NEK9

Summary

NEK9 (NIMA related kinase 9, HGNC:18591) is a protein-coding gene on chromosome 14q24.3, encoding Serine/threonine-protein kinase Nek9 (Q8TD19). Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation.

This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein is activated in mitosis and, in turn, activates other family members during mitosis. This protein also mediates cellular processes that are essential for interphase progression.

Source: NCBI Gene 91754 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal-hepatic-pancreatic dysplasia 2 (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 709 total — 27 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_033116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18591
Approved symbol	NEK9
Name	NIMA related kinase 9
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Nek8, NERCC, DKFZp434D0935, MGC16714, NERCC1
Ensembl gene	ENSG00000119638
Ensembl biotype	protein_coding
OMIM	609798
Entrez	91754

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 9 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000238616, ENST00000553823, ENST00000553945, ENST00000554258, ENST00000555405, ENST00000555537, ENST00000555763, ENST00000555961, ENST00000556170, ENST00000557026, ENST00000557673, ENST00000676476, ENST00000676711, ENST00000677411, ENST00000677700, ENST00000678037, ENST00000678531, ENST00000678749, ENST00000909799, ENST00000909800, ENST00000909801, ENST00000944755

RefSeq mRNA: 3 — MANE Select: NM_033116 NM_001329237, NM_001329238, NM_033116

CCDS: CCDS91907, CCDS91908, CCDS9839

Canonical transcript exons

ENST00000238616 — 22 exons

Exon	Start	End
ENSE00001152093	75105950	75105996
ENSE00001285145	75126703	75127048
ENSE00001285173	75106502	75106702
ENSE00002455950	75079353	75084686
ENSE00003462011	75113339	75113403
ENSE00003468937	75109685	75109877
ENSE00003509152	75114203	75114313
ENSE00003512254	75117195	75117326
ENSE00003537424	75091270	75091478
ENSE00003568773	75107343	75107487
ENSE00003577958	75095372	75095431
ENSE00003584732	75100992	75101153
ENSE00003611655	75124046	75124223
ENSE00003627710	75097100	75097270
ENSE00003629267	75103842	75103997
ENSE00003633393	75101657	75101765
ENSE00003640678	75118830	75118935
ENSE00003648054	75121119	75121174
ENSE00003649189	75110321	75110371
ENSE00003672060	75120510	75120580
ENSE00003683187	75088480	75088641
ENSE00003689571	75087018	75087230

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5107 / max 169.1686, expressed in 1803 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144101	22.5107	1803

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	96.26	gold quality
right uterine tube	UBERON:0001302	96.00	gold quality
left ovary	UBERON:0002119	95.93	gold quality
tendon of biceps brachii	UBERON:0008188	95.84	gold quality
right ovary	UBERON:0002118	95.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.71	gold quality
lower esophagus	UBERON:0013473	95.70	gold quality
body of uterus	UBERON:0009853	95.50	gold quality
endocervix	UBERON:0000458	95.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.44	gold quality
gastrocnemius	UBERON:0001388	95.29	gold quality
ovary	UBERON:0000992	95.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.19	gold quality
stromal cell of endometrium	CL:0002255	95.16	gold quality
mucosa of stomach	UBERON:0001199	95.08	gold quality
muscle of leg	UBERON:0001383	95.06	gold quality
right adrenal gland cortex	UBERON:0035827	95.04	gold quality
right atrium auricular region	UBERON:0006631	95.01	gold quality
germinal epithelium of ovary	UBERON:0001304	94.80	gold quality
right adrenal gland	UBERON:0001233	94.77	gold quality
left uterine tube	UBERON:0001303	94.70	gold quality
apex of heart	UBERON:0002098	94.68	gold quality
cardiac atrium	UBERON:0002081	94.67	gold quality
tibial nerve	UBERON:0001323	94.55	gold quality
right coronary artery	UBERON:0001625	94.50	gold quality
right lobe of thyroid gland	UBERON:0001119	94.32	gold quality
parietal pleura	UBERON:0002400	94.30	gold quality
ectocervix	UBERON:0012249	94.28	gold quality
left adrenal gland	UBERON:0001234	94.27	gold quality
heart left ventricle	UBERON:0002084	94.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.57
E-MTAB-7249	no	128.32
E-CURD-112	no	2.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

138 targeting NEK9, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
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-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-106B-5P	99.88	74.72	2795

Literature-anchored findings (GeneRIF, showing 28)

• binds the Ran GTPase and regulates mitotic progression (PMID:12101123)
• Activated in mitosis, and activates nek6 and nek7 kinase. (PMID:12840024)
• mediates certain cellular processes, which are ultimately essential for interphase progression (PMID:14660563)
• The disruption of a nuclear function of NEK9 by adenovirus E1A-associated cellular proteins is reported. (PMID:17443675)
• The activity of Nek6 and Nek7, but not the tyrosine mutant, is increased by interaction with the Nek9 noncatalytic C-terminal domain, suggesting a mechanism in which the tyrosine is released from its autoinhibitory position. (PMID:19941817)
• DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. (PMID:21454704)
• Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. (PMID:21642957)
• The interaction between the human NimA-like protein kinase Nek9 and the Helicobacter HcpC has been validated by ELISA and surface plasmon resonance. (PMID:21735226)
• Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of gamma-tubulin to the centrosome in mitotic cells. (PMID:22818914)
• Structural analysis of LC8 with both Nek9 peptides, together with different biophysical experiments, explains the observed diminished binding affinity of Nek9 to LC8 upon phosphorylation on Ser(944) within the Nek9 sequence (PMID:23482567)
• NEK9 inhibition represents a novel anti-cancer strategy by induction of mitotic catastrophe via impairment of spindle dynamics, cytokinesis and mitotic checkpoint control. (PMID:23665325)
• The findings demonstrate that a novel NEK9 network regulates the growth of cancer cells lacking functional p53. (PMID:25131192)
• The C-terminal domain of Nek9 activates Nek7 through promoting back-to-back dimerization. (PMID:26522158)
• Overall, these results highlight the complexity of virus-host interactions and identify a new role for the cellular protein Nek9 during human adenovirus infection, suggesting a role for Nek9 in regulating p53 target gene expression. (PMID:26676776)
• Recessive NEK9 mutation is associated with lethal skeletal dysplasia. (PMID:26908619)
• High expression level of NEK9 is associated with recurrence in glioblastoma. (PMID:26956052)
• Somatic Mutations in NEK9 Cause Nevus Comedonicus. (PMID:27153399)
• Signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14 to properly coordinate cytokinesis. (PMID:28630147)
• Eg5 localization and centrosome separation in prophase depend on the nuclear microtubule-associated protein TPX2, a pool of which localizes to the centrosomes before nuclear envelope breakdown. This localization involves the kinase Nek9, which phosphorylates TPX2 nuclear localization signal preventing its interaction with importin and nuclear import. (PMID:29276125)
• This study supports a role for NEK9 and MAP2K4 in mediating buparlisib resistance and demonstrates the value of unbiased omic analyses in uncovering resistance mechanisms to targeted therapy in Triple-Negative Breast Cancers. (PMID:29472518)
• NIMA-related kinase 9-mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1. (PMID:31857374)
• Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer. (PMID:32098687)
• EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7. (PMID:32184261)
• NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation. (PMID:33500736)
• The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer. (PMID:33664869)
• Three novel pathogenic NEK9 variants in patients with nevus comedonicus: A case series. (PMID:33819539)
• Study on the Expression of lncRNA ATB and Nek9 in Breast Cancer Patients Based on Q-PCR Technology and Its Relationship with the Disease. (PMID:35935324)
• NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart. (PMID:36266340)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nek9	ENSMUSG00000034290
rattus_norvegicus	Nek9	ENSRNOG00000058572
drosophila_melanogaster	niki	FBGN0045980

Paralogs (8): NEK11 (ENSG00000114670), NEK2 (ENSG00000117650), NEK6 (ENSG00000119408), NEK3 (ENSG00000136098), NEK7 (ENSG00000151414), NEK8 (ENSG00000160602), NEK10 (ENSG00000163491), NEK5 (ENSG00000197168)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek9 — Q8TD19 (reviewed: Q8TD19)

Alternative names: Nercc1 kinase, Never in mitosis A-related kinase 9, NimA-related kinase 8

All UniProt accessions (8): Q8TD19, A0A7I2V454, A0A7I2V4E9, A0A7I2V5R1, G3V2Z5, G3V459, G3V5V0, G3V5V6

UniProt curated annotations — full annotation on UniProt →

Function. Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues. Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively.

Subunit / interactions. Homodimer; homodimerization is required to activate NEK7. Binds to Ran GTPase. Has a greater affinity for Ran-GDP over Ran-GTP. Interacts with SSRP1 and SUPT16H, the 2 subunits of the FACT complex. Interacts with DYNLL1; phosphorylation at Ser-944 strongly reduces DYNLL1 binding.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Most abundant in heart, liver, kidney and testis. Also expressed in smooth muscle cells and fibroblasts.

Post-translational modifications. Autophosphorylated on serine and threonine residues. When complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210. During mitosis, not phosphorylated on Thr-210. Phosphorylated by CDK1 in vitro.

Disease relevance. Lethal congenital contracture syndrome 10 (LCCS10) [MIM:617022] A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. The disease is caused by variants affecting the gene represented in this entry. Nevus comedonicus (NC) [MIM:617025] A rare type of epidermal nevus characterized by closely arranged, dilated, plugged follicular ostia in a honeycomb pattern. The plugged ostia contain lamellated keratinaceous material, and their appearance resembles black dots. NC may be non-pyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Most commonly it affects the face and neck area and, by exception, other anatomical regions, including genital area, palms, and soles. NC lesions might present with various patterns of distribution: unilateral, bilateral, linear, interrupted, segmental, or blaschkoid. The disease is caused by variants affecting the gene represented in this entry. Arthrogryposis, Perthes disease, and upward gaze palsy (APUG) [MIM:614262] An autosomal recessive, syndromic form of arthrogryposis, a disease characterized by persistent joints flexure or contracture. APUG patients manifest an unusual combination of arthrogryposis, upward gaze palsy, and avascular necrosis of the hip (Perthes disease). The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated during mitosis by intramolecular autophosphorylation. Activity and autophosphorylation is activated by manganese » magnesium ions. Sensitive to increasing concentration of detergents. It is not cell-cycle regulated but activity is higher in G0-arrested cells.

Domain organisation. Dimerizes through its coiled-coil domain.

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

RefSeq proteins (3): NP_001316166, NP_001316167, NP_149107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000408	Reg_chr_condens	Repeat
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR042767	Nek9_STKc	Domain
IPR051997	STK_NEK	Family
IPR058923	RCC1-like_dom	Domain

Pfam: PF00069, PF25390

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 (52 total): modified residue 20, repeat 6, sequence variant 6, region of interest 5, mutagenesis site 3, compositionally biased region 2, binding site 2, sequence conflict 2, initiator methionine 1, chain 1, coiled-coil region 1, active site 1, domain 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3ZKE	X-RAY DIFFRACTION	2.2
3ZKF	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD19-F1	75.18	0.45

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): 176 (proton acceptor)

Ligand- & substrate-binding residues (2): 58–66; 81

Post-translational modifications (20): 2, 2, 13, 16, 20, 29, 52, 76, 210, 254, 331, 333, 741, 801, 832, 868, 869, 886, 944, 978

Mutagenesis-validated functional residues (3):

Position	Phenotype
81	loss of activity and autophosphorylation.
210	significant reduction of autophosphorylation.
214	no effect on autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-2980767	Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-1640170	Cell Cycle
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-68875	Mitotic Prophase
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 584 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_ATRX, GOBP_HIPPO_SIGNALING, chr17q11, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SPECIFICATION_OF_SYMMETRY, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, chr14q24, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, AGGAGTG_MIR483, TGANTCA_AP1_C

GO Biological Process (5): mitotic cell cycle (GO:0000278), regulation of mitotic cell cycle (GO:0007346), cell division (GO:0051301), protein phosphorylation (GO:0006468), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein kinase binding (GO:0019901), protein kinase activator activity (GO:0030295), 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), cytosol (GO:0005829), cytoplasm (GO:0005737), centrosome (GO:0005813)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Nuclear Envelope Breakdown	2
M Phase	2
Mitotic Prometaphase	1
Mitotic Prophase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
mitotic cell cycle	1
regulation of cell cycle	1
cellular process	1
phosphorylation	1
protein modification process	1
positive regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
positive regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase binding	1
kinase activator activity	1
protein kinase regulator activity	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
cytoplasm	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

2010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK9	ANKS6	Q68DC2	980
NEK9	NPHP3	Q7Z494	973
NEK9	NEK7	Q8TDX7	950
NEK9	INVS	Q9Y283	928
NEK9	BICD2	Q8TD16	875
NEK9	ANKS3	Q6ZW76	759
NEK9	PKD2	Q13563	698
NEK9	PKD1	P98161	697
NEK9	SRI	P30626	693
NEK9	NPHP4	O75161	676
NEK9	GABARAPL2	P60520	655
NEK9	F5GZY7	F5GZY7	655
NEK9	CSN2	P05814	651
NEK9	REC114	Q7Z4M0	641
NEK9	NEDD1	Q8NHV4	610

IntAct

141 interactions, top by confidence:

A	B	Type	Score
PAK4	YWHAZ	psi-mi:“MI:0914”(association)	0.920
NEK9	DYNLL1	psi-mi:“MI:0915”(physical association)	0.900
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
NEK9	DYNLL1	psi-mi:“MI:0914”(association)	0.900
NEK6	NEK9	psi-mi:“MI:0914”(association)	0.780
NEK6	NEK9	psi-mi:“MI:0915”(physical association)	0.780
FAM9C	SNAP29	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
NEK7	ANKS6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NEK9	GABARAPL2	psi-mi:“MI:0407”(direct interaction)	0.700
GABARAPL2	NEK9	psi-mi:“MI:0915”(physical association)	0.700
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
rep	MTHFD1	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
PLK1	NEK9	psi-mi:“MI:0915”(physical association)	0.630
NEK9	PLK1	psi-mi:“MI:0915”(physical association)	0.630

BioGRID (190): NEK9 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), NEK9 (Affinity Capture-MS), NEK9 (Affinity Capture-MS), NEK9 (Affinity Capture-MS), CSN2 (Biochemical Activity), NEK8 (Biochemical Activity), BICD2 (Biochemical Activity), NEK9 (Affinity Capture-Western), BICD2 (Affinity Capture-Western), NEK9 (Proximity Label-MS), NEK9 (Affinity Capture-MS), NEK9 (Affinity Capture-MS), NEK9 (Affinity Capture-MS), NEK9 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RPR8, A0A7N9VSG0, D3ZGQ5, D3ZHP7, O08644, O09127, O15197, O43542, O73875, O73878, O75676, P0C0K6, P0C0K7, P21709, P23800, P29317, P29322, P41243, P51839, P51840, P52785, P54753, P54754, P54760, P54761, P55203, P57078, P97343, Q1KL86, Q3U3Q1, Q4V7Q6, Q5RCY1, Q5ZJH6, Q60750, Q62270, Q63285, Q6PHR2, Q7ZZC8, Q80YD6, Q86SG6

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

10 interactions.

A	Effect	B	Mechanism
NEK9	“up-regulates activity”	NEK6	phosphorylation
NEK9	“up-regulates activity”	NEK7	phosphorylation
NEK9	up-regulates	NEK9	phosphorylation
dabrafenib	“down-regulates activity”	NEK9	“chemical inhibition”
PLK1	“up-regulates activity”	NEK9	phosphorylation
CDK1	“up-regulates activity”	NEK9	phosphorylation
NEK9	“up-regulates activity”	ARHGEF2	phosphorylation
NEK9	“up-regulates activity”	NEDD1	phosphorylation
NEK9	“down-regulates activity”	MAP1LC3B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	37.7×	4e-05
Macroautophagy	10	13.0×	2e-06
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	10.9×	5e-03
AURKA Activation by TPX2	6	10.3×	2e-03
Loss of Nlp from mitotic centrosomes	5	8.9×	8e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	8.9×	8e-03
Regulation of PLK1 Activity at G2/M Transition	6	8.6×	4e-03
Autophagy	5	8.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	7	21.2×	1e-05
mitophagy	7	19.2×	2e-05
autophagosome assembly	8	15.5×	1e-05
mitotic spindle organization	6	14.1×	7e-04
cellular response to starvation	6	10.0×	4e-03
protein phosphorylation	9	5.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	31
Uncertain significance	409
Likely benign	131
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1177403	NM_178170.3(NEK8):c.515dup (p.Pro172_Glu173insTer)	Pathogenic
1413416	NM_178170.3(NEK8):c.1997dup (p.Tyr666Ter)	Pathogenic
1426313	NM_178170.3(NEK8):c.882_885del (p.Cys295fs)	Pathogenic
1488	NM_178170.3(NEK8):c.1273C>T (p.His425Tyr)	Pathogenic
1686761	NM_033116.6(NEK9):c.1843C>T (p.Arg615Ter)	Pathogenic
2053489	NM_178170.3(NEK8):c.1924C>T (p.Arg642Ter)	Pathogenic
2054772	NM_033116.6(NEK9):c.1033C>T (p.Arg345Ter)	Pathogenic
2060841	NM_033116.6(NEK9):c.1794dup (p.Ile599fs)	Pathogenic
2138572	NM_033116.6(NEK9):c.1934del (p.Gly645fs)	Pathogenic
2308656	NM_033116.6(NEK9):c.2239C>T (p.Gln747Ter)	Pathogenic
242929	NM_033116.6(NEK9):c.1489C>T (p.Arg497Ter)	Pathogenic
242988	NM_033116.4(NEK9):c.1817T>C (p.Ile573Thr)	Pathogenic
243002	NM_033116.6(NEK9):c.500T>C (p.Ile167Thr)	Pathogenic
3256606	NEK8, ARG45TRP	Pathogenic
3256607	K157Q	Pathogenic
373375	NM_033116.6(NEK9):c.727G>T (p.Glu243Ter)	Pathogenic
3878766	NM_178170.3(NEK8):c.67C>T (p.Arg23Ter)	Pathogenic
4277741	NM_033116.6(NEK9):c.2801T>G (p.Leu934Ter)	Pathogenic
4717277	NM_178170.3(NEK8):c.1395del (p.Phe465fs)	Pathogenic
471779	NM_178170.3(NEK8):c.743del (p.Pro248fs)	Pathogenic
490179	NM_178170.3(NEK8):c.259A>G (p.Thr87Ala)	Pathogenic
490181	NM_178170.3(NEK8):c.1738G>A (p.Gly580Ser)	Pathogenic
490182	NM_178170.3(NEK8):c.47+1G>A	Pathogenic
490183	NM_178170.3(NEK8):c.379C>T (p.Arg127Ter)	Pathogenic
490184	NM_178170.3(NEK8):c.1384C>T (p.Arg462Ter)	Pathogenic
503832	NM_178170.3(NEK8):c.238del (p.Met80fs)	Pathogenic
987459	NM_033116.6(NEK9):c.1432del (p.Leu478fs)	Pathogenic
1031033	NM_033116.6(NEK9):c.1327+1G>T	Likely pathogenic
1299543	NM_033116.6(NEK9):c.219G>C (p.Glu73Asp)	Likely pathogenic
1299544	NM_033116.6(NEK9):c.2101C>T (p.Arg701Trp)	Likely pathogenic

SpliceAI

3505 predictions. Top by Δscore:

Variant	Effect	Δscore
14:75087231:C:CC	acceptor_gain	1.0000
14:75097267:TTAT:T	acceptor_gain	1.0000
14:75100988:TCA:T	donor_loss	1.0000
14:75100989:CA:C	donor_loss	1.0000
14:75100990:A:AC	donor_gain	1.0000
14:75100991:C:CC	donor_gain	1.0000
14:75100991:C:CT	donor_loss	1.0000
14:75100991:CCAT:C	donor_gain	1.0000
14:75101149:TCGCT:T	acceptor_gain	1.0000
14:75101150:CGCT:C	acceptor_gain	1.0000
14:75101150:CGCTC:C	acceptor_gain	1.0000
14:75101152:CT:C	acceptor_gain	1.0000
14:75101152:CTCTG:C	acceptor_loss	1.0000
14:75101153:TCTG:T	acceptor_gain	1.0000
14:75101154:C:A	acceptor_loss	1.0000
14:75101154:C:CC	acceptor_gain	1.0000
14:75101154:C:G	acceptor_gain	1.0000
14:75101155:T:A	acceptor_loss	1.0000
14:75101166:C:CT	acceptor_gain	1.0000
14:75101167:A:T	acceptor_gain	1.0000
14:75101650:AACTT:A	donor_loss	1.0000
14:75101651:ACTTA:A	donor_loss	1.0000
14:75101652:CTTA:C	donor_loss	1.0000
14:75101653:TTAC:T	donor_loss	1.0000
14:75101654:TACC:T	donor_loss	1.0000
14:75101655:A:AC	donor_gain	1.0000
14:75101655:AC:A	donor_gain	1.0000
14:75101655:ACCA:A	donor_loss	1.0000
14:75101655:ACCAT:A	donor_gain	1.0000
14:75101656:C:CG	donor_gain	1.0000

AlphaMissense

6366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:75097250:C:G	G675R	1.000
14:75097253:A:G	W674R	1.000
14:75097253:A:T	W674R	1.000
14:75106520:A:G	W504R	1.000
14:75106520:A:T	W504R	1.000
14:75106678:C:T	G451E	1.000
14:75109690:A:G	W393R	1.000
14:75109690:A:T	W393R	1.000
14:75109813:A:G	W352R	1.000
14:75109813:A:T	W352R	1.000
14:75113389:T:A	R296S	1.000
14:75113389:T:G	R296S	1.000
14:75113390:C:G	R296T	1.000
14:75114298:A:G	C260R	1.000
14:75114300:A:G	L259P	1.000
14:75114306:A:G	L257P	1.000
14:75114306:A:T	L257H	1.000
14:75117204:A:C	F251L	1.000
14:75117204:A:T	F251L	1.000
14:75117205:A:G	F251S	1.000
14:75117206:A:G	F251L	1.000
14:75117229:T:A	E243V	1.000
14:75117240:G:C	C239W	1.000
14:75117241:C:T	C239Y	1.000
14:75117242:A:G	C239R	1.000
14:75117244:C:T	G238D	1.000
14:75117245:C:G	G238R	1.000
14:75117251:C:G	A236P	1.000
14:75117252:C:A	W235C	1.000
14:75117252:C:G	W235C	1.000

dbSNP variants (sampled 300 via entrez): RS1000037342 (14:75081076 T>C), RS1000117199 (14:75123412 A>G), RS1000252715 (14:75084077 C>A,T), RS1000264766 (14:75127348 A>G), RS1000365757 (14:75097180 G>A), RS1000406053 (14:75080544 T>C), RS1000563745 (14:75128174 A>C,G), RS1000618655 (14:75100549 A>G), RS1000631669 (14:75082848 C>G), RS1000664023 (14:75114680 T>C), RS1000686640 (14:75078954 G>C), RS1000703125 (14:75087645 G>A,C,T), RS1000707973 (14:75084425 G>A), RS1000725175 (14:75107565 C>T), RS1000738359 (14:75079319 G>GA)

Disease associations

OMIM: gene MIM:609798 | disease phenotypes: MIM:613824, MIM:615415, MIM:620903, MIM:614262, MIM:617022, MIM:609460, MIM:617025

GenCC curated gene-disease

Disease	Classification	Inheritance
renal-hepatic-pancreatic dysplasia 2	Definitive	Autosomal recessive
NEK9-related lethal skeletal dysplasia	Strong	Autosomal recessive
nephronophthisis 9	Strong	Autosomal recessive
polycystic kidney disease 8	Moderate	Autosomal dominant
renal-hepatic-pancreatic dysplasia	Supportive	Autosomal recessive
nephronophthisis 2	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Strong	AD
renal-hepatic-pancreatic dysplasia 2	Definitive	AR

Mondo (18): nephronophthisis 9 (MONDO:0013444), renal-hepatic-pancreatic dysplasia 2 (MONDO:0014174), polycystic kidney disease 8 (MONDO:0971178), arthrogryposis, Perthes disease, and upward gaze palsy (MONDO:0013660), NEK9-related lethal skeletal dysplasia (MONDO:0014870), Goldberg-Shprintzen syndrome (MONDO:0012280), prostate cancer (MONDO:0008315), omphalocele (MONDO:0019015), congenital contractures (MONDO:0022823), kidney disorder (MONDO:0005240), nevus comedonicus syndrome (MONDO:0014873), kidney failure (MONDO:0001106), familial cystic renal disease (MONDO:0019741), premature menopause (MONDO:0001119), retinal disorder (MONDO:0005283)

Orphanet (8): Nephronophthisis (Orphanet:655), NEK9-related lethal skeletal dysplasia (Orphanet:464366), Goldberg-Shprintzen megacolon syndrome (Orphanet:66629), Familial prostate cancer (Orphanet:1331), Omphalocele (Orphanet:660), Nevus comedonicus syndrome (Orphanet:64754), Genetic cystic renal disease (Orphanet:93587), Cleft palate (Orphanet:2014)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000293	Full cheeks
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000470	Short neck
HP:0000473	Torticollis
HP:0000494	Downslanted palpebral fissures
HP:0000518	Cataract
HP:0000774	Narrow chest
HP:0000778	Hypoplasia of the thymus
HP:0000885	Broad ribs
HP:0001047	Atopic dermatitis
HP:0001052	Nevus flammeus
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001442	Typified by somatic mosaicism
HP:0001511	Intrauterine growth retardation
HP:0001539	Omphalocele
HP:0001562	Oligohydramnios
HP:0001595	Abnormal hair morphology
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001640	Cardiomegaly
HP:0001642	Pulmonic stenosis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004622_47	Reticulocyte count	2.000000e-10
GCST005195_23	Coronary artery disease	4.000000e-10
GCST005196_5	Coronary artery disease	4.000000e-10
GCST006947_16	Feeling fed-up	1.000000e-09
GCST90002406_453	Reticulocyte fraction of red cells	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009588	feeling “fed-up” measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
D012164	Retinal Diseases	C11.768
C537279	Goldberg-Shprintzen megacolon syndrome (supp.)
C566582	Nephronophthisis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524130 (PROTEIN FAMILY), CHEMBL5257 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 60,602 (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
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL482968	ENMD-2076	2	1,656
CHEMBL495727	AT-9283	2	1,376
CHEMBL564829	MILCICLIB	2	821
CHEMBL575448	BMS-754807	2	406
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1908397	KW-2449	1	622
CHEMBL3545328	XL-019	1	715
CHEMBL482967	CYC-116	1	651
CHEMBL574738	AST-487	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

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM

ChEMBL bioactivities

48 potent at pChembl≥5 of 49 total, top 41 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.80	Kd	16	nM	R-406
7.64	Kd	22.91	nM	CHEMBL5653589
7.39	Kd	41	nM	FOSTAMATINIB
7.28	Kd	53	nM	DABRAFENIB
7.28	ED50	51.94	nM	CHEMBL5653589
7.15	IC50	71	nM	STAUROSPORINE
7.14	Kd	71.81	nM	CHEMBL3752910
7.03	IC50	92.7	nM	STAUROSPORINE
7.00	IC50	100	nM	MOMELOTINIB
6.88	Kd	133	nM	CYC-116
6.88	IC50	131	nM	STAUROSPORINE
6.82	Kd	150	nM	FEDRATINIB
6.79	ED50	162.8	nM	CHEMBL3752910
6.75	Kd	180	nM	R-406
6.42	Kd	380	nM	CHEMBL3763358
6.33	Kd	470	nM	FORETINIB
6.32	Kd	474	nM	MOMELOTINIB
6.28	Kd	520	nM	KW-2449
6.22	IC50	600	nM	REBASTINIB
6.18	Kd	654	nM	BMS-754807
6.10	Kd	790	nM	CRIZOTINIB
6.10	Kd	800	nM	TAE-684
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	GSK-461364
5.83	Kd	1492	nM	KW-2449
5.82	Kd	1532	nM	AT-9283
5.79	Kd	1634	nM	FEDRATINIB
5.75	Kd	1780	nM	PACRITINIB
5.75	Kd	1800	nM	AST-487
5.74	IC50	1803	nM	CHEMBL4793380
5.69	Kd	2051	nM	DOVITINIB
5.69	Kd	2034	nM	DANUSERTIB
5.66	Kd	2186	nM	XL-019
5.53	Kd	2977	nM	ENMD-2076
5.51	Kd	3100	nM	STAUROSPORINE
5.27	Kd	5400	nM	LESTAURTINIB
5.17	Kd	6700	nM	STAUROSPORINE
5.04	Kd	9100	nM	DOVITINIB
5.00	Kd	1e+04	nM	BMS-754807

PubChem BioAssay actives

46 with measured affinity, of 714 total; 27 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
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	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.0160	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148864: Binding affinity to human NEK9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0229	uM
Fostamatinib	1425089: 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	0.0410	uM
Dabrafenib	1425089: 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	0.0530	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715240: Inhibition of human NEK9 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0710	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148864: Binding affinity to human NEK9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0718	uM
Momelotinib	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.1000	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425089: 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	0.1330	uM
Fedratinib	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.1500	uM
2-[7-methoxy-6-(2-methoxyethoxy)quinazolin-4-yl]-5-pyridin-2-yl-1,2,4-triazol-3-amine	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.3800	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.4700	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	0.5200	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168251: Inhibition of human wild type NEK9 using RBER-GSK3(14 to 27) as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.6000	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	1425089: 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	0.6540	uM
Crizotinib	624704: Binding constant for NEK9 kinase domain	kd	0.7900	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	624704: Binding constant for NEK9 kinase domain	kd	0.8000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	624704: Binding constant for NEK9 kinase domain	kd	1.1000	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1425089: 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	1.5320	uM
Pacritinib	1425089: 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	1.7800	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	1948829: Inhibition of NEK9 (unknown origin) assessed as dissociation constant	kd	1.8000	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735634: Inhibition of recombinant human NEK9 (1 to 324 residues) using myelin basic protein as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	1.8030	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425089: 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	2.0340	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	1425089: 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	2.0510	uM
N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide	1425089: 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	2.1860	uM
6-(4-methylpiperazin-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(E)-2-phenylethenyl]pyrimidin-4-amine	1425089: 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	2.9770	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	624704: Binding constant for NEK9 kinase domain	kd	5.4000	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1425089: 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	19.6170	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	3
Acetaminophen	increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Manganese	decreases expression, affects cotreatment, increases abundance	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	decreases expression	1

ChEMBL screening assays

254 unique, capped per target: 254 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CH	Abcam A-431 NEK9 KO	Cancer cell line	Female
CVCL_TA49	HAP1 NEK9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer