NEK1

Summary

NEK1 (NIMA related kinase 1, HGNC:7744) is a protein-coding gene on chromosome 4q33, encoding Serine/threonine-protein kinase Nek1 (Q96PY6). Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity.

The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4750 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis, susceptibility to, 24 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 1,051 total — 50 pathogenic, 46 likely-pathogenic
• Phenotypes (HPO): 161
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001199397

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7744
Approved symbol	NEK1
Name	NIMA related kinase 1
Location	4q33
Locus type	gene with protein product
Status	Approved
Aliases	NY-REN-55, KIAA1901
Ensembl gene	ENSG00000137601
Ensembl biotype	protein_coding
OMIM	604588
Entrez	4750

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 13 protein_coding, 7 retained_intron, 7 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000439128, ENST00000505119, ENST00000507142, ENST00000509912, ENST00000510108, ENST00000510533, ENST00000511633, ENST00000512193, ENST00000638824, ENST00000685111, ENST00000685677, ENST00000686697, ENST00000687054, ENST00000687219, ENST00000687528, ENST00000687643, ENST00000688487, ENST00000688653, ENST00000688934, ENST00000689190, ENST00000690540, ENST00000690631, ENST00000690685, ENST00000692218, ENST00000692450, ENST00000692868, ENST00000693085, ENST00000693604, ENST00000859053, ENST00000859054, ENST00000937788

RefSeq mRNA: 11 — MANE Select: NM_001199397 NM_001199397, NM_001199398, NM_001199399, NM_001199400, NM_001374418, NM_001374419, NM_001374420, NM_001374421, NM_001374422, NM_001374423, NM_012224

CCDS: CCDS47162, CCDS56348, CCDS56349, CCDS56350, CCDS56351, CCDS93668

Canonical transcript exons

ENST00000507142 — 36 exons

Exon	Start	End
ENSE00001016027	169555720	169555851
ENSE00001208562	169424553	169424800
ENSE00001224645	169401652	169401860
ENSE00001224678	169433545	169433665
ENSE00001224691	169463243	169463395
ENSE00001224711	169477432	169477497
ENSE00001224729	169507037	169507132
ENSE00001224737	169507715	169507792
ENSE00001224745	169508248	169508331
ENSE00001224753	169537809	169537911
ENSE00001224796	169400225	169400357
ENSE00001308282	169602008	169602104
ENSE00001352776	169400521	169400651
ENSE00001352780	169406596	169406747
ENSE00001352785	169426146	169426234
ENSE00001352792	169438083	169438259
ENSE00001352799	169477124	169477352
ENSE00001352809	169479403	169479534
ENSE00001352974	169602514	169602678
ENSE00001417504	169612020	169612143
ENSE00001479678	169508769	169508852
ENSE00002047849	169612222	169612583
ENSE00002048343	169392809	169394523
ENSE00003470719	169561832	169561891
ENSE00003492614	169576928	169577079
ENSE00003518458	169589447	169589514
ENSE00003552376	169561480	169561554
ENSE00003575091	169561687	169561737
ENSE00003590281	169588649	169588735
ENSE00003590402	169580842	169580902
ENSE00003607787	169555932	169556095
ENSE00003619741	169590726	169590809
ENSE00003650802	169562137	169562196
ENSE00003667433	169585349	169585549
ENSE00003670473	169599100	169599197
ENSE00003683751	169587559	169587613

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3384 / max 143.5361, expressed in 1728 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54809	9.0135	1727
54807	0.2633	45
54808	0.0616	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.88	gold quality
trigeminal ganglion	UBERON:0001675	98.18	gold quality
oocyte	CL:0000023	96.47	gold quality
dorsal root ganglion	UBERON:0000044	96.40	gold quality
cranial nerve II	UBERON:0000941	96.27	gold quality
sural nerve	UBERON:0015488	94.38	gold quality
medial globus pallidus	UBERON:0002477	93.83	gold quality
sperm	CL:0000019	93.49	gold quality
globus pallidus	UBERON:0001875	93.25	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.95	gold quality
tibial nerve	UBERON:0001323	92.86	gold quality
substantia nigra pars compacta	UBERON:0001965	92.39	gold quality
mammary duct	UBERON:0001765	91.94	gold quality
male germ cell	CL:0000015	91.83	gold quality
caput epididymis	UBERON:0004358	91.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.45	gold quality
lateral globus pallidus	UBERON:0002476	91.40	gold quality
epithelium of mammary gland	UBERON:0003244	91.37	gold quality
endothelial cell	CL:0000115	91.09	silver quality
bronchial epithelial cell	CL:0002328	90.73	gold quality
inferior vagus X ganglion	UBERON:0005363	90.73	gold quality
olfactory bulb	UBERON:0002264	90.70	gold quality
medulla oblongata	UBERON:0001896	90.62	gold quality
ventral tegmental area	UBERON:0002691	90.62	gold quality
superior vestibular nucleus	UBERON:0007227	90.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.88	gold quality
tendon	UBERON:0000043	89.83	gold quality
entorhinal cortex	UBERON:0002728	89.42	gold quality
calcaneal tendon	UBERON:0003701	89.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.11
E-HCAD-31	no	1.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YBX3

miRNA regulators (miRDB)

107 targeting NEK1, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302C-5P	99.97	72.56	3642
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-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mapping studies of NEK1 regulatory domain indicate interaction with most of the proteins known to take part in etiology of polycystic kidney disease, in double-strand DNA break repair at the G2/M cell-cycle transition phase, or in neural cell development. (PMID:14690447)
• Nek1 may function as a kinase early in the DNA damage response pathway. (PMID:15604234)
• These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair. (PMID:18843199)
• Data report that NEK1 and CLASP2 colocalize with FEZ1 in a perinuclear region in mammalian cells, and observed that coiled-coil interactions occur between FEZ1/CLASP2 and FEZ1/NEK1 in vitro. (PMID:19924516)
• these data provide a mechanism to explain how Nek1 regulates cell death by affecting the opening and closing of VDAC1. (PMID:20230784)
• Nek1 is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage. (PMID:20501547)
• absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology in vivo. (PMID:21211617)
• results demonstrate that Nek1 is important for proper checkpoint control and characterize for the first time a DNA damage response that does not directly involve one of the known upstream mediator kinases, ATM or ATR (PMID:21301226)
• The present case provides evidence for a correlation of NEK1 mutation with short rib-polydactyly syndrome type II (Majewski. (PMID:22482978)
• This study confirms that NEK1 is one gene causing SRP type II but also reports mutations in DYNC2H1, expanding the phenotypic spectrum of DYNC2H1 mutations. (PMID:22499340)
• Nek1 may suppress cilia by phosphorylating pVHL, which is critical to microtubule stabilization and ciliary stability. (PMID:23255108)
• as an ATR-associated kinase, Nek1 enhances the stability and activity of ATR-ATRIP before DNA damage, priming ATR-ATRIP for a robust DNA damage response (PMID:23345434)
• Nek1 may facilitate S-phase progression by interacting with Ku80 and regulating chromatin loading of replication factors. (PMID:23851348)
• C21ORF2 functions in the same pathway as NEK1 in DNA damage repair. (PMID:26290490)
• This study shown that the NEK1 is a novel in patient with familial amyotrophic lateral sclerosis. (PMID:26945885)
• Nek1 overexpression in gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). (PMID:27251576)
• Nek1 phosphorylates Rad54 and regulates Rad51 removal to orchestrate homologous recombination and replication fork stability. (PMID:27264870)
• Mutation in NEK1 gene is associated with amyotrophic lateral sclerosis. (PMID:27455347)
• Compound heterozygous variants in NEK1 were identified in two brothers with Mohr syndrome. The nonsense variant c.1226G>A, p.(Trp409*), results in nonsense-associated alternative splicing. Ciliation in patient fibroblasts is drastically reduced. (PMID:27530628)
• The skeletal phenotype of our patient was milder than those of previously reported cases with NEK1 mutations and those with axial SMD harboring C21orf2 mutations. Phenotypes associated with NEK1 mutations are variable and the phenotype-genotype corelation in skeletal ciliopathies is challenging (PMID:28123176)
• Following DNA damage, addition of the TLK1 inhibitor, THD, or overexpression of NEK1-T141A mutant impaired ATR and Chk1 activation, indicating the existence of a TLK1>NEK1>ATR>Chk1 pathway. Indeed, overexpression of the NEK1-T141A mutant resulted in an altered cell cycle response after exposure of cells to oxidative stress, including bypass of G1 arrest and implementation of an intra S-phase checkpoint. (PMID:28426283)
• NEK1 kinase domain structure and its dynamic protein interactome after exposure to cisplatin have been reported. (PMID:28710492)
• NEK1 variants may modify disease presentation of driving mutations. (PMID:28935222)
• We provide novel evidence for association of NEK1 with ALS in Chinese, reporting variants in these genes not previously found in Europeans. (PMID:29149916)
• evidence that a NEK1 mutation associated with amyotrophic lateral sclerosis leads to NEK1 haploinsufficiency in human MNs and to increased DNA damage leading to increased vulnerability and motoneuronal death. (PMID:29929116)
• Study established a NEK1 mutant frequency of 0.8% in Chinese Amyotrophic lateral sclerosis (ALS) patients, further expanded its spectrum of variants, and highlighted the possibility of coexistence with variants in additional ALS genes in NEK1 loss-of-function carriers. (PMID:30093141)
• These findings showed that VHL regulates NEK1 via both HIF-2alpha pathway and ubiquitin-proteasome pathway in renal cancer cells. (PMID:30635121)
• Targeting the TLK1/NEK1 axis might be a novel therapy for PCa. (PMID:30737777)
• Authors believe that this TLK1-Nek1 mediated DDR axis is likely to be a common adaptive response during the transition of PCa cells toward androgen-insensitive growth, and hence CRPC progression. (PMID:30928383)
• 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)
• The TLK1/Nek1 axis contributes to mitochondrial integrity and apoptosis prevention via phosphorylation of VDAC1. (PMID:31914854)
• Fractionation-Dependent Radiosensitization by Molecular Targeting of Nek1. (PMID:32429458)
• Hand-onset weakness is a common feature of ALS patients with a NEK1 loss-of-function variant. (PMID:32462798)
• Loss-of-function variants in NEK1 are associated with an increased risk of sporadic ALS in the Japanese population. (PMID:32920598)
• Novel variants and cellular studies on patients’ primary fibroblasts support a role for NEK1 missense variants in ALS pathogenesis. (PMID:33445179)
• NEK1 mutations and the risk of amyotrophic lateral sclerosis (ALS): a meta-analysis. (PMID:33462636)
• NEK1 deficiency affects mitochondrial functions and the transcriptome of key DNA repair pathways. (PMID:33740813)
• NEK1 and STMN2 short tandem repeat lengths are not associated with Australian amyotrophic lateral sclerosis risk. (PMID:35613520)
• A case of siblings with juvenile retinitis pigmentosa associated with NEK1 gene variants. (PMID:36341712)
• Genetic and clinical characteristics of ALS patients with NEK1 gene variants. (PMID:36443167)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nek1	ENSDARG00000022350
mus_musculus	Nek1	ENSMUSG00000031644
rattus_norvegicus	Nek1	ENSRNOG00000010418
drosophila_melanogaster	lic	FBGN0261524
caenorhabditis_elegans		WBGENE00004758
caenorhabditis_elegans		WBGENE00018034
caenorhabditis_elegans		WBGENE00018035

Paralogs (8): MAP2K4 (ENSG00000065559), MAP2K7 (ENSG00000076984), MAP3K4 (ENSG00000085511), MAP2K2 (ENSG00000126934), MAP2K5 (ENSG00000137764), MAP2K1 (ENSG00000169032), MAP3K2 (ENSG00000169967), MAP3K3 (ENSG00000198909)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek1 — Q96PY6 (reviewed: Q96PY6)

Alternative names: Never in mitosis A-related kinase 1, Renal carcinoma antigen NY-REN-55

All UniProt accessions (11): A0A8I5KQ77, A0A8I5KRM5, A0A8I5KSI3, A0A8I5KT19, A0A8I5KUL6, Q96PY6, A0A8I5KWD5, A0A8I5QJM8, A0A8I5QL42, D6RBG5, H0Y8M6

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Involved in DNA damage checkpoint control and for proper DNA damage repair. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death. May be implicated in the control of meiosis. Involved in cilium assembly.

Subunit / interactions. Binds to CBY2. Found in a complex with CFAP410, NEK1 and SPATA7. Interacts with CFAP410. Interacts (via Ser-1052 phosphorylated form) with 14-3-3 proteins.

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

Tissue specificity. High fetal expression in the brain and kidney.

Disease relevance. Short-rib thoracic dysplasia 6 with or without polydactyly (SRTD6) [MIM:263520] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly). Amyotrophic lateral sclerosis 24 (ALS24) [MIM:617892] A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Disease susceptibility is associated with variants affecting the gene represented in this entry. Orofaciodigital syndrome 2 (OFD2) [MIM:252100] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD2 is an autosomal recessive form characterized by cleft lip/palate, lobulated tongue with nodules, dental anomalies, maxillary hypoplasia, conductive hearing loss, polydactyly, syndactyly, brachydactyly, and mesomelic lower limb shortening. The disease may be caused by variants affecting the gene represented in this entry.

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

Isoforms (6)

UniProt ID	Names	Canonical?
Q96PY6-1	1	yes
Q96PY6-2	2
Q96PY6-3	3
Q96PY6-4	4
Q96PY6-5	5
Q96PY6-6	6

RefSeq proteins (11): NP_001186326, NP_001186327, NP_001186328, NP_001186329, NP_001361347, NP_001361348, NP_001361349, NP_001361350, NP_001361351, NP_001361352, NP_036356 (=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
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 (81 total): sequence variant 20, modified residue 15, helix 14, strand 8, splice variant 6, region of interest 5, sequence conflict 3, compositionally biased region 3, binding site 2, turn 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4B9D	X-RAY DIFFRACTION	1.9
4APC	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PY6-F1	57.81	0.18

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): 128 (proton acceptor)

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

Post-translational modifications (15): 156, 162, 414, 418, 428, 438, 653, 661, 664, 798, 834, 868, 881, 1052, 1126

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9861718	Regulation of pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-70268	Pyruvate metabolism

MSigDB gene sets: 491 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, ATF_B, SA_G2_AND_M_PHASES, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GEORGES_CELL_CYCLE_MIR192_TARGETS, AAAYRNCTG_UNKNOWN, GOCC_MICROTUBULE_ORGANIZING_CENTER, BROWNE_HCMV_INFECTION_48HR_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CILIUM_ORGANIZATION, BROWNE_HCMV_INFECTION_14HR_DN, GOCC_CENTROSOME, E4F1_Q6, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (4): protein phosphorylation (GO:0006468), cell division (GO:0051301), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

GO Molecular Function (11): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), kinase activity (GO:0016301), metal ion binding (GO:0046872), 14-3-3 protein binding (GO:0071889), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): pericentriolar material (GO:0000242), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cilium (GO:0005929), centriolar satellite (GO:0034451), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Pyruvate metabolism	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein kinase activity	3
centrosome	2
phosphorylation	1
protein modification process	1
cellular process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK1	DYNC2H1	Q8NCM8	969
NEK1	ALS2	Q96Q42	746
NEK1	CHCHD10	Q8WYQ3	733
NEK1	KIF3A	Q9Y496	733
NEK1	VAPB	O95292	715
NEK1	RCC1L	Q96I51	659
NEK1	MATR3	P43243	656
NEK1	C9orf72	Q96LT7	625
NEK1	SETX	Q7Z333	612
NEK1	DYNC2I1	Q8WVS4	609
NEK1	IFT80	Q9P2H3	601
NEK1	CCNF	P41002	600
NEK1	UBQLN2	Q9UHD9	599
NEK1	A0A087WTZ4	A0A087WTZ4	596
NEK1	TARDBP	Q13148	593

IntAct

100 interactions, top by confidence:

A	B	Type	Score
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
YWHAH	NEK1	psi-mi:“MI:0915”(physical association)	0.790
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
NEK1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.620
LRRK2	NEK1	psi-mi:“MI:0407”(direct interaction)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CPNE2	HIP1	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
KIF2B	BACH1	psi-mi:“MI:0914”(association)	0.530
ODAD4	GNPAT	psi-mi:“MI:0914”(association)	0.530
TEKT4	CLOCK	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
NEK1	CFAP410	psi-mi:“MI:0914”(association)	0.510
FEZ2	NEK1	psi-mi:“MI:0915”(physical association)	0.510
FEZ1	NEK1	psi-mi:“MI:0915”(physical association)	0.510
NEK1	FEZ2	psi-mi:“MI:0915”(physical association)	0.510
ALS2	NEK1	psi-mi:“MI:0915”(physical association)	0.500
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PTPRD	NEK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (220): NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Synthetic Lethality), NEK1 (Proximity Label-MS), NEK1 (Proximity Label-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), NEK1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1L8H8C0, A0A1L8HFX9, A0A2R6X6S3, A0JM08, A2ARZ3, A2RUV4, A5WUN7, A6QP06, D4AEC2, E9Q309, O76039, P51960, Q03898, Q05935, Q06190, Q08AD1, Q08D57, Q0WPH8, Q3KQW7, Q3UTQ8, Q498L0, Q5RAU1, Q5SW79, Q5T0W9, Q5T5U3, Q5VT06, Q62770, Q66J90, Q69Z38, Q6A065, Q6DFG0, Q6DFV3, Q6IRN6, Q71M21, Q80TN7, Q8AV28, Q8C1B1, Q8IVL0, Q8IZ21

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

7 interactions.

A	Effect	B	Mechanism
NEK1	down-regulates	VDAC1	phosphorylation
NEK1	“down-regulates quantity by destabilization”	VHL	phosphorylation
TLK1	“up-regulates activity”	NEK1	phosphorylation
NEK1	“down-regulates activity”	ME1	phosphorylation
NEK1	“up-regulates activity”	ATR	binding
NEK1	“up-regulates activity”	ATRIP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Activation of BAD and translocation to mitochondria	7	102.5×	3e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	90.4×	4e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	90.4×	4e-11
Activation of BH3-only proteins	7	66.8×	3e-10
RHO GTPases activate PKNs	7	42.7×	6e-09
Intrinsic Pathway for Apoptosis	7	39.4×	1e-08
FOXO-mediated transcription	5	32.3×	6e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	23.7×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	23.2×	8e-04
intracellular protein localization	10	13.2×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

1051 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	46
Uncertain significance	457
Likely benign	290
Benign	89

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323355	NM_001199397.3(NEK1):c.2089C>T (p.Gln697Ter)	Pathogenic
1332832	NM_001199397.3(NEK1):c.1957C>T (p.Arg653Ter)	Pathogenic
1338755	NM_001199397.3(NEK1):c.213del (p.Glu72fs)	Pathogenic
1380607	NM_001199397.3(NEK1):c.2991_2992insG (p.Ser998fs)	Pathogenic
1385116	NM_001199397.3(NEK1):c.2972_2973del (p.Ile991fs)	Pathogenic
1418443	NM_001199397.3(NEK1):c.1984dup (p.Glu662fs)	Pathogenic
1453965	NM_001199397.3(NEK1):c.1129C>T (p.Gln377Ter)	Pathogenic
1455845	NM_001199397.3(NEK1):c.934del (p.Ala312fs)	Pathogenic
1458767	NM_001199397.3(NEK1):c.602del (p.His201fs)	Pathogenic
1526104	NM_001199397.3(NEK1):c.3191C>G (p.Ser1064Ter)	Pathogenic
1698378	NM_001199397.3(NEK1):c.984del (p.Lys328fs)	Pathogenic
191325	NM_001199397.3(NEK1):c.1690_1691del (p.Met564fs)	Pathogenic
193892	NM_001199397.3(NEK1):c.869-1G>T	Pathogenic
2108520	NM_001199397.3(NEK1):c.1177C>T (p.Gln393Ter)	Pathogenic
2127401	NM_001199397.3(NEK1):c.3581C>A (p.Ser1194Ter)	Pathogenic
2687850	NM_001199397.3(NEK1):c.1691T>N (p.Met564Xaa)	Pathogenic
2697738	NM_001199397.3(NEK1):c.2650_2651insCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCATCCTGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAAAAAGTACAATGTA (p.Cys883_Ile884insThrCysAsnProSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerGlyAspArgAspHisProXaaXaaXaaXaaLysLysLysLysLysLysLysLysLysValGlnCys)	Pathogenic
2708080	NM_001199397.3(NEK1):c.1198del (p.Arg400fs)	Pathogenic
2716734	NM_001199397.3(NEK1):c.2282_2283dup (p.Asp762fs)	Pathogenic
2753168	NM_001199397.3(NEK1):c.2010_2011del (p.Leu670fs)	Pathogenic
2793744	NM_001199397.3(NEK1):c.1945_1951del (p.Lys648_Glu649insTer)	Pathogenic
2812876	NM_001199397.3(NEK1):c.3726del (p.Asp1243fs)	Pathogenic
2980038	NM_001199397.3(NEK1):c.1395G>A (p.Trp465Ter)	Pathogenic
3023252	NM_001199397.3(NEK1):c.1097_1098del (p.Arg366fs)	Pathogenic
3024122	NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr)	Pathogenic
30429	NM_001199397.3(NEK1):c.869-2A>G	Pathogenic
3338116	NM_001199397.3(NEK1):c.3584-10T>A	Pathogenic
3366988	NM_001199397.3(NEK1):c.1238dup (p.Ser414fs)	Pathogenic
3390022	NM_001199397.3(NEK1):c.988del (p.His330fs)	Pathogenic
3646026	NM_001199397.3(NEK1):c.2492G>A (p.Trp831Ter)	Pathogenic

SpliceAI

5435 predictions. Top by Δscore:

Variant	Effect	Δscore
4:169400219:TCTTA:T	donor_loss	1.0000
4:169400220:CTTAC:C	donor_loss	1.0000
4:169400221:TTA:T	donor_loss	1.0000
4:169400222:TA:T	donor_loss	1.0000
4:169400223:A:AC	donor_gain	1.0000
4:169400224:C:CC	donor_gain	1.0000
4:169400224:C:CG	donor_loss	1.0000
4:169400224:CCTT:C	donor_gain	1.0000
4:169400354:TAGC:T	acceptor_gain	1.0000
4:169400354:TAGCC:T	acceptor_loss	1.0000
4:169400355:AGCCT:A	acceptor_loss	1.0000
4:169400357:CCT:C	acceptor_loss	1.0000
4:169400358:C:CC	acceptor_gain	1.0000
4:169400358:CT:C	acceptor_loss	1.0000
4:169400359:T:G	acceptor_loss	1.0000
4:169400364:C:CT	acceptor_gain	1.0000
4:169400516:CTTA:C	donor_loss	1.0000
4:169400517:TTAC:T	donor_loss	1.0000
4:169400518:TACCT:T	donor_loss	1.0000
4:169400519:A:AC	donor_gain	1.0000
4:169400519:ACC:A	donor_loss	1.0000
4:169400520:C:CC	donor_gain	1.0000
4:169400520:CCTTT:C	donor_gain	1.0000
4:169400647:GTTAT:G	acceptor_gain	1.0000
4:169400648:TTAT:T	acceptor_gain	1.0000
4:169400649:TAT:T	acceptor_gain	1.0000
4:169400650:AT:A	acceptor_gain	1.0000
4:169400652:C:CC	acceptor_gain	1.0000
4:169401637:A:C	donor_gain	1.0000
4:169401648:GCAC:G	donor_loss	1.0000

AlphaMissense

8495 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:169585418:T:A	R246S	1.000
4:169585418:T:G	R246S	1.000
4:169585419:C:G	R246T	1.000
4:169585524:A:G	L211P	1.000
4:169585547:A:C	F203L	1.000
4:169585547:A:T	F203L	1.000
4:169585549:A:G	F203L	1.000
4:169587596:C:T	G190E	1.000
4:169587597:C:A	G190W	1.000
4:169587597:C:G	G190R	1.000
4:169587597:C:T	G190R	1.000
4:169587604:C:A	W187C	1.000
4:169587604:C:G	W187C	1.000
4:169587606:A:G	W187R	1.000
4:169587606:A:T	W187R	1.000
4:169588706:C:T	G165E	1.000
4:169588707:C:A	G165W	1.000
4:169588707:C:G	G165R	1.000
4:169588707:C:T	G165R	1.000
4:169589453:A:G	L153P	1.000
4:169589462:G:T	A150D	1.000
4:169589465:A:T	I149N	1.000
4:169589468:C:T	G148E	1.000
4:169589469:C:G	G148R	1.000
4:169589469:C:T	G148R	1.000
4:169589470:A:C	F147L	1.000
4:169589470:A:T	F147L	1.000
4:169589471:A:G	F147S	1.000
4:169589472:A:G	F147L	1.000
4:169589473:A:C	D146E	1.000

dbSNP variants (sampled 300 via entrez): RS1000001017 (4:169549720 G>T), RS1000014202 (4:169611474 G>A), RS1000032137 (4:169549529 T>A), RS1000044673 (4:169456542 C>G,T), RS1000066307 (4:169611736 T>C), RS1000075487 (4:169414160 C>T), RS1000080130 (4:169439212 T>C), RS1000088112 (4:169484763 A>G,T), RS1000096479 (4:169456812 T>C), RS1000114841 (4:169432570 A>G), RS10001274 (4:169550032 T>C), RS1000129974 (4:169592735 A>G), RS1000130374 (4:169480424 T>C), RS10001612 (4:169544500 T>G), RS1000180869 (4:169522877 T>C)

Disease associations

OMIM: gene MIM:604588 | disease phenotypes: MIM:263520, MIM:617892, MIM:252100, MIM:613091, MIM:269860, MIM:208500

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis, susceptibility to, 24	Definitive	Autosomal dominant
short-rib thoracic dysplasia 6 with or without polydactyly	Definitive	Autosomal recessive
orofaciodigital syndrome type II	Supportive	Autosomal recessive
short rib-polydactyly syndrome, Majewski type	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis, susceptibility to, 24	Definitive	AD

Mondo (12): short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894), amyotrophic lateral sclerosis, susceptibility to, 24 (MONDO:0054750), orofaciodigital syndrome type II (MONDO:0009642), connective tissue disorder (MONDO:0003900), short rib-polydactyly syndrome (MONDO:0015461), asphyxiating thoracic dystrophy 3 (MONDO:0013127), motor neuron disorder (MONDO:0020128), amyotrophic lateral sclerosis (MONDO:0004976), Beemer-Langer syndrome (MONDO:0010024), Jeune syndrome (MONDO:0018770), asphyxiating thoracic dystrophy 1 (MONDO:0008831), short rib-polydactyly syndrome, Majewski type (MONDO:0019662)

Orphanet (9): Orofaciodigital syndrome type 2 (Orphanet:2751), Short rib-polydactyly syndrome (Orphanet:1505), Jeune syndrome (Orphanet:474), Short rib-polydactyly syndrome, Majewski type (Orphanet:93269), Short rib-polydactyly syndrome, Saldino-Noonan type (Orphanet:93270), Short rib-polydactyly syndrome, Verma-Naumoff type (Orphanet:93271), Motor neuron disease (Orphanet:98503), Amyotrophic lateral sclerosis (Orphanet:803), Short rib-polydactyly syndrome, Beemer-Langer type (Orphanet:93268)

HPO phenotypes

161 total (30 of 161 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000050	Hypoplastic male external genitalia
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000113	Polycystic kidney dysplasia
HP:0000161	Median cleft upper lip
HP:0000171	Microglossia
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000191	Accessory oral frenulum
HP:0000199	Tongue nodules
HP:0000217	Xerostomia
HP:0000218	High palate
HP:0000220	Velopharyngeal insufficiency
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000272	Malar flattening
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000405	Conductive hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000456	Bifid nasal tip
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000556	Retinal dystrophy

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002539_54	Schizophrenia	1.000000e-09
GCST003542_34	Night sleep phenotypes	8.000000e-06
GCST004521_54	Autism spectrum disorder or schizophrenia	9.000000e-09
GCST004946_50	Schizophrenia	7.000000e-11
GCST006803_41	Schizophrenia	3.000000e-08
GCST009205_3	Supramarginal gyrus volume	8.000000e-06
GCST011494_99	Daytime nap	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D003240	Connective Tissue Diseases	C17.300
D016472	Motor Neuron Disease	C10.574.562; C10.668.467
D012779	Short Rib-Polydactyly Syndrome	C05.116.099.708.857; C05.660.585.600.750; C16.131.077.850; C16.131.621.585.600.750
C537571	Jeune syndrome (supp.)
C537599	Short rib-polydactyly syndrome, Beemer type (supp.)
C537602	Short rib-polydactyly syndrome, Verma-Naumoff type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524130 (PROTEIN FAMILY), CHEMBL5855 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 28,252 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL603469	LESTAURTINIB	3
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1908397	KW-2449	1	622
CHEMBL2140408	AMG-900	1	675
CHEMBL2180604	TAK-593	1	170
CHEMBL482967	CYC-116	1	651
CHEMBL574738	AST-487	1	451

