NEK3

Summary

NEK3 (NIMA related kinase 3, HGNC:7746) is a protein-coding gene on chromosome 13q14.3, encoding Serine/threonine-protein kinase Nek3 (P51956). Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules.

This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein differs from other NimA family members in that it is not cell cycle regulated and is found primarily in the cytoplasm. The kinase is activated by prolactin stimulation, leading to phosphorylation of VAV2 guanine nucleotide exchange factor, paxillin, and activation of the RAC1 GTPase. Two functional alleles for this gene have been identified in humans. The reference genome assembly (GRCh38) represents a functional allele that is associated with the inclusion of an additional coding exon in protein-coding transcripts, compared to an alternate functional allele that lacks the exon.

Source: NCBI Gene 4752 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7746
Approved symbol	NEK3
Name	NIMA related kinase 3
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Aliases	HSPK36, MGC29949
Ensembl gene	ENSG00000136098
Ensembl biotype	protein_coding
OMIM	604044
Entrez	4752

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000550331, ENST00000550841, ENST00000551355, ENST00000552973, ENST00000610828, ENST00000617054, ENST00000618534, ENST00000618856, ENST00000620675, ENST00000858785, ENST00000858786, ENST00000858787, ENST00000913399, ENST00000913400, ENST00000913401, ENST00000913402, ENST00000913403, ENST00000962648, ENST00000962649

RefSeq mRNA: 13 — MANE Select: NM_002498 NM_001424254, NM_001424255, NM_001424257, NM_001424259, NM_001424264, NM_001424265, NM_001424266, NM_001424268, NM_001424269, NM_001424270, NM_001424271, NM_002498, NM_152720

CCDS: CCDS73576

Canonical transcript exons

ENST00000610828 — 16 exons

Exon	Start	End
ENSE00003492462	52156075	52156248
ENSE00003721633	52135729	52135863
ENSE00003724728	52141020	52141069
ENSE00003724789	52153895	52153992
ENSE00003727898	52144691	52144891
ENSE00003728538	52133689	52133815
ENSE00003733546	52136800	52136902
ENSE00003735854	52152609	52152692
ENSE00003737224	52136116	52136259
ENSE00003738064	52143915	52143987
ENSE00003738962	52148415	52148469
ENSE00003743792	52151146	52151232
ENSE00003745738	52151325	52151392
ENSE00003747946	52154080	52154173
ENSE00003841848	52159543	52159597
ENSE00003849692	52132647	52133226

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5237 / max 108.5483, expressed in 1545 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137413	3.7492	1471
207041	0.3252	180
137411	0.1979	89
137415	0.1517	49
137412	0.0671	30
137414	0.0260	7
207040	0.0065	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	93.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.91	gold quality
mucosa of transverse colon	UBERON:0004991	92.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.91	gold quality
right testis	UBERON:0004534	91.24	gold quality
left testis	UBERON:0004533	91.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.73	gold quality
testis	UBERON:0000473	90.22	gold quality
tibial nerve	UBERON:0001323	90.04	gold quality
rectum	UBERON:0001052	89.46	gold quality
corpus callosum	UBERON:0002336	89.42	gold quality
calcaneal tendon	UBERON:0003701	89.36	gold quality
transverse colon	UBERON:0001157	89.33	gold quality
spinal cord	UBERON:0002240	88.84	gold quality
tendon	UBERON:0000043	88.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.82	gold quality
mucosa of stomach	UBERON:0001199	87.75	gold quality
endocervix	UBERON:0000458	87.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.10	gold quality
right lung	UBERON:0002167	86.72	gold quality
tendon of biceps brachii	UBERON:0008188	86.68	gold quality
body of uterus	UBERON:0009853	86.61	gold quality
small intestine	UBERON:0002108	86.23	gold quality
medial globus pallidus	UBERON:0002477	86.05	gold quality
intestine	UBERON:0000160	86.02	gold quality
right ovary	UBERON:0002118	86.01	gold quality
descending thoracic aorta	UBERON:0002345	85.97	gold quality
large intestine	UBERON:0000059	85.92	gold quality
colon	UBERON:0001155	85.87	gold quality
ascending aorta	UBERON:0001496	85.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3). (PMID:12063396)
• Nek3 insertion/deletion polymorphism with alterations at 13q14 is associated with cancers (PMID:17118778)
• Nek3 contributes to prolactin-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation. (PMID:17297458)
• EHD2 interacts with Nek3 [NIMA (never in mitosis in Aspergillus nidulans)-related kinase 3], a serine/threonine kinase. (PMID:21756249)
• these data support a modulatory role for phosphorylation at NEK3 Thr-165 in focal adhesion maturation and/or turnover to promote breast cancer cell migration. (PMID:27489110)
• NEK3 kinase phosphorylates SNAP29 on its serine 105. NEK3-mediated phosphorylation determines membrane localization of SNAP29. Membrane-associated SNAP29 regulates Golgi and focal adhesion structures. (PMID:29454964)
• The data demonstrate that NEK3 is overexpressed in gastric cancer, which promotes the malignancy of gastric cancer (PMID:29504992)
• the NEK protein kinases emerge as important proteins in thyroid cancer development and may help to identify malignancy and aggressiveness features during diagnosis. (PMID:31906878)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000058869
mus_musculus	Nek3	ENSMUSG00000031478
rattus_norvegicus	Nek3	ENSRNOG00000012757

Paralogs (8): NEK11 (ENSG00000114670), NEK2 (ENSG00000117650), NEK6 (ENSG00000119408), NEK9 (ENSG00000119638), NEK7 (ENSG00000151414), NEK8 (ENSG00000160602), NEK10 (ENSG00000163491), NEK5 (ENSG00000197168)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek3 — P51956 (reviewed: P51956)

Alternative names: HSPK 36, Never in mitosis A-related kinase 3

All UniProt accessions (6): A0A087WY58, A0A087X030, A0A087X203, P51956, F8VTT4, F8VV00

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2.

Subunit / interactions. Interacts with PXN, PRLR, VAV1 and VAV2 and this interaction is prolactin-dependent.

Subcellular location. Cytoplasm. Cell projection. Axon.

Tissue specificity. Up-regulated in malignant versus normal breast tissue. Isoform 2 shows a high level of expression in testis, ovary and brain.

Post-translational modifications. Phosphorylation at Thr-479 regulates its catalytic activity.

Activity regulation. Prolactin stimulates its activity.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51956-1	1	yes
P51956-2	2

RefSeq proteins (13): NP_001411183, NP_001411184, NP_001411186, NP_001411188, NP_001411193, NP_001411194, NP_001411195, NP_001411197, NP_001411198, NP_001411199, NP_001411200, NP_002489, NP_689933 (=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
IPR017441	Protein_kinase_ATP_BS	Binding_site

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 (26 total): sequence variant 8, sequence conflict 4, modified residue 3, region of interest 3, compositionally biased region 2, binding site 2, chain 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51956-F1	65.52	0.31

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): 127 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Post-translational modifications (3): 1, 161, 479

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, CEBALLOS_TARGETS_OF_TP53_AND_MYC_UP, ONKEN_UVEAL_MELANOMA_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_MITOTIC_CELL_CYCLE, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, GOCC_NEURON_PROJECTION, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP, MODULE_342, chr13q14, GOBP_CELL_DIVISION

GO Biological Process (3): mitotic cell cycle (GO:0000278), protein phosphorylation (GO:0006468), cell division (GO:0051301)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), axon (GO:0030424), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
phosphorylation	1
protein modification process	1
cellular process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK3	TPTE	P56180	785
NEK3	RCC1L	Q96I51	629
NEK3	DNAJC6	O75061	583
NEK3	VAV1	P15498	570
NEK3	BICD2	Q8TD16	545
NEK3	RCC1	P18754	489
NEK3	CROCC	Q5TZA2	391
NEK3	CSN2	P05814	386
NEK3	PRLR	P16471	373
NEK3	VAV2	P52735	348
NEK3	HIPK4	Q8NE63	326
NEK3	NEK2	P51955	325
NEK3	TCHP	Q9BT92	318
NEK3	PRL	P01236	312
NEK3	CALML3	P27482	305

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CDK13	CCNK	psi-mi:“MI:0914”(association)	0.830
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
CPNE2	HIP1	psi-mi:“MI:0914”(association)	0.530
NEK3	PRLR	psi-mi:“MI:0915”(physical association)	0.400
NEK3	VAV2	psi-mi:“MI:0915”(physical association)	0.400
VAV2	NEK3	psi-mi:“MI:0915”(physical association)	0.400
NEK3	BPGM	psi-mi:“MI:0915”(physical association)	0.370
CDCA8	NEK3	psi-mi:“MI:0915”(physical association)	0.370
NMNAT1	NEK3	psi-mi:“MI:0915”(physical association)	0.370
KATNB1	TUBA8	psi-mi:“MI:0914”(association)	0.350
CDK13	CCNK	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
CPNE2	SUPT5H	psi-mi:“MI:0914”(association)	0.350
NEK3	KATNA1	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Affinity Capture-MS), NEK3 (Proximity Label-MS), KATNA1 (Affinity Capture-MS), SON (Affinity Capture-MS), TMPO (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A0A1L8I2C5, A1A5R7, A6PWY4, A9X1C6, B1ANS9, B2KIQ4, D3Z3I0, E9Q7R9, F1QHZ6, O13286, O74845, O94411, P26309, P43254, P51956, P93471, Q09786, Q4V837, Q5R6T6, Q5TKR9, Q5XHI9, Q5ZKI7, Q6DTM3, Q6GM71, Q6GPU3, Q6VZ17, Q7Z2W4, Q80Z32, Q86VD1, Q86Y33, Q8BZ21, Q8CDP0, Q8K3E5, Q8L4H0, Q8N157, Q8N4N8, Q8NA75, Q8NDM7, Q8NEM8

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A2QHV0, A8XJQ6, C4YRB7, O13839, O14047, O34507, O75011, O80888, O88664, P0CY23, P0CY24, P16912, P27636, P28829, P34722, P41892, P50527, P51956, P51957, P92199, P93025, P9WI62, P9WI63, Q0CL79, Q0KHQ5, Q0WPH8, Q12851, Q12852, Q19192, Q1DB00, Q4P5N0, Q53UA7, Q55CA6, Q55D99, Q55DD4, Q55GV3, Q5AP97

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NEK3	“up-regulates activity”	SNAP29	phosphorylation
NEK3	“down-regulates activity”	NEK3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2090 predictions. Top by Δscore:

Variant	Effect	Δscore
13:52133225:CC:C	acceptor_gain	1.0000
13:52133226:CC:C	acceptor_gain	1.0000
13:52133227:CTGTG:C	acceptor_loss	1.0000
13:52133228:T:A	acceptor_loss	1.0000
13:52133677:A:AC	donor_gain	1.0000
13:52133687:A:AC	donor_gain	1.0000
13:52133688:C:CA	donor_gain	1.0000
13:52133688:CGTGT:C	donor_gain	1.0000
13:52133695:T:TA	donor_gain	1.0000
13:52133820:A:T	acceptor_gain	1.0000
13:52133825:A:AC	acceptor_gain	1.0000
13:52133825:A:C	acceptor_gain	1.0000
13:52133827:A:C	acceptor_gain	1.0000
13:52133828:T:TC	acceptor_gain	1.0000
13:52136271:G:GC	acceptor_gain	1.0000
13:52136795:CTTA:C	donor_loss	1.0000
13:52136797:TA:T	donor_loss	1.0000
13:52136799:C:CA	donor_loss	1.0000
13:52136899:CTTG:C	acceptor_gain	1.0000
13:52136900:TTGC:T	acceptor_loss	1.0000
13:52136903:C:CC	acceptor_gain	1.0000
13:52136904:T:C	acceptor_gain	1.0000
13:52136905:T:C	acceptor_gain	1.0000
13:52136905:T:TC	acceptor_gain	1.0000
13:52143909:TCTTA:T	donor_loss	1.0000
13:52143910:CTTAC:C	donor_loss	1.0000
13:52143911:TTACT:T	donor_loss	1.0000
13:52143912:TACT:T	donor_loss	1.0000
13:52143913:A:AC	donor_gain	1.0000
13:52143913:ACT:A	donor_loss	1.0000

AlphaMissense

3366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:52144762:G:T	R245S	0.999
13:52148462:A:G	W186R	0.999
13:52148462:A:T	W186R	0.999
13:52144762:G:C	R245G	0.997
13:52148452:C:T	G189D	0.997
13:52148453:C:G	G189R	0.996
13:52148467:T:G	D184A	0.996
13:52148468:C:G	D184H	0.996
13:52151174:A:G	W174R	0.996
13:52151174:A:T	W174R	0.996
13:52152615:C:A	K129N	0.996
13:52152615:C:G	K129N	0.996
13:52152625:C:A	R126I	0.996
13:52148467:T:A	D184V	0.995
13:52148467:T:C	D184G	0.995
13:52148468:C:A	D184Y	0.995
13:52151351:G:C	D145E	0.995
13:52151351:G:T	D145E	0.995
13:52152617:T:C	K129E	0.995
13:52152622:T:G	D127A	0.995
13:52152631:A:G	L124P	0.995
13:52156093:T:A	K33N	0.995
13:52156093:T:G	K33N	0.995
13:52144866:A:G	L210P	0.994
13:52144889:A:C	F202L	0.994
13:52144889:A:T	F202L	0.994
13:52144891:A:G	F202L	0.994
13:52148460:C:A	W186C	0.994
13:52148460:C:G	W186C	0.994
13:52152622:T:A	D127V	0.994

dbSNP variants (sampled 300 via entrez): RS1000039486 (13:52142548 T>C), RS1000114793 (13:52154915 C>T), RS1000236892 (13:52155732 A>G), RS1000283031 (13:52161150 C>T), RS1000393556 (13:52148630 T>C), RS1000399658 (13:52161511 A>G), RS1000472036 (13:52155490 A>T), RS1000548775 (13:52137572 A>T), RS1000559435 (13:52142961 T>A,C), RS1000677643 (13:52147372 C>T), RS1000926591 (13:52150659 T>C), RS1001110249 (13:52160194 A>G), RS1001132205 (13:52147057 C>A,T), RS1001337266 (13:52136147 G>A), RS1001359013 (13:52143683 T>A)

Disease associations

OMIM: gene MIM:604044 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524130 (PROTEIN FAMILY), CHEMBL5679 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,169 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL513909	BI-2536	2	895
CHEMBL564829	MILCICLIB	2	821
CHEMBL587723	AEE-788	2	2,697
CHEMBL1908397	KW-2449	1	622
CHEMBL3545328	XL-019	1	715
CHEMBL482967	CYC-116	1	651

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 25 [PMID: 17935989]	Inhibition	5.78	pKi

ChEMBL bioactivities

26 potent at pChembl≥5 of 33 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	170	nM	R-406
6.61	IC50	245	nM	CHEMBL5575113
6.54	Kd	286	nM	MOMELOTINIB
6.45	Kd	353	nM	XL-019
6.19	Kd	640	nM	FEDRATINIB
6.14	Kd	720	nM	BI-2536
6.08	Kd	837	nM	ADAVOSERTIB
6.08	Kd	830	nM	CYC-116
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	KW-2449
5.96	Kd	1105	nM	Cerdulatinib Hydrochloride
5.96	Kd	1100	nM	RUXOLITINIB
5.69	Kd	2055	nM	AT-9283
5.62	Kd	2390	nM	MILCICLIB
5.62	Kd	2400	nM	NERATINIB
5.55	Kd	2840	nM	GILTERITINIB
5.53	Kd	2965	nM	VOLASERTIB
5.45	Kd	3569	nM	CHEMBL3752910
5.38	ED50	4176	nM	CHEMBL3752910
5.06	Kd	8800	nM	TAE-684
5.04	Kd	9120	nM	CHEMBL5653589

PubChem BioAssay actives

25 with measured affinity, of 819 total; 20 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
Momelotinib	1948824: Inhibition of NEK3 (unknown origin) assessed as dissociation constant	kd	0.1000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	1948824: Inhibition of NEK3 (unknown origin) assessed as dissociation constant	kd	0.1700	uM
N-propan-2-yl-4-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]benzamide	2095012: Inhibition of NEK3 (unknown origin) in presence of ATP	ic50	0.2450	uM
N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3530	uM
Fedratinib	1948824: Inhibition of NEK3 (unknown origin) assessed as dissociation constant	kd	0.6400	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624870: Binding constant for NEK3 kinase domain	kd	0.7200	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.8300	uM
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.8370	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1948824: Inhibition of NEK3 (unknown origin) assessed as dissociation constant	kd	1.0000	uM
Ruxolitinib	624870: Binding constant for NEK3 kinase domain	kd	1.1000	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1050	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.0550	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.3900	uM
Neratinib	624870: Binding constant for NEK3 kinase domain	kd	2.4000	uM
Gilteritinib	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.8400	uM
N-[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-4-[[(7R)-7-ethyl-5-methyl-6-oxo-8-propan-2-yl-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.9650	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148862: Binding affinity to human NEK3 incubated for 45 mins by Kinobead based pull down assay	kd	3.5690	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624870: Binding constant for NEK3 kinase domain	kd	8.8000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148862: Binding affinity to human NEK3 incubated for 45 mins by Kinobead based pull down assay	kd	9.1204	uM
6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1425087: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	38.0880	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
chromium hexavalent ion	decreases expression, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
zinc chromate	decreases expression, increases abundance	1
cadmium sulfate	decreases expression	1
methacrylaldehyde	increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, increases expression	1
Arsenates	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Cadmium	increases abundance, decreases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Succimer	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Naled	affects expression	1
Ozone	affects cotreatment, increases expression	1
Phthalic Acids	decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

170 unique, capped per target: 170 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4887137	Binding	NEK Invitrogen kinase activity assay	Data for DCP probe PF-04554878

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TA37	HAP1 NEK3 (-) 1	Cancer cell line	Male
CVCL_TA38	HAP1 NEK3 (-) 2	Cancer cell line	Male
CVCL_TA39	HAP1 NEK3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome