NEK11

Summary

NEK11 (NIMA related kinase 11, HGNC:18593) is a protein-coding gene on chromosome 3q22.1, encoding Serine/threonine-protein kinase Nek11 (Q8NG66). Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage.

This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 79858 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 123 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18593
Approved symbol	NEK11
Name	NIMA related kinase 11
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23495
Ensembl gene	ENSG00000114670
Ensembl biotype	protein_coding
OMIM	609779
Entrez	79858

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 25 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay, 1 non_stop_decay

ENST00000356918, ENST00000383366, ENST00000426022, ENST00000506695, ENST00000507910, ENST00000507967, ENST00000508196, ENST00000510474, ENST00000510688, ENST00000510769, ENST00000510823, ENST00000510926, ENST00000511262, ENST00000513550, ENST00000514915, ENST00000515636, ENST00000602792, ENST00000851273, ENST00000851274, ENST00000851275, ENST00000851276, ENST00000851277, ENST00000851278, ENST00000851279, ENST00000851280, ENST00000972124, ENST00000972125, ENST00000972126, ENST00000972127, ENST00000972128, ENST00000972129, ENST00000972130, ENST00000972131, ENST00000972132, ENST00000972133

RefSeq mRNA: 33 — MANE Select: NM_024800 NM_001146003, NM_001321220, NM_001321221, NM_001321222, NM_001321223, NM_001321224, NM_001353022, NM_001353023, NM_001353024, NM_001353025, NM_001353026, NM_001353027, NM_001353028, NM_001353029, NM_001353030, NM_001353031, NM_001353032, NM_001353033, NM_001353034, NM_001353036, NM_001353037, NM_001353038, NM_001353039, NM_001353040, NM_001353041, NM_001353042, NM_001353043, NM_001353044, NM_001353045, NM_001353046, NM_001353048, NM_024800, NM_145910

CCDS: CCDS3069, CCDS46915, CCDS54639, CCDS82836, CCDS82837

Canonical transcript exons

ENST00000383366 — 18 exons

Exon	Start	End
ENSE00001496416	131349557	131350465
ENSE00002087883	131027930	131028002
ENSE00003467077	131168830	131168937
ENSE00003486619	131170773	131170887
ENSE00003501183	131080423	131080588
ENSE00003515668	131155036	131155121
ENSE00003568527	131152631	131152709
ENSE00003568926	131228528	131228688
ENSE00003584694	131109803	131109921
ENSE00003599666	131273478	131273574
ENSE00003619739	131152388	131152537
ENSE00003645982	131029613	131029878
ENSE00003652420	131133830	131133956
ENSE00003666868	131243436	131243496
ENSE00003669816	131132745	131132809
ENSE00003675125	131162408	131162527
ENSE00003677625	131165426	131165519
ENSE00003842942	131026877	131027006

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 96.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5697 / max 64.2285, expressed in 1457 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38606	3.0283	1253
38607	1.5213	845
38609	0.0200	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.16	gold quality
bronchial epithelial cell	CL:0002328	95.22	gold quality
epithelium of bronchus	UBERON:0002031	94.19	gold quality
bronchus	UBERON:0002185	92.81	gold quality
choroid plexus epithelium	UBERON:0003911	90.48	gold quality
sperm	CL:0000019	89.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.78	gold quality
left testis	UBERON:0004533	87.04	gold quality
right testis	UBERON:0004534	86.98	gold quality
calcaneal tendon	UBERON:0003701	86.81	gold quality
male germ cell	CL:0000015	86.46	gold quality
tendon of biceps brachii	UBERON:0008188	85.69	gold quality
testis	UBERON:0000473	84.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.76	gold quality
tendon	UBERON:0000043	83.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.15	gold quality
ventricular zone	UBERON:0003053	82.14	gold quality
left lobe of thyroid gland	UBERON:0001120	80.36	gold quality
middle temporal gyrus	UBERON:0002771	80.29	gold quality
thyroid gland	UBERON:0002046	80.10	gold quality
right lobe of thyroid gland	UBERON:0001119	79.94	gold quality
epithelium of nasopharynx	UBERON:0001951	79.82	gold quality
anterior cingulate cortex	UBERON:0009835	79.71	gold quality
caudate nucleus	UBERON:0001873	79.64	gold quality
cingulate cortex	UBERON:0003027	79.61	gold quality
right adrenal gland cortex	UBERON:0035827	79.58	gold quality
right frontal lobe	UBERON:0002810	78.95	gold quality
right adrenal gland	UBERON:0001233	78.90	gold quality
adenohypophysis	UBERON:0002196	78.80	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.37
E-MTAB-6142	no	82.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6

miRNA regulators (miRDB)

28 targeting NEK11, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002
HSA-MIR-6800-5P	94.59	64.80	525

Literature-anchored findings (GeneRIF, showing 8)

• Nek11 has a role in the S-phase checkpoint downstream of the caffeine-sensitive pathway (PMID:12154088)
• Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells (PMID:15161910)
• NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. (PMID:19734889)
• NEK11 controls degradation of CDC25A by directly phosphorylating CDC25A on residues whose phosphorylation is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. (PMID:20090422)
• Results show that downregulation of NEK11 in drug resistant cells might contribute to drug resistance in ovarian cancer. (PMID:24969318)
• contributes to response of colorectal cancer cells to genotoxic agents and is essential for survival either with or without exposure to DNA damage (PMID:26501353)
• NEK11 as a candidate high-penetrance melanoma susceptibility gene. (PMID:31704778)
• Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children. (PMID:32034166)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nek11	ENSDARG00000087564
mus_musculus	Nek11	ENSMUSG00000035032
rattus_norvegicus	Nek11	ENSRNOG00000042432

Paralogs (8): NEK2 (ENSG00000117650), NEK6 (ENSG00000119408), NEK9 (ENSG00000119638), NEK3 (ENSG00000136098), NEK7 (ENSG00000151414), NEK8 (ENSG00000160602), NEK10 (ENSG00000163491), NEK5 (ENSG00000197168)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek11 — Q8NG66 (reviewed: Q8NG66)

Alternative names: Never in mitosis A-related kinase 11

All UniProt accessions (5): A0A075B7B3, D6RGV6, D6RJF7, E9PHI8, Q8NG66

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation.

Subunit / interactions. Interacts with isoform 1 of NEK2.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Poorly expressed in cerebellum, trachea, lung, appendix, and uterus.

Post-translational modifications. Phosphorylated by NEK2. Phosphorylation at Ser-273 is important for its activation.

Activity regulation. Autorepressed by intramolecular binding of the C-terminus which dissociates following phosphorylation by NEK2 isoform 1 in G1/S-arrested cells. NEK2 isoform 2 is largely not present in the nucleolus, and does not appear to phosphorylate NEK11. Activated in response to DNA damage. Inhibited by zinc.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NG66-1	1, Long	yes
Q8NG66-2	2, Short
Q8NG66-3	3
Q8NG66-4	4

RefSeq proteins (33): NP_001139475, NP_001308149, NP_001308150, NP_001308151, NP_001308152, NP_001308153, NP_001339951, NP_001339952, NP_001339953, NP_001339954, NP_001339955, NP_001339956, NP_001339957, NP_001339958, NP_001339959, NP_001339960, NP_001339961, NP_001339962, NP_001339963, NP_001339965, NP_001339966, NP_001339967, NP_001339968, NP_001339969, NP_001339970, NP_001339971, NP_001339972, NP_001339973, NP_001339974, NP_001339975, NP_001339977, NP_079076, NP_665917 (=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

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 11, splice variant 6, binding site 2, chain 1, domain 1, region of interest 1, mutagenesis site 1, coiled-coil region 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NG66-F1	68.84	0.26

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): 158 (proton acceptor)

Ligand- & substrate-binding residues (2): 35–43; 61

Post-translational modifications (1): 273

Mutagenesis-validated functional residues (1):

Position	Phenotype
61	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A

MSigDB gene sets: 110 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, MODULE_171, GOBP_REGULATION_OF_CELL_CYCLE, MODULE_301, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_DNA_INTEGRITY_CHECKPOINT_SIGNALING, GOBP_MITOTIC_CELL_CYCLE, GOBP_SIGNAL_TRANSDUCTION_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_CELL_CYCLE_CHECKPOINT_SIGNALING

GO Biological Process (4): protein phosphorylation (GO:0006468), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), intracellular signal transduction (GO:0035556), regulation of mitotic cell cycle phase transition (GO:1901990)

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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
p53-Independent G1/S DNA Damage Checkpoint	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
nuclear lumen	2
phosphorylation	1
protein modification process	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
intracellular anatomical structure	1
signal transduction	1
regulation of mitotic cell cycle	1
mitotic cell cycle phase transition	1
regulation of cell cycle phase transition	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
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK11	CROCC	Q5TZA2	675
NEK11	CEP250	Q9BV73	645
NEK11	CDC25A	P30304	525
NEK11	NEK1	Q96PY6	520
NEK11	NEK8	Q86SG6	466
NEK11	ATM	Q13315	464
NEK11	DOCK8	Q8NF50	438
NEK11	MFHAS1	Q9Y4C4	437
NEK11	NPM1	P06748	430
NEK11	MARCHF9	Q86YJ5	429
NEK11	IFFO1	Q0D2I5	415
NEK11	XRCC6	P12956	398
NEK11	H2BC21	Q16778	389
NEK11	H2AC20	Q16777	388
NEK11	H2AC19	P20670	387

IntAct

20 interactions, top by confidence:

A	B	Type	Score
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
HSP90AB1	NEK11	psi-mi:“MI:0915”(physical association)	0.560
NEK11	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
NEK11	NEK11	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
NEK11	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
NEK11	FKBP5	psi-mi:“MI:0915”(physical association)	0.400
NEK2	NEK11	psi-mi:“MI:0915”(physical association)	0.400
MYC	NEK11	psi-mi:“MI:0915”(physical association)	0.370
	AURKA	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
NEK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): BLM (Biochemical Activity), NEK11 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), NEK11 (Reconstituted Complex), NEK11 (Co-fractionation), NEK11 (Co-fractionation), NEK11 (Co-fractionation), NEK11 (Co-fractionation), VDAC3 (Co-fractionation), NEK11 (Proximity Label-MS), NEK11 (Proximity Label-MS), FKBP5 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), SFN (Affinity Capture-MS)

ESM2 similar proteins: A0JPN4, A4PES0, A4QNA8, D2HHP1, D4A7V9, E1BTE1, E2RSS3, O02776, O57473, O88622, O88866, P0C1S8, P47810, P47817, P54350, P57058, Q08D35, Q1LX29, Q1LX51, Q20443, Q2KIP2, Q63185, Q63802, Q66JT0, Q68UT7, Q6DFE0, Q6IRU7, Q6NVF4, Q6P1H6, Q6P1W0, Q6Z829, Q86W56, Q8AYG3, Q8AYK6, Q8BGE5, Q8BMI4, Q8C0Q4, Q8CFA1, Q8L4H0, Q8NG66

Diamond homologs: A0A078CGE6, A0QNG1, A5TY84, A5TY85, A5U3A3, A5U3A6, A6QGC0, B0BBT2, B3NE99, B4PDM5, O15530, O22971, O34507, O55173, P0A5S5, P0DPS8, P0DPS9, P33973, P49695, P51957, P54736, P54738, P54739, P54740, P54741, P54742, P54743, P54744, P65727, P65731, P65733, P9WI62, P9WI63, P9WI64, P9WI65, P9WI66, P9WI67, P9WI68, P9WI69, P9WI70

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NEK2	up-regulates	NEK11	phosphorylation
CHEK1	up-regulates	NEK11	phosphorylation
NEK11	down-regulates	CDC25A	phosphorylation
dabrafenib	“down-regulates activity”	NEK11	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4698 predictions. Top by Δscore:

Variant	Effect	Δscore
3:131080414:T:TA	acceptor_gain	1.0000
3:131080418:CTCA:C	acceptor_loss	1.0000
3:131080419:TCA:T	acceptor_loss	1.0000
3:131080420:CAG:C	acceptor_loss	1.0000
3:131080422:G:GC	acceptor_loss	1.0000
3:131080422:GA:G	acceptor_gain	1.0000
3:131080585:TGAGG:T	donor_loss	1.0000
3:131080587:AGG:A	donor_loss	1.0000
3:131080589:G:GC	donor_loss	1.0000
3:131080590:T:G	donor_loss	1.0000
3:131097599:A:AG	acceptor_gain	1.0000
3:131097600:A:G	acceptor_gain	1.0000
3:131109797:TTTCA:T	acceptor_loss	1.0000
3:131109798:TTCAG:T	acceptor_loss	1.0000
3:131109799:TCAG:T	acceptor_loss	1.0000
3:131109801:A:AG	acceptor_gain	1.0000
3:131109801:AG:A	acceptor_gain	1.0000
3:131109801:AGGGC:A	acceptor_loss	1.0000
3:131109802:G:GG	acceptor_gain	1.0000
3:131109802:GG:G	acceptor_gain	1.0000
3:131109917:GAGAG:G	donor_gain	1.0000
3:131109919:GAG:G	donor_gain	1.0000
3:131109922:G:GC	donor_loss	1.0000
3:131109922:G:GG	donor_gain	1.0000
3:131109923:T:G	donor_loss	1.0000
3:131162406:A:AG	acceptor_gain	1.0000
3:131162407:G:GG	acceptor_gain	1.0000
3:131162519:G:GT	donor_gain	1.0000
3:131162525:G:GT	donor_gain	1.0000
3:131162525:GAA:G	donor_gain	1.0000

AlphaMissense

4279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:131132762:A:C	D158A	0.997
3:131080435:G:C	K61N	0.996
3:131080435:G:T	K61N	0.996
3:131132759:G:C	R157P	0.996
3:131133955:T:A	W216R	0.996
3:131133955:T:C	W216R	0.996
3:131132762:A:T	D158V	0.995
3:131132763:C:A	D158E	0.995
3:131132763:C:G	D158E	0.995
3:131133907:A:C	S200R	0.995
3:131133909:T:A	S200R	0.995
3:131133909:T:G	S200R	0.995
3:131152657:G:C	R275T	0.995
3:131152658:A:C	R275S	0.995
3:131152658:A:T	R275S	0.995
3:131132762:A:G	D158G	0.994
3:131132765:T:C	L159S	0.994
3:131133834:T:A	D175E	0.994
3:131133834:T:G	D175E	0.994
3:131152434:T:C	F232L	0.994
3:131152436:C:A	F232L	0.994
3:131152436:C:G	F232L	0.994
3:131132769:G:C	K160N	0.993
3:131132769:G:T	K160N	0.993
3:131080527:T:A	V92D	0.991
3:131132755:C:G	H156D	0.991
3:131132767:A:G	K160E	0.991
3:131133833:A:C	D175A	0.991
3:131133950:A:C	D214A	0.991
3:131133949:G:C	D214H	0.990

dbSNP variants (sampled 300 via entrez): RS1000005720 (3:131082637 G>A), RS1000007974 (3:131104753 G>A,C), RS1000035083 (3:131222126 T>C), RS1000044908 (3:131044548 G>A), RS1000051169 (3:131267138 A>C,G), RS1000052879 (3:131101565 T>C), RS1000061374 (3:131189462 T>A,C), RS1000065168 (3:131093412 G>A), RS1000065319 (3:131232594 A>G), RS1000073002 (3:131188960 A>G), RS1000085072 (3:131101199 C>T), RS1000087686 (3:131052391 C>G), RS1000095905 (3:131326684 G>A), RS1000105562 (3:131144495 G>A,T), RS1000119539 (3:131200424 C>G,T)

Disease associations

OMIM: gene MIM:609779 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002589_3	Hippocampal sclerosis	8.000000e-06
GCST003114_12	Carotid intima media thickness	6.000000e-06
GCST008152_181	Weight	8.000000e-06
GCST008755_11	Phenylephrine infusion rate during anesthesia	9.000000e-06
GCST010922_2	Hip bone mineral density and total body fat mass (bivariate analysis)	1.000000e-09
GCST012194_2	Obsessive-compulsive traits	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524130 (PROTEIN FAMILY), CHEMBL5638 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 32,930 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL5416410	DASATINIB	4	655
CHEMBL475251	R-406	2	762

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	5.81	pKi

ChEMBL bioactivities

18 potent at pChembl≥5 of 18 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	170	nM	R-406
6.72	Kd	190	nM	VEMURAFENIB
6.72	Kd	190	nM	PLX-4720
6.54	IC50	290	nM	STAUROSPORINE
6.33	Kd	470	nM	DASATINIB
6.19	Kd	650	nM	BOSUTINIB
6.12	IC50	752	nM	STAUROSPORINE
6.12	IC50	768	nM	STAUROSPORINE
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	CHEMBL1908396
5.92	Kd	1200	nM	FEDRATINIB
5.52	Kd	3000	nM	CHEMBL386051
5.51	Kd	3100	nM	STAUROSPORINE

PubChem BioAssay actives

15 with measured affinity, of 559 total; 9 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	1948830: Inhibition of NEK11 (unknown origin) assessed as dissociation constant	kd	0.1700	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	624725: Binding constant for NEK11 kinase domain	kd	0.1900	uM
Vemurafenib	1948830: Inhibition of NEK11 (unknown origin) assessed as dissociation constant	kd	0.1900	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	1715246: Inhibition of human NEK11 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.2900	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	624725: Binding constant for NEK11 kinase domain	kd	0.4700	uM
Bosutinib	624725: Binding constant for NEK11 kinase domain	kd	0.6500	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	624725: Binding constant for NEK11 kinase domain	kd	1.1000	uM
Fedratinib	1948830: Inhibition of NEK11 (unknown origin) assessed as dissociation constant	kd	1.2000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	1948830: Inhibition of NEK11 (unknown origin) assessed as dissociation constant	kd	3.0000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
butyraldehyde	decreases expression	1
tobacco tar	increases expression	1
potassium chromate(VI)	increases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

141 unique, capped per target: 141 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

Clinical trials (associated diseases)

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