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 31 [PMID: 20936789]	Inhibition	6.77	pIC50

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
(3R,4R)-3-methoxy-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	IC50	3.93 nM	US-10189849: CDK inhibitors
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM

ChEMBL bioactivities

298 potent at pChembl≥5 of 307 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.42	IC50	0.38	nM	CHEMBL3667204
9.37	IC50	0.43	nM	CHEMBL3667261
9.30	IC50	0.5	nM	CHEMBL3667249
9.27	IC50	0.54	nM	CHEMBL3667248
9.24	IC50	0.57	nM	CHEMBL3667234
9.20	IC50	0.63	nM	CHEMBL3667204
9.19	IC50	0.64	nM	CHEMBL3672289
9.17	IC50	0.67	nM	CHEMBL3667250
9.14	IC50	0.73	nM	CHEMBL3667224
9.13	IC50	0.74	nM	CHEMBL3667246
9.13	IC50	0.74	nM	CHEMBL3672360
9.12	Kd	0.753	nM	CHEMBL5653589
9.11	IC50	0.78	nM	CHEMBL3667207
9.11	IC50	0.78	nM	CHEMBL3667241
9.09	IC50	0.81	nM	CHEMBL3667233
9.09	IC50	0.82	nM	CHEMBL3672235
9.06	IC50	0.88	nM	CHEMBL3667245
9.06	IC50	0.88	nM	CHEMBL3672269
9.05	IC50	0.9	nM	CHEMBL3667219
9.04	IC50	0.92	nM	CHEMBL3672246
9.04	ED50	0.912	nM	CHEMBL5653589
9.01	IC50	0.97	nM	CHEMBL3667251
9.00	IC50	1	nM	CHEMBL3672339
8.96	IC50	1.1	nM	CHEMBL3667217
8.96	IC50	1.1	nM	CHEMBL3672259
8.92	IC50	1.2	nM	CHEMBL3667217
8.92	IC50	1.2	nM	CHEMBL3672240
8.89	IC50	1.3	nM	CHEMBL3672253
8.89	IC50	1.3	nM	CHEMBL3672263
8.89	IC50	1.3	nM	CHEMBL3672266
8.89	IC50	1.3	nM	CHEMBL3672276
8.89	IC50	1.3	nM	CHEMBL3672283
8.89	IC50	1.3	nM	CHEMBL3672292
8.89	IC50	1.3	nM	CHEMBL3672301
8.85	IC50	1.4	nM	CHEMBL3672274
8.85	IC50	1.4	nM	CHEMBL3672329
8.82	IC50	1.5	nM	CHEMBL3672297
8.80	IC50	1.6	nM	CHEMBL3667221
8.77	IC50	1.7	nM	CHEMBL5933800
8.74	IC50	1.8	nM	CHEMBL3667203
8.74	IC50	1.8	nM	CHEMBL3672310
8.72	IC50	1.9	nM	CHEMBL3667221
8.72	IC50	1.9	nM	CHEMBL3667263
8.72	IC50	1.9	nM	CHEMBL3672238
8.72	IC50	1.9	nM	CHEMBL3672242
8.72	IC50	1.9	nM	CHEMBL3672243
8.70	IC50	2	nM	CHEMBL3667242
8.70	IC50	2	nM	CHEMBL3667259
8.70	IC50	2	nM	CHEMBL3667222
8.70	IC50	2	nM	CHEMBL3672244

PubChem BioAssay actives

61 with measured affinity, of 812 total; 46 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148860: Binding affinity to human NEK1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0008	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	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.0091	uM
methyl 3-(3-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzoate	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.0115	uM
methyl 3-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzoate	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.0625	uM
Momelotinib	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	0.1000	uM
methyl 3-(3-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzoate	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.1230	uM
3-(3-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzonitrile	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.1290	uM
methyl 3-(3-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzoate	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.1400	uM
methyl 3-[3-(3-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]benzoate	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.1660	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	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	0.1700	uM
(2R,3R,4R)-1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-2,3-dimethylpiperidine-4-carboxylic acid	537146: Inhibition of NEK1 after 1 hr at room temperature by caliper method	ic50	0.1700	uM
N-[(2R)-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901496: Inhibition of human recombinant NEK1 (1 to 505 residues) using RLGRDKYKTLRQIRQ as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric scintillation counting assay	ic50	0.3300	uM
N-[5-[2-(cyclopropanecarbonylamino)imidazo[1,2-b]pyridazin-6-yl]oxy-2-methylphenyl]-2,5-dimethylpyrazole-3-carboxamide	1425085: 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	0.3650	uM
Dabrafenib	1425085: 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	0.4770	uM
(3E,5E)-3,5-bis(pyridin-2-ylmethylidene)piperidin-4-one	734763: Inhibition of recombinant NEK1 (unknown origin) by FRET-based Z’-LYTE assay	ic50	0.5000	uM
6-(2,4-difluorophenyl)sulfonyl-2-(1H-indol-5-ylamino)-8-methylpyrido[2,3-d]pyrimidin-7-one	1269890: Inhibition of human NEK1 using MBP as substrate	ic50	0.6300	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-N-phenylpyrimidine-2,4-diamine	1830876: Inhibition of human NEK1 using myelin basic protein as substrate assessed as residual activity in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay relative to control	ic50	0.8500	uM
N-[(2S)-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	0.9900	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425085: 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	1.0990	uM
N-[(2R)-1-hydroxy-3-phenylpropan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	1.3000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148860: Binding affinity to human NEK1 incubated for 45 mins by Kinobead based pull down assay	kd	1.5451	uM
N-[(2R)-1-hydroxy-3-(4-hydroxyphenyl)propan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	1.6000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625068: Binding constant for NEK1 kinase domain	kd	1.8000	uM
N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	1.9000	uM
N-[(2S)-1-hydroxy-3-(4-hydroxyphenyl)propan-2-yl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	2.0000	uM
N-(2-hydroxyethyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901496: Inhibition of human recombinant NEK1 (1 to 505 residues) using RLGRDKYKTLRQIRQ as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric scintillation counting assay	ic50	2.0000	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425085: 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	2.3810	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	507643: Binding affinity to NEK1	kd	2.5000	uM
1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]piperidine-4-carboxylic acid	537146: Inhibition of NEK1 after 1 hr at room temperature by caliper method	ic50	2.6000	uM
N-(2-hydroxyethyl)-N-methyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	2.7000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	3.1000	uM
Fedratinib	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	3.4000	uM
(3E,5E)-1-methyl-3,5-bis(pyridin-2-ylmethylidene)piperidin-4-one	734763: Inhibition of recombinant NEK1 (unknown origin) by FRET-based Z’-LYTE assay	ic50	3.5000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625068: Binding constant for NEK1 kinase domain	kd	3.8000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	435533: Binding constant for NEK1 kinase domain	kd	3.9000	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769504: Binding affinity to NEK1 (unknown origin)	kd	4.0000	uM
N-[2-(dimethylamino)ethyl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901496: Inhibition of human recombinant NEK1 (1 to 505 residues) using RLGRDKYKTLRQIRQ as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric scintillation counting assay	ic50	4.3000	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573315: Binding affinity to NEK1 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	5.0430	uM
2,5-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573315: Binding affinity to NEK1 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	5.1460	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	5.2000	uM
N-(2-hydroxy-2-methylpropyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	5.8000	uM
N-(2-piperidin-1-ylethyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	6.6000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	1948822: Inhibition of NEK1 (unknown origin) assessed as dissociation constant	kd	8.3000	uM
2-[[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]sulfonylamino]ethyl acetate	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	8.8000	uM
6-[3-[(5-chloro-2-methoxy-3-pyridinyl)sulfonylamino]-2,6-difluorophenyl]-N-methylimidazo[1,5-a]pyrazine-1-carboxamide	2103374: Inhibition of NEK1 in human MOLM16 cells	ic50	9.3000	uM
N-[2-(diethylamino)ethyl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	1901498: Inhibition of human recombinant NEK1 (1 to 505 residues) using ULight-p70 S6K peptide as substrate incubated for 30 mins by LANCE Ultra TR-FRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	increases phosphorylation	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	decreases expression	1
Hydrogen Peroxide	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

288 unique, capped per target: 288 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_A8DV	HeLa NEK1 KO	Cancer cell line	Female
CVCL_TA30	HAP1 NEK1 (-) 1	Cancer cell line	Male
CVCL_TA31	HAP1 NEK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT01951924	PHASE3	COMPLETED	LIME Study (LFB IVIg MMN Efficacy Study)
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT00076687	PHASE2	COMPLETED	Safety Study of Botulinum Toxin Type A in Post-Upper Limb Stroke Patients With Reduced Lung Function
NCT00324454	PHASE2	COMPLETED	Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease
NCT02469896	PHASE2	COMPLETED	A Trial of Tocilizumab in ALS Subjects
NCT03114215	PHASE2	COMPLETED	Effect of MD1003 in Amyotrophic Lateral Sclerosis
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03196375	PHASE2	TERMINATED	A Study to Assess FLX-787 in Subjects With Motor Neuron Disease Experiencing Muscle Cramps.
NCT03508453	PHASE2	WITHDRAWN	IC14 for Treatment of Amyotrophic Lateral Sclerosis
NCT03705390	PHASE2	TERMINATED	A Safety and Tolerability Study of ILB® in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT04579666	PHASE2	TERMINATED	MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS)
NCT04788745	PHASE2	COMPLETED	Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)
NCT06315608	PHASE2	NOT_YET_RECRUITING	MRG-001 in Patients With Amyotrophic Lateral Sclerosis
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)