NEK2

Summary

NEK2 (NIMA related kinase 2, HGNC:7745) is a protein-coding gene on chromosome 1q32.3, encoding Serine/threonine-protein kinase Nek2 (P51955). Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells.

This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene.

Source: NCBI Gene 4751 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 67 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 280 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7745
Approved symbol	NEK2
Name	NIMA related kinase 2
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	NLK1, NEK2A, RP67, PPP1R111
Ensembl gene	ENSG00000117650
Ensembl biotype	protein_coding
OMIM	604043
Entrez	4751

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000366998, ENST00000366999, ENST00000462283, ENST00000489633, ENST00000540251, ENST00000908300

RefSeq mRNA: 3 — MANE Select: NM_002497 NM_001204182, NM_001204183, NM_002497

CCDS: CCDS1500, CCDS55682, CCDS73024

Canonical transcript exons

ENST00000366999 — 8 exons

Exon	Start	End
ENSE00001010393	211671202	211671284
ENSE00001010397	211670281	211670407
ENSE00001167194	211673483	211673723
ENSE00001443206	211662772	211663652
ENSE00001443207	211675384	211675621
ENSE00003674601	211667106	211667231
ENSE00003680198	211669113	211669332
ENSE00003720107	211674296	211674513

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 96.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9052 / max 66.4794, expressed in 1018 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17356	3.9052	1018

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.65	gold quality
ventricular zone	UBERON:0003053	96.54	gold quality
male germ cell	CL:0000015	95.07	gold quality
secondary oocyte	CL:0000655	91.75	gold quality
left testis	UBERON:0004533	90.60	gold quality
oocyte	CL:0000023	90.44	gold quality
right testis	UBERON:0004534	90.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.77	gold quality
testis	UBERON:0000473	89.58	gold quality
ganglionic eminence	UBERON:0004023	89.48	gold quality
embryo	UBERON:0000922	88.96	gold quality
adult organism	UBERON:0007023	88.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
bone marrow	UBERON:0002371	82.45	gold quality
trabecular bone tissue	UBERON:0002483	79.91	gold quality
rectum	UBERON:0001052	79.51	gold quality
mucosa of transverse colon	UBERON:0004991	78.82	gold quality
bone marrow cell	CL:0002092	76.18	gold quality
gingival epithelium	UBERON:0001949	75.72	silver quality
vermiform appendix	UBERON:0001154	75.56	gold quality
stromal cell of endometrium	CL:0002255	75.39	gold quality
thymus	UBERON:0002370	75.16	gold quality
amniotic fluid	UBERON:0000173	73.91	gold quality
esophagus squamous epithelium	UBERON:0006920	73.70	gold quality
duodenum	UBERON:0002114	73.54	gold quality
esophagus mucosa	UBERON:0002469	73.14	gold quality
gingiva	UBERON:0001828	73.01	silver quality
lower esophagus mucosa	UBERON:0035834	72.98	gold quality
caecum	UBERON:0001153	72.96	gold quality
bronchial epithelial cell	CL:0002328	72.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, FOXO1, GLI1, GLI2, TP53

miRNA regulators (miRDB)

45 targeting NEK2, 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-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-499A-3P	99.18	69.20	1392

Literature-anchored findings (GeneRIF, showing 40)

• Nek2.PP1C complex is regulated by Inh2 via inhibition of phosphatase activity to initiate centrosome separation (PMID:12221103)
• cell cycle-regulated serine phosphorylation of Hec1 by Nek2 is essential for faithful chromosome segregation (PMID:12386167)
• Nek2A function is required for the correct execution of mitosis (PMID:12857871)
• NEK2A is a kinetochore-associated protein kinase essential for faithful chromosome segregation (PMID:14978040)
• Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells (PMID:15161910)
• Nek2 is involved in activation of the G2 checkpoint and is not secondary to cell cycle arrest (PMID:15387139)
• Nek2 protein is significantly up-regulated in preinvasive in situ ductal carcinomas of the breast as well as in invasive breast carcinomas. (PMID:15492258)
• multiple processes involved in regulating the abundance of Nek2 kinase at the centrosome including microtubule binding, the centriolar satellite component pericentriolar material 1, and localized protein degradation (PMID:15659651)
• Down-regulation of NEK2A does not lead to mitotic defects; absence of the isozyme NK2B, a splice variant, leads to a mitotic delay and the formation of multinucleated cells. (PMID:15950749)
• summary of the expression, regulation and function of Nek2 and its roles in human cancer [review] (PMID:16084011)
• DNA damage-induced inhibition of Plk1 leads to inhibition of Nek2 activity and thus prevents centrosome separation (PMID:16157594)
• Mutational analysis of autophosphorylation sites identified by mass spectrometry and x-ray structure show a complex pattern of positive and negative regulatory effects on kinase activity correlated with effects on centrosomal splitting efficiency (PMID:17197699)
• Radiation-induced inhibition of centrosome splitting was abrogated in cells expressing Nek2 mutated in the PP1-binding motif outside the kinase domain. (PMID:17283141)
• Results report that NIP2, previously identified as centrobin, is a novel substrate of Nek2, and that NIP2 has a role in stabilizing the microtubule structure. (PMID:17535851)
• Results suggest that NEK2A-mediated phosphorylation of Sgo1 (SGOL1) provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores. (PMID:17621308)
• alternative splicing provides an unusual mechanism for modulating Nek2 localization, enabling it to have both nuclear and cytoplasmic functions. (PMID:17626005)
• Nek2 binds and phosphorylates beta-catenin. (PMID:18086858)
• that Hec1 binds to microtubule in low affinity and phosphorylation by NEK2A, which prevents aberrant kinetochore-microtubule connections in vivo, increases the affinity of the Ndc80 complex for microtubules in vitro (PMID:18297113)
• Nek2 plays a critical role in carcinogenesis, tumor invasion, and tumorigenic growth of breast carcinoma. (PMID:19038001)
• NEK2 overexpression is associated with papillary renal cell tumors with chromosome 1q duplication. (PMID:19123481)
• Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced centrosome amplification. (PMID:20581865)
• these results suggest that kendrin anchors Nek2A and suppresses its kinase activity at the centrosomes, and thus, is involved in the mechanism to prevent premature centrosome splitting during interphase. (PMID:20599736)
• Data show that although NEK2 was not universally recognized, it may serve as a tumor antigen for some patients. (PMID:20718755)
• Study reports that two Hippo pathway components, Mst2 and the scaffold protein Salvador (hSav1), directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin. (PMID:21076410)
• leucine zipper of Nek2 kinase is the first example where the frameshift of coiled-coil heptad repeats has been directly observed experimentally (PMID:21669869)
• The counteracting Nek2A and PP1gamma activities on the centrosome linker are controlled by Plk1. (PMID:21723128)
• Hec1 serine 165 (S165) is preferentially phosphorylated at kinetochores by Nek2 and it serves as an important mechanism in modulating spindle assemble checkpoint signaling and chromosome alignment. (PMID:21832156)
• This study suggests that abnormal expression of Nek2 and beta-catenin might be one of the mechanisms of tumorigenesis in breast cancer (PMID:22014044)
• Nek2A might bear a close relationship with development and progression of breast carcinoma, and have a role as a potential biomarker for diagnosis and a possible therapeutic target for human breast cancer especially for breast ductal carcinoma in situ. (PMID:22234886)
• The recruitment of Nek2 to the proximal ends of centrioles is dependent on one of its substrates, the centrosome cohesion protein C-Nap1. (PMID:22613497)
• Nek2 C downregulation, using RNA interference, decreased the survival, invasion and migration of MCF10DCIS.com and MCF10CA1a cells as well as in human primary breast cancer tissue. (PMID:22824957)
• Measuring IGF2BP3, HOXB7 and NEK2 mRNA levels by RT-PCR in addition to cytology has the potential to improve detection of malignant biliary disorders from brush cytology specimens. (PMID:22879911)
• Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women. (PMID:23001753)
• Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the spindle assembly checkpoint. (PMID:23288039)
• NEK2 phosphorylation antagonizes the microtubule stabilizing activity of centrobin. (PMID:23291182)
• small interfering RNA and antisense oligonucleotides against Nek2 worked synergistically with paclitaxel and doxorubicin by promoting cell apoptosis. (PMID:23340795)
• These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of BUB1B, PBK and NEK2 (PMID:23370767)
• these data indicate that Nek2 has a pivotal role in breast cancer growth at primary and secondary sites, and thus may be an attractive and novel therapeutic target for this disease. (PMID:23708664)
• Data conclude that centrosome amplification is modulated through Cdk4 and Nek2 signaling and that binucleation is a likely source of CA in Her2+ breast cancer cells. (PMID:23776583)
• Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. (PMID:24043777)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nek2	ENSDARG00000005619
mus_musculus	Nek2	ENSMUSG00000026622
rattus_norvegicus	Nek2l1	ENSRNOG00000004487
rattus_norvegicus	Nek2l1	ENSRNOG00000012119

Paralogs (8): NEK11 (ENSG00000114670), NEK6 (ENSG00000119408), NEK9 (ENSG00000119638), NEK3 (ENSG00000136098), NEK7 (ENSG00000151414), NEK8 (ENSG00000160602), NEK10 (ENSG00000163491), NEK5 (ENSG00000197168)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek2 — P51955 (reviewed: P51955)

Alternative names: HSPK 21, Never in mitosis A-related kinase 2, NimA-like protein kinase 1

All UniProt accessions (2): F6U4U2, P51955

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly. NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis. Involved in the regulation of centrosome disjunction. Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation. Phosphorylates and activates NEK11 in G1/S-arrested cells. Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells.

Subunit / interactions. Isoform 1, isoform 2 and isoform 4 form homo- and heterodimers. Interacts with NECAB3 and HMGA2. Isoform 1 interacts with CDC20, CTNB1, MAD1L1, MAPK, NEK11, NPM1, NDC80, PCNT and SGO1. Isoform 1 interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain). Isoform 1 and isoform 2 interact with MAD2L1. Isoform 1 and isoform 4 interact with PPP1CA and PPP1CC. Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN. Isoform 1 interacts with CEP85. Interacts with CCDC102B; the interaction leads to phosphorylation of CCDC102B.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Chromosome. Centromere. Kinetochore. Centromere Cytoplasm Nucleus.

Tissue specificity. Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up-regulated in various cancer cell lines, as well as primary breast tumors.

Post-translational modifications. Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome.

Disease relevance. Retinitis pigmentosa 67 (RP67) [MIM:615565] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Isoform 1 is inhibited by ionizing radiation in the presence of PPP1CA. Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix.

Domain organisation. The leucine-zipper domain is required for its dimerization and activation.

Induction. Expression and activity peak in the G2 phase of the mitotic cycle and decrease once the cells have entered mitosis due to degradation by the anaphase promoting complex APC/C-CDC20. In G1 phase, both isoform 1 and isoform 2 are almost undetectable. However, at the G1/S transition, there is an increase in expression of both isoforms which then remain at this increased level throughout S and G2. At the onset of mitosis, isoform 1 undergoes a rapid disappearance whereas isoform 2 continues to be present at about the same level as in G2. During the rest of mitosis, isoform 1 remains absent, while isoform 2 only begins to decline upon re-entry into the next G1 phase.

Similarity. Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P51955-1	1, Nek2A	yes
P51955-2	2, Nek2B
P51955-3	3
P51955-4	4, Nek2C, Nek2A-T

RefSeq proteins (3): NP_001191111, NP_001191112, NP_002488* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR051131	NEK_Ser/Thr_kinase_NIMA	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (76 total): modified residue 17, helix 16, mutagenesis site 12, strand 8, region of interest 6, splice variant 5, binding site 2, sequence variant 2, sequence conflict 2, coiled-coil region 2, chain 1, domain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
2W5A	X-RAY DIFFRACTION	1.55
2XNM	X-RAY DIFFRACTION	1.85
5M51	X-RAY DIFFRACTION	1.9
5M53	X-RAY DIFFRACTION	1.9
2XKD	X-RAY DIFFRACTION	1.96
2XNO	X-RAY DIFFRACTION	1.98
2XNP	X-RAY DIFFRACTION	1.98
2XK7	X-RAY DIFFRACTION	1.99
6SGD	X-RAY DIFFRACTION	2
6SGK	X-RAY DIFFRACTION	2
6SK9	X-RAY DIFFRACTION	2
2XK8	X-RAY DIFFRACTION	2
2XK4	X-RAY DIFFRACTION	2.1
2WQO	X-RAY DIFFRACTION	2.17
2JAV	X-RAY DIFFRACTION	2.2
2XK3	X-RAY DIFFRACTION	2.2
2XK6	X-RAY DIFFRACTION	2.2
2XKE	X-RAY DIFFRACTION	2.2
5M57	X-RAY DIFFRACTION	2.3
6SGI	X-RAY DIFFRACTION	2.3
2W5H	X-RAY DIFFRACTION	2.33
2XKF	X-RAY DIFFRACTION	2.35
2W5B	X-RAY DIFFRACTION	2.4
4A4X	X-RAY DIFFRACTION	2.4
5M55	X-RAY DIFFRACTION	2.4
2XKC	X-RAY DIFFRACTION	2.5
2XNN	X-RAY DIFFRACTION	2.5
4AFE	X-RAY DIFFRACTION	2.6
6SGH	X-RAY DIFFRACTION	3
6TM5	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51955-F1	78.52	0.40

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 (1): 141 (proton acceptor)

Ligand- & substrate-binding residues (2): 14–22; 37

Post-translational modifications (17): 170, 171, 175, 179, 184, 241, 296, 300, 356, 365, 387, 390, 397, 402, 406, 428, 438

Mutagenesis-validated functional residues (12):

Position	Phenotype
37	loss of kinase activity and of ability to activate nek11. loss of phosphorylation of ccdc102b.
141	loss of autophosphorylation.
170	no effect on kinase activity.
170	kinase activity increased by two fold.
171	no effect on kinase activity.
171	kinase activity increased by two fold.
175	kinase activity decreased by two fold.
175	kinase activity increased by two fold.
179	loss of kinase activity.
241	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)
R-HSA-1640170	Cell Cycle
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179419	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-453276	Regulation of mitotic cell cycle
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 471 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, LOPEZ_MESOTHELIOMA_SURVIVAL_DN, HORIUCHI_WTAP_TARGETS_DN, MODULE_451, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, GOBP_CHROMOSOME_LOCALIZATION, MORF_BRCA1

GO Biological Process (16): mitotic cell cycle (GO:0000278), blastocyst development (GO:0001824), chromosome segregation (GO:0007059), regulation of mitotic nuclear division (GO:0007088), positive regulation of telomere maintenance (GO:0032206), regulation of mitotic centrosome separation (GO:0046602), spindle assembly (GO:0051225), centrosome separation (GO:0051299), cell division (GO:0051301), meiotic cell cycle (GO:0051321), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), mitotic spindle assembly (GO:0090307), negative regulation of centriole-centriole cohesion (GO:1903126), mitotic sister chromatid segregation (GO:0000070), protein phosphorylation (GO:0006468), protein autophosphorylation (GO:0046777)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein phosphatase binding (GO:0019903), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (22): kinetochore (GO:0000776), condensed nuclear chromosome (GO:0000794), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), cilium (GO:0005929), midbody (GO:0030496), protein-containing complex (GO:0032991), ciliary basal body (GO:0036064), intercellular bridge (GO:0045171), chromosome, centromeric region (GO:0000775), condensed chromosome (GO:0000793), chromosome (GO:0005694), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Dengue Virus Infection	1
Regulation of PD-L1(CD274) Post-translational modification	1
Regulation of mitotic cell cycle	1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC/C-mediated degradation of cell cycle proteins	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitotic nuclear division	4
intracellular membraneless organelle	4
regulation of cell cycle process	3
cell cycle	2
cell cycle process	2
protein kinase activity	2
nuclear lumen	2
microtubule organizing center	2
in utero embryonic development	1
anatomical structure development	1
regulation of mitotic cell cycle	1
regulation of nuclear division	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
mitotic centrosome separation	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
centrosome cycle	1
cellular process	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
attachment of spindle microtubules to kinetochore	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
centriole-centriole cohesion	1
negative regulation of cell cycle process	1
regulation of centriole-centriole cohesion	1
sister chromatid segregation	1
mitotic cell cycle process	1
phosphorylation	1
protein modification process	1
protein phosphorylation	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Protein interactions and networks

STRING

3311 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK2	CEP250	Q9BV73	894
NEK2	CROCC	Q5TZA2	883
NEK2	NDC80	O14777	854
NEK2	CENPF	P49454	759
NEK2	PTTG1	O95997	756
NEK2	KIF11	P52732	746
NEK2	NECAB3	Q96P71	735
NEK2	CCNB2	O95067	717
NEK2	PCNT	O95613	715
NEK2	TPX2	Q9ULW0	696
NEK2	DLGAP5	Q15398	691
NEK2	TOP2A	P11388	685
NEK2	NUF2	Q9BZD4	682
NEK2	CCNA2	P20248	681
NEK2	KIF20A	O95235	678

IntAct

88 interactions, top by confidence:

A	B	Type	Score
ANAPC4	BUB1B	psi-mi:“MI:0914”(association)	0.820
ANAPC5	CDC27	psi-mi:“MI:0914”(association)	0.810
CDC16	BUB1B	psi-mi:“MI:0914”(association)	0.790
CDC23	BUB1B	psi-mi:“MI:0914”(association)	0.790
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730
ANAPC2	BUB1B	psi-mi:“MI:0914”(association)	0.730
CDC26	BUB1B	psi-mi:“MI:0914”(association)	0.640
KIF24	NEK2	psi-mi:“MI:0915”(physical association)	0.620
NEK2	KIF24	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
NEK2	KIF24	psi-mi:“MI:0403”(colocalization)	0.620
CDC27	NEK2	psi-mi:“MI:0914”(association)	0.620
NEK11	NEK2	psi-mi:“MI:0403”(colocalization)	0.620
NEK11	NEK2	psi-mi:“MI:0915”(physical association)	0.620
NEK2	NEK11	psi-mi:“MI:0915”(physical association)	0.620
NEK2	NEK11	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
ANAPC4	NEK2	psi-mi:“MI:0914”(association)	0.620
NEK2	ANAPC4	psi-mi:“MI:0915”(physical association)	0.620
NEK2	CDC27	psi-mi:“MI:0915”(physical association)	0.620
NEK2	PPP1CC	psi-mi:“MI:0407”(direct interaction)	0.590
NEK2	PPP1CC	psi-mi:“MI:0915”(physical association)	0.590
Cdc23	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
Cdc16	BUB1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (209): NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-Western), NEK2 (Affinity Capture-Western), NEK2 (Affinity Capture-Western), PPP1CC (Far Western), NEK2 (Two-hybrid), NEK2 (Proximity Label-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS), NEK2 (Affinity Capture-MS)

ESM2 similar proteins: A7MBL8, F1QGZ6, O14757, O35099, O35280, O54785, O54992, P45983, P45984, P49185, P49186, P49187, P51955, P53350, P53666, P53668, P53670, P53671, P53779, P62205, P70032, Q07832, Q14680, Q15835, Q16513, Q28GW8, Q2RAX3, Q2TA25, Q32L23, Q3SZW1, Q61241, Q61831, Q61846, Q62673, Q63651, Q6DE87, Q6NU47, Q6NU98, Q8AYC9, Q8IW41

Diamond homologs: A0A078CGE6, A2BD05, A2QHV0, A2ZMH2, A7SNN5, D3ZBE5, D3ZGQ5, E9Q3S4, G5EFM9, H2L099, O01775, O13839, O14047, O22040, O22042, O35942, O61122, P11837, P22209, P41892, P48479, P48963, P51954, P51955, P51956, P51957, P59895, P84199, Q03428, Q08942, Q0CL79, Q0KHQ5, Q0WPH8, Q10GB1, Q2QAV0, Q2QMH1, Q3SWY6, Q3UGM2, Q40541, Q4FZD7

SIGNOR signaling

35 interactions.

A	Effect	B	Mechanism
NEK2	up-regulates	NEK11	phosphorylation
PCM1	up-regulates	NEK2	relocalization
NEK2	up-regulates	NEK2	phosphorylation
NEK2	down-regulates	NEK2	phosphorylation
PPP1CA	down-regulates	NEK2	dephosphorylation
NEK2	up-regulates	SGO1	phosphorylation
STK3	up-regulates	NEK2	phosphorylation
NEK2	down-regulates	CEP250	phosphorylation
NEK2	down-regulates	PP1	phosphorylation
PP1	down-regulates	NEK2	dephosphorylation
NEK2	“up-regulates activity”	GAS2L1	phosphorylation
NEK2	“down-regulates activity”	LRRC45	phosphorylation
NEK2	“down-regulates quantity”	CTNNB1	phosphorylation
NEK2	“up-regulates activity”	CDC20	phosphorylation
NEK2	“up-regulates activity”	KIF24	phosphorylation
NEK2	“down-regulates activity”	MAD2L1	phosphorylation
NEK2	down-regulates	TP53	phosphorylation
NEK2	“down-regulates activity”	NCAPD2	phosphorylation
NEK2	“up-regulates activity”	SUFU	phosphorylation
NEK2	“down-regulates activity”	SRSF1	phosphorylation
NEK2	“down-regulates quantity by destabilization”	CEP68	phosphorylation
NEK2	“down-regulates activity”	CNTROB	phosphorylation
NEK2	down-regulates	PPP1CC	phosphorylation

Enriched among interaction partners

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

Reactome pathways:

Pathway	Partners	Fold	FDR
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	11	174.5×	1e-21
Inactivation of APC/C via direct inhibition of the APC/C complex	11	142.8×	2e-20
Phosphorylation of the APC/C	9	122.4×	2e-16
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	9	116.8×	2e-16
Aberrant regulation of mitotic exit in cancer due to RB1 defects	9	116.8×	2e-16
APC-Cdc20 mediated degradation of Nek2A	11	116.3×	1e-19
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	11	116.3×	1e-19
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	11	112.2×	2e-19

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	9	148.7×	6e-16
regulation of meiotic cell cycle	9	135.2×	9e-16
anaphase-promoting complex-dependent catabolic process	9	123.9×	2e-15
protein K11-linked ubiquitination	9	69.2×	4e-13
regulation of mitotic cell cycle	9	42.5×	4e-11
protein K48-linked ubiquitination	9	29.7×	8e-10
cell division	17	15.4×	2e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	172
Likely benign	79
Benign	11

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
91391	NM_002497.4(NEK2):c.617_624delinsA (p.Leu206fs)	Pathogenic
3028564	NM_002497.4(NEK2):c.1270del (p.Ala424fs)	Likely pathogenic
3028575	NM_002497.4(NEK2):c.1027G>A (p.Asp343Asn)	Likely pathogenic
3028579	NM_002497.4(NEK2):c.1010G>C (p.Arg337Pro)	Likely pathogenic
3028597	NM_002497.4(NEK2):c.618_624del (p.Glu208fs)	Likely pathogenic

SpliceAI

1040 predictions. Top by Δscore:

Variant	Effect	Δscore
1:211667100:TCATA:T	donor_loss	1.0000
1:211667102:ATAC:A	donor_loss	1.0000
1:211667103:TA:T	donor_loss	1.0000
1:211667104:AC:A	donor_loss	1.0000
1:211667105:C:CA	donor_loss	1.0000
1:211667133:T:TA	donor_gain	1.0000
1:211667227:TTTCT:T	acceptor_gain	1.0000
1:211667228:TTCT:T	acceptor_gain	1.0000
1:211667230:CT:C	acceptor_gain	1.0000
1:211667232:C:CC	acceptor_gain	1.0000
1:211667233:T:C	acceptor_gain	1.0000
1:211667233:T:TC	acceptor_gain	1.0000
1:211667234:T:C	acceptor_gain	1.0000
1:211667234:T:TC	acceptor_gain	1.0000
1:211667245:A:AC	acceptor_gain	1.0000
1:211667245:A:C	acceptor_gain	1.0000
1:211669107:ACTTA:A	donor_loss	1.0000
1:211669108:CTT:C	donor_loss	1.0000
1:211669111:A:AC	donor_gain	1.0000
1:211669111:A:AG	donor_loss	1.0000
1:211669111:ACG:A	donor_gain	1.0000
1:211669111:ACGCT:A	donor_gain	1.0000
1:211669112:C:CA	donor_gain	1.0000
1:211669112:CG:C	donor_gain	1.0000
1:211669112:CGC:C	donor_gain	1.0000
1:211669112:CGCT:C	donor_gain	1.0000
1:211669112:CGCTC:C	donor_gain	1.0000
1:211669115:T:A	donor_gain	1.0000
1:211669330:ATCC:A	acceptor_loss	1.0000
1:211669331:TC:T	acceptor_gain	1.0000

AlphaMissense

2914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:211669323:G:C	R259G	1.000
1:211670375:A:G	L224P	1.000
1:211670398:A:C	F216L	1.000
1:211670398:A:T	F216L	1.000
1:211670399:A:G	F216S	1.000
1:211670400:A:G	F216L	1.000
1:211670402:G:T	P215Q	1.000
1:211671228:G:C	C204W	1.000
1:211671232:C:T	G203D	1.000
1:211671233:C:G	G203R	1.000
1:211671239:A:G	S201P	1.000
1:211671240:C:A	W200C	1.000
1:211671240:C:G	W200C	1.000
1:211671242:A:G	W200R	1.000
1:211671242:A:T	W200R	1.000
1:211671247:T:A	D198V	1.000
1:211671247:T:C	D198G	1.000
1:211671247:T:G	D198A	1.000
1:211671248:C:A	D198Y	1.000
1:211671248:C:G	D198H	1.000
1:211673484:G:T	P185H	1.000
1:211673487:G:A	S184F	1.000
1:211673494:A:G	Y182H	1.000
1:211673502:G:A	T179I	1.000
1:211673505:C:T	G178D	1.000
1:211673506:C:G	G178R	1.000
1:211673508:A:T	V177D	1.000
1:211673550:G:T	A163D	1.000
1:211673556:C:T	G161E	1.000
1:211673559:A:G	F160S	1.000

dbSNP variants (sampled 300 via entrez): RS1000313915 (1:211677087 C>T), RS1000674023 (1:211673984 C>G), RS1000771069 (1:211658245 G>A), RS1000935500 (1:211662638 A>T), RS1001179214 (1:211677316 C>T), RS1001210291 (1:211677614 T>C), RS1001549266 (1:211666235 A>C), RS1001807997 (1:211665324 G>T), RS1001884301 (1:211664824 ATTTTGT>A), RS1001904839 (1:211658219 G>A), RS1002380294 (1:211672841 T>C), RS1002427553 (1:211671997 T>C), RS1002486799 (1:211661633 G>A), RS1002549140 (1:211667752 A>G), RS1002755537 (1:211672529 C>A)

Disease associations

OMIM: gene MIM:604043 | disease phenotypes: MIM:615565

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 67	Moderate	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

Mondo (3): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 67 (MONDO:0014256), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology
HP:0011505	Cystoid macular edema
HP:0012426	Optic disc drusen
HP:0030466	Abnormal full-field electroretinogram

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004621_43	Red cell distribution width	5.000000e-13
GCST006804_168	Red cell distribution width	3.000000e-09
GCST90002404_445	Red cell distribution width	4.000000e-09
GCST90011900_29	Serum alkaline phosphatase levels	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3835 (SINGLE PROTEIN), CHEMBL4524130 (PROTEIN FAMILY), CHEMBL4802034 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 250,157 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL50	QUERCETIN	3	74,559
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908394	GSK-461364	1
CHEMBL1908397	KW-2449	1
CHEMBL482967	CYC-116	1

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NIMA (never in mitosis gene a)- related kinase (NEK) family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 2 [PMID: 21627121]	Inhibition	8.22	pIC50
GSK579289A	Inhibition	7.68	pIC50
compound 31 [PMID: 20936789]	Inhibition	6.64	pIC50

Binding affinities (BindingDB)

21 measured of 28 human assays (28 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
(E)-2-cyano-3-[3-(3,4,5-trimethoxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]prop-2-enamide	IC50	14 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-N-methyl-3-[3-(3,4,5-trimethoxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]prop-2-enamide	IC50	14 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-N,N-dimethyl-3-[3-(3,4,5-trimethoxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]prop-2-enamide	IC50	89 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-N-methyl-3-[1-(7H-purin-6-yl)piperidin-4-yl]prop-2-enamide	IC50	440 nM	US-9505766: Kinase inhibitors
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(E)-2-cyano-3-(1H-indazol-6-yl)-N-propan-2-ylprop-2-enamide	IC50	630 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-3-[1-(7H-purin-6-yl)piperidin-4-yl]prop-2-enamide	IC50	758 nM	US-9505766: Kinase inhibitors
(E)-3-(1H-indazol-5-yl)-2-(pyrrolidine-1-carbonyl)prop-2-enenitrile	IC50	1000 nM	US-9505766: Kinase inhibitors
(E)-2-methylsulfonyl-3-[3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl]prop-2-enenitrile	IC50	1000 nM	US-9505766: Kinase inhibitors
(E)-3-(1H-indazol-6-yl)-2-(pyrrolidine-1-carbonyl)prop-2-enenitrile	IC50	2600 nM	US-9505766: Kinase inhibitors
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
(E)-2-cyano-3-[3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl]prop-2-enamide	IC50	40000 nM	US-9505766: Kinase inhibitors
(E)-2-methylsulfonyl-3-[4-(7H-purin-6-yl)phenyl]prop-2-enenitrile	IC50	60000 nM	US-9505766: Kinase inhibitors
(E)-2-(benzenesulfonyl)-3-[4-(7H-purin-6-yl)phenyl]prop-2-enenitrile	IC50	60000 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-3-[4-(7H-purin-6-yl)phenyl]prop-2-enamide	IC50	100000 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-3-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl]prop-2-enamide	IC50	150000 nM	US-9505766: Kinase inhibitors
(E)-2-cyano-3-(4-pyridin-4-ylphenyl)prop-2-enamide	IC50	150000 nM	US-9505766: Kinase inhibitors

ChEMBL bioactivities

461 potent at pChembl≥5 of 515 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL4062453
8.52	IC50	3	nM	CHEMBL4063211
8.49	IC50	3.2	nM	CHEMBL4860697
8.15	IC50	7	nM	CHEMBL4091089
8.12	Kd	7.634	nM	CHEMBL3752910
8.00	IC50	10	nM	CHEMBL4763380
8.00	IC50	10	nM	CHEMBL4761747
7.96	ED50	11.01	nM	CHEMBL3752910
7.90	Ki	12.59	nM	ILORASERTIB
7.90	Ki	12.59	nM	CHEMBL2006778
7.89	IC50	13	nM	ILORASERTIB
7.78	IC50	16.65	nM	CHEMBL6191436
7.75	IC50	18	nM	CHEMBL4786783
7.70	IC50	20	nM	CHEMBL1802383
7.70	Ki	19.95	nM	CHEMBL1241473
7.68	IC50	21	nM	GSK-579289A
7.66	IC50	22	nM	CHEMBL2042135
7.60	IC50	25	nM	CHEMBL1615278
7.58	IC50	26	nM	CHEMBL4796125
7.50	Ki	31.62	nM	CHEMBL1988581
7.46	IC50	34.27	nM	CHEMBL6188451
7.43	IC50	37	nM	CHEMBL2042136
7.41	IC50	39	nM	CHEMBL4743876
7.40	IC50	40	nM	CHEMBL1997822
7.40	IC50	39.9	nM	CHEMBL2023348
7.40	Ki	39.81	nM	CHEMBL1981725
7.40	Ki	39.81	nM	CHEMBL1997822
7.38	IC50	42	nM	CHEMBL4779487
7.33	IC50	47	nM	CHEMBL2042035
7.33	IC50	47	nM	CHEMBL2042036
7.30	IC50	50	nM	CHEMBL4775990
7.30	IC50	50	nM	CHEMBL3646210
7.30	IC50	50	nM	CHEMBL1689158
7.30	Ki	50.12	nM	CHEMBL1989708
7.24	IC50	58	nM	CHEMBL2042037
7.24	IC50	57	nM	CHEMBL4796754
7.24	IC50	57	nM	CHEMBL4783060
7.23	IC50	59	nM	CHEMBL2042040
7.22	IC50	60	nM	CHEMBL1802382
7.21	IC50	62	nM	CHEMBL4786783
7.20	Ki	63.1	nM	CHEMBL1970317
7.20	Ki	63.1	nM	CHEMBL1973359
7.20	Ki	63.1	nM	CHEMBL1970142
7.20	Ki	63.1	nM	CHEMBL2002165
7.20	Ki	63.1	nM	CHEMBL1967116
7.19	IC50	64	nM	CHEMBL4748191
7.15	IC50	71	nM	CHEMBL4795738
7.14	IC50	73	nM	CHEMBL2042041
7.14	IC50	72	nM	CHEMBL4746054
7.12	IC50	76	nM	CHEMBL4783265

PubChem BioAssay actives

218 with measured affinity, of 2690 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
4-[7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-[(3-fluorophenyl)methoxy]benzamide	1436372: Inhibition of N-terminal His6-tagged full-length recombinant human NEK2 expressed in baculovirus infected sf21 cells using biotin labelled-STK-3 substrate measured after 60 mins by HTRF assay	ic50	0.0010	uM
4-[7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-phenylmethoxybenzamide	1436372: Inhibition of N-terminal His6-tagged full-length recombinant human NEK2 expressed in baculovirus infected sf21 cells using biotin labelled-STK-3 substrate measured after 60 mins by HTRF assay	ic50	0.0030	uM
5-[7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	1771727: Inhibition of NEK2 (unknown origin) using 5’ FAM-KKLNRTLSVA-COOH peptide as a substrate in the presence of ATP incubated for 60 mins by microfluidics assay	ic50	0.0032	uM
(3Z)-5-(2-chloroacetyl)-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one	606553: Inhibition of human Nek2 in using [gamma-32P] ATP	ic50	0.0060	uM
4-[7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-[[3-(trifluoromethyl)phenyl]methoxy]benzamide	1436372: Inhibition of N-terminal His6-tagged full-length recombinant human NEK2 expressed in baculovirus infected sf21 cells using biotin labelled-STK-3 substrate measured after 60 mins by HTRF assay	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	2148861: Binding affinity to human NEK2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0076	uM
1-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N,N-dimethylmethanesulfonamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0100	uM
7-[(6-ethynyl-7H-purin-2-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0100	uM
1-[4-[4-amino-7-[1-(2-hydroxyethyl)pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl]phenyl]-3-(3-fluorophenyl)urea	1948853: Inhibition of NEK2 (unknown origin)	ic50	0.0130	uM
2-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]acetamide	1695308: Inhibition of human NEK2 by kinase-profiling analysis	ic50	0.0180	uM
(3Z)-5-(2-chloroacetyl)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-1H-indol-2-one	606553: Inhibition of human Nek2 in using [gamma-32P] ATP	ic50	0.0200	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-(1-methylpiperidin-4-yl)oxybenzimidazol-1-yl]thiophene-2-carboxamide	418653: Inhibition of human Nek2	ic50	0.0210	uM
4-[2-amino-5-[4-[(dimethylamino)methyl]thiophen-2-yl]-3-pyridinyl]-2-[(Z,2R)-5,5,5-trifluoropent-3-en-2-yl]oxybenzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0220	uM
5-[6-(1-methylpiperidin-4-yl)oxybenzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	418653: Inhibition of human Nek2	ic50	0.0250	uM
3-[(6-ethynyl-7H-purin-2-yl)amino]-N-methylbenzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0260	uM
4-[2-amino-5-[4-[(dimethylamino)methyl]thiophen-2-yl]-3-pyridinyl]-2-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0370	uM
N-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]acetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0390	uM
3-(2-methyl-1H-indol-5-yl)-7-(3-methylsulfonylphenyl)thieno[3,2-c]pyridin-4-amine	1948853: Inhibition of NEK2 (unknown origin)	ic50	0.0400	uM
7-[(6-ethynyl-7H-purin-2-yl)amino]-2-methyl-1,4-dihydroisoquinolin-3-one	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0420	uM
4-[2-amino-5-[5-[(dimethylamino)methyl]thiophen-2-yl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0470	uM
4-[2-amino-5-[5-[(dimethylamino)methyl]-4-methylthiophen-2-yl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0470	uM
3-[(6-ethynyl-7H-purin-2-yl)amino]-N,N-dimethylbenzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0500	uM
5-[6-(1-methylpiperidin-4-yl)oxybenzimidazol-1-yl]-3-[1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	587106: Inhibition of NEK2 autophosphorylation preincubated with compound by DELFIA assay	ic50	0.0500	uM
1-[4-[4-amino-7-[1-[(2S)-2-hydroxypropyl]pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl]phenyl]-3-(3-methylphenyl)urea	1948853: Inhibition of NEK2 (unknown origin)	ic50	0.0500	uM
6-ethynyl-N-[3-(methylsulfonylmethyl)phenyl]-7H-purin-2-amine	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0570	uM
2-[4-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N,N-dimethylacetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0570	uM
4-[2-amino-5-[5-[(dimethylamino)methyl]-3-methylthiophen-2-yl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0580	uM
4-[2-amino-5-[4-[(dimethylamino)methyl]thiophen-2-yl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0590	uM
(3Z)-5-(2-chloroacetyl)-3-(1H-imidazol-5-ylmethylidene)-1H-indol-2-one	606553: Inhibition of human Nek2 in using [gamma-32P] ATP	ic50	0.0600	uM
4-[(6-ethynyl-7H-purin-2-yl)amino]-N,N-dimethylbenzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0640	uM
2-[4-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N,N’-dimethylpropanediamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0710	uM
2-[4-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N-methylacetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0720	uM
4-[2-amino-5-[4-[(dimethylamino)methyl]thiophen-2-yl]-3-pyridinyl]-2-[(Z)-5,5,5-trifluoropent-3-en-2-yl]oxybenzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0730	uM
1-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]propan-2-one	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0760	uM
2-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N-methylacetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0760	uM
3-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]propanamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0790	uM
4-[7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-[(2-fluorophenyl)methoxy]benzamide	1436372: Inhibition of N-terminal His6-tagged full-length recombinant human NEK2 expressed in baculovirus infected sf21 cells using biotin labelled-STK-3 substrate measured after 60 mins by HTRF assay	ic50	0.0870	uM
2-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]-N,N-dimethylacetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0880	uM
2-[4-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]acetamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.0930	uM
4-[2-amino-5-[5-(piperidin-1-ylmethyl)thiophen-2-yl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.0930	uM
5-[(6-ethynyl-7H-purin-2-yl)amino]-1,3-dihydroindol-2-one	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1000	uM
4-[(6-ethynyl-7H-purin-2-yl)amino]benzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1100	uM
4-[(6-ethynyl-7H-purin-2-yl)amino]-N-methylbenzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1100	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	1948823: Inhibition of NEK2 (unknown origin) assessed as dissociation constant	kd	0.1100	uM
3-[(6-ethynyl-7H-purin-2-yl)amino]benzamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1160	uM
4-[2-amino-5-[4-[(dimethylamino)methyl]phenyl]-3-pyridinyl]-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzamide	667093: Inhibition of Nek2 using 5-FAM-KKLNRTLSVA-COOH as substrate after 1 hr by caliper method	ic50	0.1200	uM
[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]methanesulfonamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1300	uM
(3Z)-5-(2-chloroacetyl)-3-[(2-ethyl-5-methyl-1H-imidazol-4-yl)methylidene]-1H-indol-2-one	606553: Inhibition of human Nek2 in using [gamma-32P] ATP	ic50	0.1300	uM
4-[(6-ethynyl-7H-purin-2-yl)amino]benzenesulfonamide	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1400	uM
6-ethynyl-N-phenyl-7H-purin-2-amine	1695304: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis	ic50	0.1400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	decreases expression	3
Cyclosporine	decreases expression	3
deguelin	increases expression, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	decreases expression, affects cotreatment, increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression	2
Coumestrol	affects reaction, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
trichostatin A	affects expression	1
methylparaben	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
cryptolepine	decreases expression	1
ferrous chloride	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
diallyl trisulfide	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
bicalutamide	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1

ChEMBL screening assays

471 unique, capped per target: 469 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000635	Binding	Inhibition of NEK2a at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963823	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NEK2	PubChem BioAssay data set
CHEMBL4832371	ADMET	Inhibition of NEK2 (unknown origin)	Discovery and biological evaluation of phthalazines as novel non-kinase TGFβ pathway inhibitors. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9VQ	Abcam HeLa NEK2 KO	Cancer cell line	Female
CVCL_TA35	HAP1 NEK2 (-) 1	Cancer cell line	Male
CVCL_TA36	HAP1 NEK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa