunit export from nucleus (GO:0000056), DNA repair (GO:0006281), nucleosome assembly (GO:0006334), chromatin remodeling (GO:0006338), protein import into nucleus (GO:0006606), intracellular protein transport (GO:0006886), nucleocytoplasmic transport (GO:0006913), centrosome cycle (GO:0007098), signal transduction (GO:0007165), canonical NF-kappaB signal transduction (GO:0007249), intracellular protein localization (GO:0008104), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), regulation of centrosome duplication (GO:0010824), negative regulation of centrosome duplication (GO:0010826), macrophage differentiation (GO:0030225), cellular response to UV (GO:0034644), ribosome assembly (GO:0042255), ribosomal large subunit biogenesis (GO:0042273), ribosomal small subunit biogenesis (GO:0042274), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of centriole replication (GO:0046599), cellular senescence (GO:0090398), regulation of mRNA stability involved in cellular response to UV (GO:1902629), positive regulation of cell cycle G2/M phase transition (GO:1902751), positive regulation of protein localization to nucleolus (GO:1904751), positive regulation of cytoplasmic translation (GO:2000767), positive regulation of macromolecule metabolic process (GO:0010604), regulation of cell population proliferation (GO:0042127), ribosome biogenesis (GO:0042254)

GO Molecular Function (18): core promoter sequence-specific DNA binding (GO:0001046), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), protein kinase inhibitor activity (GO:0004860), rRNA binding (GO:0019843), protein kinase binding (GO:0019901), Tat protein binding (GO:0030957), histone binding (GO:0042393), protein homodimerization activity (GO:0042803), ribosomal large subunit binding (GO:0043023), ribosomal small subunit binding (GO:0043024), NF-kappaB binding (GO:0051059), molecular adaptor activity (GO:0060090), DNA-binding transcription factor binding (GO:0140297), nucleic acid binding (GO:0003676), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (16): granular component (GO:0001652), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), focal adhesion (GO:0005925), large ribosomal subunit (GO:0015934), small ribosomal subunit (GO:0015935), membrane (GO:0016020), nuclear speck (GO:0016607), spindle pole centrosome (GO:0031616), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

16 top-level categories:

Category	Pathways
Signaling by ALK in cancer	2
Interactions of Rev with host cellular proteins	1
SUMO E3 ligases SUMOylate target proteins	1
Nucleosome assembly	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
SARS-CoV-1 Infection	1
Signaling by ALK fusions and activated point mutants	1
Antimicrobial mechanism of IFN-stimulated genes	1
Interferon Signaling	1
Immune System	1
Viral Infection Pathways	1
HIV Infection	1
Host Interactions of HIV factors	1
RNA Polymerase II Transcription	1
Post-translational protein modification	1

GO top-level categories

showing 60 of 71 GO namespaces:

Category	Terms
cellular anatomical structure	5
binding	4
ribosomal subunit export from nucleus	2
chromatin organization	2
cell population proliferation	2
regulation of cell population proliferation	2
centrosome duplication	2
ribosome biogenesis	2
RNA polymerase II-specific DNA-binding transcription factor binding	2
protein binding	2
ribosome binding	2
nuclear lumen	2
ribosomal subunit	2
protein-containing complex	2
DNA metabolic process	1
DNA damage response	1
nucleosome organization	1
protein-DNA complex assembly	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
nuclear transport	1
cell cycle process	1
microtubule organizing center organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
macromolecule localization	1
positive regulation of cellular process	1
negative regulation of cellular process	1
regulation of centrosome cycle	1
regulation of centrosome duplication	1
negative regulation of centrosome cycle	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
response to UV	1
cellular response to light stimulus	1
membraneless organelle assembly	1
ribonucleoprotein complex biogenesis	1
transcription cis-regulatory region binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
RNA binding	1
kinase binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
transcription factor binding	1
nucleolus	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 45 of 68 annotations. The rest are phylogenetic / computational / electronic (IEA).

45 experimentally-supported GO terms:

GO term	NS	Evidence
DNA repair	BP	direct assay
canonical NF-kappaB signal transduction	BP	mutant phenotype
cellular response to UV	BP	direct assay
cellular senescence	BP	mutant phenotype
centrosome cycle	BP	mutant phenotype
intracellular protein localization	BP	direct assay
macrophage differentiation	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
negative regulation of cell population proliferation	BP	mutant phenotype
negative regulation of centrosome duplication	BP	mutant phenotype
nucleocytoplasmic transport	BP	direct assay
nucleosome assembly	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of cell cycle G2/M phase transition	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of cytoplasmic translation	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
protein import into nucleus	BP	direct assay
regulation of centriole replication	BP	mutant phenotype
regulation of mRNA stability involved in cellular response to UV	BP	mutant phenotype
centrosome	CC	direct assay
cytoplasm	CC	direct assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-DNA complex	CC	direct assay
protein-containing complex	CC	direct assay
ribonucleoprotein complex	CC	direct assay
spindle pole centrosome	CC	direct assay
DNA-binding transcription factor binding	MF	physical interaction
NF-kappaB binding	MF	direct assay
RNA binding	MF	direct assay
Tat protein binding	MF	direct assay
core promoter sequence-specific DNA binding	MF	direct assay
histone binding	MF	direct assay
molecular adaptor activity	MF	direct assay
protein homodimerization activity	MF	direct assay
protein kinase binding	MF	physical interaction
protein kinase inhibitor activity	MF	direct assay
rRNA binding	MF	physical interaction
ribosomal large subunit binding	MF	direct assay
ribosomal small subunit binding	MF	direct assay
transcription coactivator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 5,060 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPM1	FLT3	P36888	930
NPM1	ALK	Q9UM73	866
NPM1	NUCLEOLIN	P19338	860
NPM1	ASXL1	Q8IXJ9	857
NPM1	CEBPA	P49715	856
NPM1	RARA	P10276	851
NPM1	TET2	Q6N021	832
NPM1	FBL	P22087	807
NPM1	NUMA1	Q14980	799
NPM1	DNMT3A	Q9Y6K1	791
NPM1	IDH1	O75874	780
NPM1	IDH2	P48735	777
NPM1	RUNX1	Q01196	776
NPM1	SURF6	O75683	768
NPM1	CD34	P28906	759

IntAct

Human interaction partners of NPM1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 154 partners by confidence:

Partner	Interaction type	MIscore	Records
PINX1	physical association	0.810	9
SENP3	physical association	0.780	5
NPM2	physical association	0.740	12
AURKB	phosphorylation reaction	0.710	5
RRP1B	association	0.710	5
BOP1	colocalization	0.710	1
MYBBP1A	colocalization	0.710	1
USP7	physical association	0.700	5
MDM2	physical association	0.700	4
TP53	physical association	0.680	6
LARP4	physical association	0.670	1
PELP1	colocalization	0.660	3
CCDC124	colocalization	0.650	6
RPS6	physical association	0.650	1
EIF3E	physical association	0.640	1
L2	association	0.620	8
NP	colocalization	0.620	4
MPHOSPH10	association	0.610	1
NCL	proximity	0.610	1
NVL	association	0.610	1
HEMGN	physical association	0.600	7
NIBAN1	physical association	0.600	7
CENPA	association	0.600	4
EIF2AK2	physical association	0.600	3
TFAP2A	physical association	0.590	6
KPNA3	direct interaction	0.590	1
TERT	association	0.580	5
M	physical association	0.580	3
KPNA4	direct interaction	0.570	1
COX8A	physical association	0.560	3

BioGRID (2,150 interactions; top human partners by supporting records in a sample of 600 records): DNAJB4 (Affinity Capture-Western; 6 records), EIF2AK2 (Affinity Capture-Western; 5 records), NPM3 (Affinity Capture-MS; 5 records), CACYBP (Affinity Capture-MS; 4 records), CD24 (Affinity Capture-MS; 4 records), GNL3 (Affinity Capture-MS; 4 records), NPM2 (Two-hybrid; 4 records), TP53 (Affinity Capture-Western; 4 records), BRCA2 (Affinity Capture-MS; 3 records), C3orf17 (Affinity Capture-MS; 3 records), CDKN2A (Reconstituted Complex; 3 records), DDX24 (Affinity Capture-MS; 3 records), GNL2 (Affinity Capture-MS; 3 records), GTPBP4 (Affinity Capture-MS; 3 records), HIST1H1B (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 21 of 32 signaling interactions:

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	NPM1	phosphorylation
PLK1	up-regulates	NPM1	phosphorylation
PLK2	up-regulates	NPM1	phosphorylation
CDK1	unknown	NPM1	phosphorylation
CDK2	unknown	NPM1	phosphorylation
CyclinE/CDK2	“down-regulates activity”	NPM1	phosphorylation
CyclinB/CDK1	“down-regulates activity”	NPM1	phosphorylation
CDKN2A	“down-regulates quantity by destabilization”	NPM1	binding
NPM1	“down-regulates activity”	HEXIM1	binding
NPM1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
NPM1	“up-regulates activity”	CENPA	binding
NPM1	“down-regulates quantity by repression”	FBP1	“transcriptional regulation”
RNF144B	“down-regulates quantity by destabilization”	NPM1	ubiquitination
USP36	“up-regulates quantity by stabilization”	NPM1	deubiquitination
AKT1	“down-regulates activity”	NPM1	phosphorylation
DUSP3	“down-regulates activity”	NPM1	dephosphorylation
CHUK	“up-regulates activity”	NPM1	phosphorylation
ATM	“up-regulates activity”	NPM1	phosphorylation
CDK2	“down-regulates activity”	NPM1	phosphorylation
NPM1	“up-regulates activity”	CDKN2A	binding
NPM1	“up-regulates quantity”	FBXW7	binding

Protein complexes (CORUM) (12)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

12 complexes by size:

Complex	Subunits	Members
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13
★ H2AX complex, without IR exposure	13	H2BC26, SSB, SSRP1, SUPT16H, CALM1, H4C1, HNRNPR, HSPA5, NPM1, PABPC1, CALR, EIF3L, H2AX
H2AX complex II	10	CALR, H2BC14, H2BC3, H4C1, PTCD3, YBX3, H2AX, H2BC26, HSPA5, NPM1
★ TLE1 corepressor complex	10	HSPA4, NCL, NPM1, RAD50, TOP2B, ACTB, MYH10, NONO, PARP1, TLE1
★ H2AX complex I, IR-induced	9	H4C1, NPM1, PARP1, YBX3, DHX30, H2BC26, HSPA5, CALR, H2AX
★ CTCF-PARP1-HIS-KPNA-LMNA-TOP complex	9	TOP2A, NPM1, CTCF, H2AC18, H2AZ1, KPNA1, KPNA3, LMNA, PARP1
★ TLE1 corepressor complex	8	NCL, NONO, NPM1, PARP1, RAD50, TLE1, TOP2B, HSPA4
★ BRCA2-NPM1-ROCK2 complex	3	BRCA2, NPM1, ROCK2
ARF-Mule complex	3	CDKN2A, HUWE1, NPM1
B23-NPM3 complex	2	NPM1, NPM3
CTCF-nucleophosmin complex	2	CTCF, NPM1
NPM1-PA2G4 complex	2	NPM1, PA2G4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
SUMOylation of transcription factors	5	26.2×	6e-04
Regulation of TP53 Activity through Acetylation	5	20.9×	6e-04
Regulation of TP53 Degradation	6	16.1×	6e-04
SARS-CoV-1 activates/modulates innate immune responses	5	12.5×	3e-03
SUMO E3 ligases SUMOylate target proteins	7	11.5×	6e-04
Influenza Infection	7	11.3×	6e-04
Negative regulation of NOTCH4 signaling	5	10.9×	4e-03
SUMOylation	7	10.5×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of signal transduction by p53 class mediator	5	13.4×	6e-03
rRNA processing	8	7.9×	3e-03
protein import into nucleus	7	7.0×	9e-03
regulation of protein stability	8	7.0×	4e-03
negative regulation of apoptotic process	15	3.6×	4e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

AML with mutated NPM1 is a provisional entity in the WHO classification of AML and is recommended to be tested in patients with cytogenetically normal AML (CN-AML). FLT3 mutations should be evaluated concurrently as they have prognostic consequences. NPM1 mutations are concentrated in exon 12, most frequently W288fs which results in cytoplasmic sequestration of the protein. Exon 12 NPM1 mutations in the absence of FLT3-ITD are associated with good prognostic outcomes. Mice expressing the Npm1-W288fs mutation develop myeloproliferative neoplasms but not overt leukemia, indicating it may require additional mutations to promote leukemic development.

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — HCC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for NPM1: 97 ClinVar records (8 pathogenic / likely pathogenic); 3 CIViC cancer variants; 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	0
Uncertain significance	25
Likely benign	13
Benign	16

Top pathogenic / likely-pathogenic (8)

Showing all 8 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
13998	NM_002520.7(NPM1):c.860_863dup (p.Trp288fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
632551	NM_002520.7(NPM1):c.869_875delinsCCCTGGCTAGG (p.Trp290fs)	Pathogenic	criteria provided, single submitter	1
14001	NM_002520.7(NPM1):c.863_864insCCTG (p.Trp288fs)	Pathogenic	no assertion criteria provided	2
13999	NM_002520.7(NPM1):c.863_864insCATG (p.Trp288fs)	Pathogenic	no assertion criteria provided	1
14000	NM_002520.7(NPM1):c.863_864insCGTG (p.Trp288fs)	Pathogenic	no assertion criteria provided	1
810668	NM_002520.7(NPM1):c.864_873delinsTTTAAGGATTCGTC (p.Trp288fs)	Pathogenic	no assertion criteria provided	1
1701937	NM_002520.7(NPM1):c.885A>G (p.Ter295=)	Pathogenic	no assertion criteria provided	1
1701958	NM_002520.7(NPM1):c.875del (p.Lys292fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore NPM1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

1,138 missense substitutions predicted likely pathogenic (of 1,966 scored), across 238 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M251	9	0.885	0.999
H115	8	0.995	0.999
F268	8	0.995	1.000
H40	8	0.993	0.998
F92	8	0.992	1.000
F19	8	0.986	1.000
F31	8	0.979	0.998
D55	8	0.968	0.999
F276	8	0.957	0.999
H58	8	0.949	0.997
S112	8	0.934	0.999
N274	8	0.890	0.997
N210	8	0.883	0.975
D3	8	0.845	0.976
N38	8	0.820	0.988
W288	7	0.997	1.000
W290	7	0.995	0.999
E93	7	0.990	0.999
C21	7	0.989	0.998
Q41	7	0.985	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.58e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.17e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.24e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000129
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000674
Lung Adenocarcinoma (TCGA)	unfavorable	0.000711

Disease associations

OMIM: gene MIM:164040 | disease phenotypes: MIM:601626

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
dyskeratosis congenita	Strong	Autosomal dominant	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
bone marrow failure syndrome	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
DDG2P	green
Paediatric disorders	green
Cytopenia - NOT Fanconi anaemia	amber
Cytopenias and congenital anaemias	amber

Mondo (3): acute myeloid leukemia (MONDO:0018874), acute myeloid leukemia with multilineage dysplasia (MONDO:0019456), dyskeratosis congenita (MONDO:0015780)

Orphanet (2): Acute myeloid leukemia (Orphanet:519), Acute myeloid leukaemia with myelodysplasia-related features (Orphanet:86845)

HPO phenotypes

showing 60 of 99 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000035	Abnormal testis morphology
HP:0000164	Abnormality of the dentition
HP:0000212	Gingival overgrowth
HP:0000225	Gingival bleeding
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000600	Abnormality of the pharynx
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000704	Periodontitis
HP:0000790	Hematuria
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
HP:0000967	Petechiae
HP:0000975	Hyperhidrosis
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0000982	Palmoplantar keratoderma
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches
HP:0001231	Abnormal fingernail morphology
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001442	Typified by somatic mosaicism
HP:0001511	Intrauterine growth retardation
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001874	Abnormality of neutrophils
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001928	Abnormality of coagulation
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002205	Recurrent respiratory infections
HP:0002216	Premature graying of hair
HP:0002240	Hepatomegaly
HP:0002321	Vertigo
HP:0002514	Cerebral calcification
HP:0002575	Tracheoesophageal fistula
HP:0002650	Scoliosis
HP:0002653	Bone pain
HP:0002664	Neoplasm

GWAS associations

4 associations:

Study	Trait	p-value
GCST010702_141	Subcortical volume (MOSTest)	9e-14
GCST010703_28	Brain morphology (MOSTest)	4e-11
GCST012334_7	Multisite chronic pain	3e-8
GCST008163_10	Height	3e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0010100	multisite chronic pain

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2111387 (CHIMERIC PROTEIN), CHEMBL4296165 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748220 (PROTEIN-PROTEIN INTERACTION), CHEMBL5178 (SINGLE PROTEIN)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes NPM1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

2 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
CERITINIB	NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor)	2	4
CRIZOTINIB	NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor)	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,316 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL1232461	MOLIBRESIB	2	1,601
CHEMBL3545360	ASP-3026	1	711

Clinical evidence (CIViC)

Drug × variant × indication, from 12 curated evidence items; also 17 prognostic, 10 diagnostic, 1 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

11 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
NPM1 EXON 11 MUTATION	Tretinoin	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID137 +1
NPM1 EXON 11 MUTATION	Ziftomenib	Acute Myeloid Leukemia With Mutated NPM1	Sensitivity/Response	CIViC B	EID13285
NPM1 EXON 11 MUTATION	Revumenib	Acute Myeloid Leukemia With Mutated NPM1	Sensitivity/Response	CIViC B	EID13286
NPM1 EXON 11 MUTATION	Daunorubicin	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID147
NPM1 EXON 11 MUTATION	Valproic Acid	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID148
NPM1 MUTATION	Revumenib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID12743
NPM1 EXON 11 MUTATION	NSC348884 + Tretinoin	Acute Myeloid Leukemia	Sensitivity/Response	CIViC D	EID149
NPM1 W288FS	NSC348884	Acute Myeloid Leukemia	Sensitivity/Response	CIViC D	EID152
NPM1 EXON 11 MUTATION	Anti-CD123 + Anti-CD33	Acute Myeloid Leukemia	Sensitivity/Response	CIViC E	EID150
NPM1 EXON 11 MUTATION	Anti-CD33	Acute Myeloid Leukemia	Sensitivity/Response	CIViC E	EID151
NPM1 W288FS	Daunorubicin + Cytarabine + Etoposide	Acute Myeloid Leukemia	Sensitivity/Response	CIViC E	EID153

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

1 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
NPM1 MUTATION	Acute Myeloid Leukemia With Mutated NPM1		Diagnostic	Tier I - Level A	Positive

CIViC curated variants (3)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

MUTATION, EXON 11 MUTATION (exon variant), W288FS (frameshift elongation).

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

43 measured of 51 human assays (55 total across all organisms); most potent 43 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-bromo-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	IC50	0.77 nM	US-20230322822: ARYL PHOSPHOROUS OXIDE COMPOUNDS AND USE THEREOF
CHEMBL1822521	IC50	3.8 nM
CHEMBL1822520	IC50	5 nM
CERITINIB	IC50	5 nM	US-10053458: Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient
CHEMBL4762861	IC50	5 nM
CHEMBL1822527	IC50	7 nM
CHEMBL4762256	IC50	8 nM
CHEMBL1822523	IC50	8.8 nM
CHEMBL1822519	IC50	9 nM
CHEMBL1822522	IC50	9 nM
CHEMBL1822524	IC50	9 nM
ASP-3026	IC50	10 nM
CHEMBL1822525	IC50	10 nM
CHEMBL1822526	IC50	15 nM
3-methyl-6-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-2H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	IC50	20 nM	US-8592432: Compounds and compositions as protein kinase inhibitors
5-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-7-N-(2-propan-2-ylsulfonylphenyl)-2H-triazolo[4,5-d]pyrimidine-5,7-diamine	IC50	48 nM	US-8592432: Compounds and compositions as protein kinase inhibitors
CHEMBL4739938	IC50	186 nM
CHEMBL4795530	IC50	212 nM
CHEMBL3734798	IC50	261 nM
5-benzo[1,3]dioxol-5-yl-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amide	IC50	400 nM
5-benzo[1,3]dioxol-5-yl-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amide	KI	500 nM
CHEMBL3115504	IC50	650 nM
5-benzo[1,3]dioxol-5-yl-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid [4-(4-methyl-piperazin-1-yl)-phenyl]-amide	IC50	700 nM
3-(4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-phenol	IC50	870 nM
CHEMBL4749543	IC50	1080 nM
5-benzo[1,3]dioxol-5-yl-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid {4-[3-(4-methyl-piperazin-1-yl)-propyl]-phenyl}-amide	KI	1100 nM
CHEMBL4634073	IC50	1200 nM
CHEMBL4858720	IC50	1300 nM
CHEMBL5653589	KD	1440 nM
CHEMBL4791252	IC50	1910 nM
CHEMBL4762929	IC50	1930 nM
CHEMBL3589689	EC50	2500 nM
CHEMBL4747015	IC50	3170 nM
CHEMBL4798141	IC50	3300 nM
CHEMBL4755518	IC50	3450 nM
CHEMBL4780490	IC50	3880 nM
CHEMBL4756013	IC50	3930 nM
CHEMBL4779222	IC50	4600 nM
CHEMBL4640601	IC50	8300 nM
CHEMBL4854822	IC50	8500 nM
CHEMBL593574	EC50	9700 nM
CHEMBL3115497	IC50	10000 nM
CHEMBL3115496	IC50	69000 nM

ChEMBL bioactivities

82 potent at pChembl≥5 of 87 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.91	IC50	1.24	nM	CHEMBL6162078
8.70	IC50	2	nM	CRIZOTINIB
8.52	IC50	3	nM	CHEMBL4762256
8.22	IC50	6	nM	CHEMBL4762256
8.17	IC50	6.8	nM	ASP-3026
8.15	IC50	7	nM	CHEMBL4762861
8.08	Kd	8.259	nM	CHEMBL3752910
8.08	ED50	8.259	nM	CHEMBL3752910
8.00	IC50	10	nM	MOLIBRESIB
7.89	IC50	13	nM	CHEMBL4798141
7.70	IC50	20	nM	CHEMBL3651854
7.58	IC50	26	nM	CERITINIB
7.58	IC50	26	nM	CHEMBL3651854
7.52	IC50	30	nM	CHEMBL2158531
7.52	IC50	30	nM	CHEMBL3651854
7.48	IC50	33	nM	CHEMBL4791252
7.42	IC50	38	nM	CHEMBL4762861
7.40	IC50	40	nM	CHEMBL2158527
7.33	IC50	47	nM	CHEMBL3651885
7.33	IC50	47	nM	CHEMBL4779222
7.30	IC50	50	nM	CHEMBL1822527
7.29	IC50	51	nM	CRIZOTINIB
7.22	IC50	60	nM	CHEMBL2158525
7.22	IC50	60	nM	CHEMBL1822525
7.19	IC50	64	nM	CHEMBL3734798
7.16	IC50	70	nM	CHEMBL2158519
7.16	IC50	70	nM	CHEMBL2158518
7.16	IC50	70	nM	CHEMBL2158529
7.16	IC50	70	nM	CHEMBL2158526
7.16	IC50	70	nM	CHEMBL1822523
7.10	IC50	80	nM	CHEMBL2158516
7.10	IC50	80	nM	CHEMBL2158530
7.10	IC50	80	nM	CHEMBL1822521
7.10	IC50	80	nM	CHEMBL1822526
7.07	IC50	85	nM	CHEMBL1822522
7.00	IC50	100	nM	CHEMBL1934334
7.00	IC50	100	nM	CHEMBL2158511
7.00	IC50	100	nM	CHEMBL2158528
7.00	IC50	100	nM	CHEMBL1822519
7.00	IC50	100	nM	CHEMBL1822520
6.93	EC50	116.5	nM	CHEMBL4875115
6.82	IC50	150	nM	CHEMBL2158515
6.82	IC50	150	nM	CHEMBL2158586
6.82	IC50	150	nM	BOSUTINIB
6.82	IC50	150	nM	CHEMBL4755518
6.82	IC50	151	nM	CHEMBL3734798
6.70	IC50	200	nM	CHEMBL2158587
6.70	IC50	200	nM	CHEMBL2158521
6.70	IC50	200	nM	BOSUTINIB
6.70	IC50	200	nM	CHEMBL1822524

PubChem BioAssay actives

81 with measured affinity, of 285 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-bromo-4-N-(2-dimethylphosphoryl-4-methylphenyl)-2-N-[2-methoxy-5-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	2242670: Inhibition of N-terminal GST-fused human NPM1-ALK (1 to 680 residues) extracted from baculovirus expression system using Srctide as substrate incubated for 1 to 5 hrs in presence of ATP/Mg by Mobility shift assay	ic50	0.0012	uM
Crizotinib	2161822: Inhibition of human N-terminal GST-fused NPM1-ALK (1 to 680 residues) expressed in baculovirus expression system using Srctide as substrate measured after 1 hr by off-chip mobility shift assay relative to control	ic50	0.0020	uM
2-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1711502: Inhibition of NMP-ALK (unknown origin) expressed in human KARPAS-299 cells assessed as reduction in cell growth	ic50	0.0030	uM
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	2161822: Inhibition of human N-terminal GST-fused NPM1-ALK (1 to 680 residues) expressed in baculovirus expression system using Srctide as substrate measured after 1 hr by off-chip mobility shift assay relative to control	ic50	0.0068	uM
3-methyl-6-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)-2H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	1711502: Inhibition of NMP-ALK (unknown origin) expressed in human KARPAS-299 cells assessed as reduction in cell growth	ic50	0.0070	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148885: Binding affinity to human NPM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0083	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179037: Inhibition of NPM1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0100	uM
6-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0130	uM
3-methyl-6-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-2H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0200	uM
Ceritinib	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0260	uM
(2S)-3-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]propane-1,2-diol	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0300	uM
6-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0330	uM
N-[2-[2-(2-methoxy-4-piperidin-4-ylanilino)pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0400	uM
2-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0470	uM
5-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-7-N-(2-propan-2-ylsulfonylphenyl)-2H-triazolo[4,5-d]pyrimidine-5,7-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.0470	uM
N-[2-[2-[2-methoxy-4-(4-morpholin-4-ylpiperidin-1-yl)anilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0500	uM
N-[2-[2-[4-[4-[(2S)-2-hydroxypropyl]piperazin-1-yl]-2-methoxyanilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0600	uM
N-[2-[2-[4-[1-(2-hydroxyethyl)piperidin-4-yl]-2-methoxyanilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0600	uM
3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-3-yl)pyridin-2-amine	1711502: Inhibition of NMP-ALK (unknown origin) expressed in human KARPAS-299 cells assessed as reduction in cell growth	ic50	0.0640	uM
N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperazin-1-yl]phenyl]-7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0700	uM
N-[2-[2-[4-[1-[(2R)-2-hydroxypropyl]piperidin-4-yl]-2-methoxyanilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0700	uM
N-[2-methoxy-4-(1-methylpiperidin-4-yl)phenyl]-7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0700	uM
2-[4-[3-methoxy-4-[[5-methyl-7-[2-[methyl(methylsulfonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0700	uM
2-[4-[4-[[5-chloro-7-[2-[methyl(methylsulfonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]-3-methoxyphenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0700	uM
(2R)-1-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperazin-1-yl]propan-2-ol	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0800	uM
N-[2-[2-[4-[4-[(2R)-2-hydroxypropyl]piperazin-1-yl]-2-methoxyanilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0800	uM
1-fluoro-3-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]propan-2-ol	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0800	uM
2-[4-[3-methoxy-4-[[7-[2-[methyl(methylsulfonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.0800	uM
N-[2-methoxy-4-(4-morpholin-4-ylpiperazin-1-yl)phenyl]-7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.0850	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.1000	uM
(2S)-1-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperazin-1-yl]propan-2-ol	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.1000	uM
(2R)-1-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]propan-2-ol	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.1000	uM
2-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]-N-methylacetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.1000	uM
2-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.1000	uM
8-[4-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetyl]piperazin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1847263: Protac activity at CRBN/NPM-ALK in human KARPAS-299 cells assessed as induction of NPM-ALK fusion protein degradation incubated for 48 hrs by Western blot analysis	ec50	0.1165	uM
6-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4,6-triamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	0.1500	uM
Bosutinib	271009: Inhibition of NPM/ALK L256T mutant kinase activity in BaF3 cells by radioenzymatic assay	ic50	0.1500	uM
2-amino-1-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]-2-methylpropan-1-one	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.1500	uM
2-[4-[3-methoxy-4-[[7-(3-methoxy-4-pyridinyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.1500	uM
azetidin-2-yl-[4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]methanone	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.2000	uM
N-[2-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	617856: Inhibition of NPM/ALK phosphorylation in human KARPAS299 cells by ELISA	ic50	0.2000	uM
N-[2-[2-[5-fluoro-4-[4-[(2S)-2-hydroxypropyl]piperazin-1-yl]-2-methoxyanilino]pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl]-N-methylmethanesulfonamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.2000	uM
2-[4-[4-[[7-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]-3-methoxyphenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.2500	uM
6-methyl-2-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1711502: Inhibition of NMP-ALK (unknown origin) expressed in human KARPAS-299 cells assessed as reduction in cell growth	ic50	0.3280	uM
4,7-bis[4-(4-methylpiperazin-1-yl)phenyl]pyrazino[1,2-a]benzimidazole	1070241: Inhibition of NPM/ALK (unknown origin) transfected in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by [3H]-thymidine incorporation assay	ic50	0.3400	uM
3-[4-amino-7-[3-(hydroxymethyl)cyclobutyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	1774882: Inhibition of NPM-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 48 hrs by cell proliferation assay	ic50	0.3700	uM
2-[4-[4-[[7-(2,4-dimethoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]-3-methoxyphenyl]piperidin-1-yl]acetamide	694696: Inhibition of human NPM-ALK phosphorylation using 4-MeUP substrate by cell based assay	ic50	0.5000	uM
7-(4-methoxyphenyl)-4-[(E)-2-phenylethenyl]pyrazino[1,2-a]benzimidazole	1070241: Inhibition of NPM/ALK (unknown origin) transfected in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by [3H]-thymidine incorporation assay	ic50	0.8400	uM
3-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	1774882: Inhibition of NPM-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 48 hrs by cell proliferation assay	ic50	0.8700	uM
2-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)quinazoline-2,4-diamine	1711446: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay	ic50	1.0820	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects localization, decreases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression, affects binding, increases reaction	4
Arsenic Trioxide	increases expression, affects response to substance, decreases reaction, increases response to substance	3
Arsenic	affects methylation, increases expression, decreases expression, increases abundance	3
Tretinoin	affects binding, increases reaction, decreases expression	3
bisphenol S	affects localization, increases expression	2
Cisplatin	increases expression, decreases response to substance	2
Estradiol	decreases phosphorylation, increases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
UF010 compound	increases acetylation	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
hexamethylene bisacetamide	decreases expression	1
methylparaben	decreases expression, increases expression	1
afimoxifene	decreases expression	1
tetrabromobisphenol A	affects localization	1
manganese chloride	increases expression, increases abundance	1
cerous chloride	affects localization, decreases expression	1
lanthanum chloride	affects localization, decreases expression	1
coumarin	increases phosphorylation	1
triphenyltin	increases expression	1
cupric oxide	increases phosphorylation	1

ChEMBL screening assays

113 unique, capped per target: 108 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005525	Binding	Inhibition of NPM-ALK in human Karpas299 cells at 50 nM	Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. — *Proc Natl Acad Sci U S A*
CHEMBL861020	Functional	Antiproliferative activity against SUDHL1 expressing NPM-ALK by MTT assay	Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. — *J Med Chem*

Cellosaurus cell lines

30 cell lines: 30 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0538	SU-DHL-1	Cancer cell line	Male
CVCL_1170	DEL	Cancer cell line	Male
CVCL_1176	DMS 273	Cancer cell line	Female
CVCL_1324	Karpas-299	Cancer cell line	Male
CVCL_1711	SR	Cancer cell line	Male
CVCL_1844	OCI-AML-3	Cancer cell line	Male
CVCL_2093	Ki-JK	Cancer cell line	Male
CVCL_2098	L-82	Cancer cell line	Female
CVCL_2209	SUP-M2	Cancer cell line	Female
CVCL_5227	OCI-AML3/HaABCG2 clone 6.2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 319 trials:

NCT	Phase	Status	Title
NCT00199147	Phase 4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	Phase 4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	Phase 4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	Phase 4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	Phase 4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	Phase 4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	Phase 4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	Phase 4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	Phase 4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	Phase 4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	Phase 4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	Phase 4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	Phase 4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	Phase 4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	Phase 4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	Phase 4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	Phase 4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	Phase 4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	Phase 4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	Phase 4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	Phase 4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	Phase 4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	Phase 4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	Phase 4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	Phase 4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	Phase 4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	Phase 4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT07773909	Phase 4	COMPLETED	Venetoclax With Hypomethylating Agents in Newly Diagnosed AML Unfit for Intensive Chemotherapy
NCT00000589	Phase 3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	Phase 3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	Phase 3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	Phase 3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	Phase 3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	Phase 3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	Phase 3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	Phase 3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	Phase 3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	Phase 3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	Phase 3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	Phase 3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	Phase 3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia
NCT00266136	Phase 3	COMPLETED	Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)
NCT00317642	Phase 3	COMPLETED	A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)
NCT00322101	Phase 3	COMPLETED	Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00363025	Phase 3	TERMINATED	A Randomized Study of Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia.
NCT00406393	Phase 3	COMPLETED	Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402)
NCT00412360	Phase 3	COMPLETED	Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00428558	Phase 3	COMPLETED	Timed-Sequential Induction in CBF-AML
NCT00469144	Phase 3	COMPLETED	IV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome
NCT00474006	Phase 3	COMPLETED	High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML
NCT00476541	Phase 3	COMPLETED	NOPHO-AML 2004 Study for Children With Acute Myeloid Leukemia
NCT00480064	Phase 3	COMPLETED	Lomustine and Intermediate Dose Cytarabine in Older Patients With AML
NCT00495287	Phase 3	COMPLETED	A Remission Induction Therapy and Risk-oriented Postremission Strategy for Adult Acute Myelogenous Leukemia (AML)
NCT00513305	Phase 3	TERMINATED	Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia
NCT00568633	Phase 3	TERMINATED	Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
NCT00589082	Phase 3	COMPLETED	DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML
NCT00590837	Phase 3	COMPLETED	Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old
NCT00606723	Phase 3	COMPLETED	Allogenic Stem Cell Transplantation for Children, Adolescents and Young Adults With Relapsed or Refractory AML
NCT00656448	Phase 3	COMPLETED	A Randomized Trial of Procrit vs. No Procrit in AML and High Risk MDS
NCT00678275	Phase 3	COMPLETED	Chronic Graft-versus-host Disease (cGvHD) Prophylaxis With or Without ATG Prior to Stem Cell Transplantation (SCT) From HLA-identical Siblings in Patients With Acute Leukemia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NPM1 across ~30M SureChEMBL compounds — explore on Sugi Predict.