NEK10

Summary

NEK10 (NIMA related kinase 10, HGNC:18592) is a protein-coding gene on chromosome 3p24.1, encoding Serine/threonine-protein kinase Nek10 (Q6ZWH5). Plays a role in the cellular response to UV irradiation.

Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44.

Source: NCBI Gene 152110 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 44 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 22
• Clinical variants (ClinVar): 111 total — 5 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001394966

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18592
Approved symbol	NEK10
Name	NIMA related kinase 10
Location	3p24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32685
Ensembl gene	ENSG00000163491
Ensembl biotype	protein_coding
OMIM	618726
Entrez	152110

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000295720, ENST00000341435, ENST00000383771, ENST00000424275, ENST00000429845, ENST00000435584, ENST00000435750, ENST00000460447, ENST00000474938, ENST00000491627, ENST00000498182, ENST00000574215, ENST00000691995, ENST00000898306, ENST00000936071, ENST00000945408

RefSeq mRNA: 13 — MANE Select: NM_001394966 NM_001031741, NM_001304384, NM_001394963, NM_001394964, NM_001394965, NM_001394966, NM_001394967, NM_001394968, NM_001394969, NM_001394970, NM_001394971, NM_152534, NM_199347

CCDS: CCDS46781, CCDS77713, CCDS93229

Canonical transcript exons

ENST00000691995 — 36 exons

Exon	Start	End
ENSE00001075264	27115940	27115995
ENSE00001075267	27116075	27116127
ENSE00001075271	27131880	27131990
ENSE00001075282	27119760	27119868
ENSE00001594377	27295613	27295690
ENSE00001634859	27291484	27291586
ENSE00001668238	27304747	27304971
ENSE00001671587	27293588	27293652
ENSE00001728256	27310949	27311016
ENSE00001736215	27290617	27290754
ENSE00001753472	27297179	27297240
ENSE00001764383	27308926	27309005
ENSE00001765941	27307859	27307945
ENSE00001792675	27312099	27312177
ENSE00001804692	27301696	27301835
ENSE00003467917	27344272	27344370
ENSE00003485691	27192029	27192242
ENSE00003485779	27162701	27162738
ENSE00003495276	27174439	27174525
ENSE00003503595	27287698	27287743
ENSE00003510091	27284602	27284704
ENSE00003510330	27346086	27346216
ENSE00003524783	27284840	27284961
ENSE00003525379	27322177	27322261
ENSE00003530953	27352465	27352525
ENSE00003549574	27352812	27352919
ENSE00003580186	27171819	27171873
ENSE00003592109	27174650	27174833
ENSE00003597134	27141482	27141582
ENSE00003607794	27314297	27314338
ENSE00003620989	27201510	27201580
ENSE00003622446	27291262	27291390
ENSE00003624431	27202428	27202557
ENSE00003654284	27256296	27256371
ENSE00003923728	27369225	27369383
ENSE00003923920	27106484	27111320

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 92.85.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6923 / max 49.9463, expressed in 190 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41515	0.5902	159
41514	0.0615	25
41513	0.0213	10
41510	0.0193	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	92.85	gold quality
right uterine tube	UBERON:0001302	89.51	gold quality
left testis	UBERON:0004533	88.34	gold quality
right testis	UBERON:0004534	88.06	gold quality
bronchial epithelial cell	CL:0002328	86.84	gold quality
sperm	CL:0000019	86.81	gold quality
testis	UBERON:0000473	85.94	gold quality
bronchus	UBERON:0002185	85.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.40	gold quality
oviduct epithelium	UBERON:0004804	77.65	gold quality
muscle of leg	UBERON:0001383	76.80	gold quality
gastrocnemius	UBERON:0001388	76.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.12	silver quality
biceps brachii	UBERON:0001507	75.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.61	gold quality
epithelium of nasopharynx	UBERON:0001951	75.22	gold quality
apex of heart	UBERON:0002098	74.02	gold quality
fallopian tube	UBERON:0003889	73.15	gold quality
nasal cavity epithelium	UBERON:0005384	73.06	silver quality
upper arm skin	UBERON:0004263	72.95	gold quality
buccal mucosa cell	CL:0002336	72.59	silver quality
skeletal muscle tissue	UBERON:0001134	72.56	gold quality
prefrontal cortex	UBERON:0000451	71.88	gold quality
right atrium auricular region	UBERON:0006631	71.30	gold quality
heart left ventricle	UBERON:0002084	70.99	gold quality
nasal cavity mucosa	UBERON:0001826	70.38	gold quality
cardiac ventricle	UBERON:0002082	70.07	gold quality
adenohypophysis	UBERON:0002196	69.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	61.51
E-ANND-3	yes	11.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NEK10, 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-651-3P	99.94	73.48	5177
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-6859-3P	97.26	64.69	428

Literature-anchored findings (GeneRIF, showing 5)

• Nek10 physically associated with Raf-1 and MEK1 in a Raf-1-dependent manner, and the formation of this complex was necessary for Nek10-mediated MEK1 activation. (PMID:20956560)
• analysis of a bronchiectasis syndrome caused by mutations that inactivate NIMA-related kinase 10 (NEK10), a protein kinase with previously unknown in vivo functions in mammals (PMID:31959991)
• Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report. (PMID:32414360)
• NEK10 tyrosine phosphorylates p53 and controls its transcriptional activity. (PMID:32561851)
• beta-catenin turnover is regulated by Nek10-mediated tyrosine phosphorylation in A549 lung adenocarcinoma cells. (PMID:38683979)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nek10	ENSDARG00000025335
mus_musculus	Nek10	ENSMUSG00000042567
rattus_norvegicus	Nek10	ENSRNOG00000005883

Paralogs (8): NEK11 (ENSG00000114670), NEK2 (ENSG00000117650), NEK6 (ENSG00000119408), NEK9 (ENSG00000119638), NEK3 (ENSG00000136098), NEK7 (ENSG00000151414), NEK8 (ENSG00000160602), NEK5 (ENSG00000197168)

Protein

Protein identifiers

Serine/threonine-protein kinase Nek10 — Q6ZWH5 (reviewed: Q6ZWH5)

Alternative names: Never in mitosis A-related kinase 10

All UniProt accessions (5): A0A8I5KTB8, C9JJN0, Q6ZWH5, H7C000, H7C3L8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the cellular response to UV irradiation. Mediates G2/M cell cycle arrest, MEK autoactivation and ERK1/2-signaling pathway activation in response to UV irradiation. In ciliated cells of airways, it is involved in the regulation of mucociliary transport.

Subunit / interactions. Interacts with RAF1 and MAP2K1; the interaction is direct with RAF1 and required for ERK1/2-signaling pathway activation in response to UV irradiation.

Tissue specificity. Expressed in the lung.

Disease relevance. Ciliary dyskinesia, primary, 44 (CILD44) [MIM:618781] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD44 inheritance is autosomal recessive. The disease is 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 (7)

UniProt ID	Names	Canonical?
Q6ZWH5-1	1	yes
Q6ZWH5-2	2
Q6ZWH5-3	3
Q6ZWH5-4	4
Q6ZWH5-5	5
Q6ZWH5-6	6
Q6ZWH5-7	7

RefSeq proteins (13): NP_001026911, NP_001291313, NP_001381892, NP_001381893, NP_001381894, NP_001381895, NP_001381896, NP_001381897, NP_001381898, NP_001381899, NP_001381900, NP_689747, NP_955379 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR042666	Nek10_STKc	Domain
IPR050660	NEK_Ser/Thr_kinase	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 (35 total): splice variant 10, sequence variant 9, sequence conflict 4, mutagenesis site 2, region of interest 2, binding site 2, chain 1, repeat 1, domain 1, coiled-coil region 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZWH5-F1	70.23	0.29

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): 655 (proton acceptor)

Ligand- & substrate-binding residues (2): 525–533; 548

Mutagenesis-validated functional residues (2):

Position	Phenotype
548	catalytically inactive. impaired mucociliary transport.
684	increased mucociliary transport.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, CEBP_Q2, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_AUTOPHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY

GO Biological Process (6): protein phosphorylation (GO:0006468), positive regulation of protein autophosphorylation (GO:0031954), positive regulation of MAP kinase activity (GO:0043406), regulation of ERK1 and ERK2 cascade (GO:0070372), mucociliary clearance (GO:0120197), regulation of cell cycle G2/M phase transition (GO:1902749)

GO Molecular Function (8): protein kinase activity (GO:0004672), 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), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): extracellular region (GO:0005576), protein kinase complex (GO:1902911)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
phosphorylation	1
protein modification process	1
positive regulation of protein phosphorylation	1
regulation of protein autophosphorylation	1
positive regulation of protein kinase activity	1
protein autophosphorylation	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
respiratory system process	1
epithelial cilium movement involved in extracellular fluid movement	1
cell cycle G2/M phase transition	1
regulation of cell cycle phase transition	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
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cellular anatomical structure	1
transferase complex, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEK10	COX11	Q9Y6N1	779
NEK10	SLC4A7	Q9Y6M7	777
NEK10	TOX3	O15405	763
NEK10	LSP1	P33241	739
NEK10	RAD51B	O15315	586
NEK10	FCGR1BP	Q92637	541
NEK10	CFAP276	Q5T5A4	471
NEK10	MRPS30	Q9NP92	447
NEK10	MAP3K1	Q13233	446
NEK10	SMC3	Q9UQE7	440
NEK10	VWA8	A3KMH1	433
NEK10	SUMO1	P55856	430
NEK10	STXBP4	Q6ZWJ1	430
NEK10	PRKDC	P78527	429
NEK10	ATRX	P46100	422

IntAct

13 interactions, top by confidence:

A	B	Type	Score
NEK10	GLUD1	psi-mi:“MI:2364”(proximity)	0.480
NEK10	GLUD1	psi-mi:“MI:0403”(colocalization)	0.480
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
NEK10	CS	psi-mi:“MI:2364”(proximity)	0.420
NEK10	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
NEK10	PFDN6	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
NEK10		psi-mi:“MI:0914”(association)	0.350
NEK10	GPATCH4	psi-mi:“MI:0914”(association)	0.350
NEK10	MYO9A	psi-mi:“MI:0914”(association)	0.350
Map3k1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (17): NEK10 (Biochemical Activity), NEK10 (Two-hybrid), NEK10 (Affinity Capture-MS), NEK10 (Affinity Capture-RNA), MYO9A (Affinity Capture-MS), KIAA0586 (Affinity Capture-MS), PFDN6 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), VBP1 (Affinity Capture-MS), PFDN5 (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), PFDN2 (Affinity Capture-MS), NEK10 (Affinity Capture-MS), NEK10 (Affinity Capture-MS), NEK10 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA8, A2AFR3, A2AWP8, F1LXF1, O15034, O94844, O94967, O95267, P11274, P28028, Q01826, Q08BT5, Q14161, Q14CM0, Q15139, Q3UGM2, Q3UHE1, Q4R4I0, Q5R5M3, Q5VUG0, Q5XIS9, Q60611, Q62101, Q66H91, Q68FF6, Q6NZQ4, Q6PAJ1, Q6PB44, Q6ZW49, Q6ZWH5, Q80U28, Q8BWW9, Q8BZ03, Q8CGF6, Q8TCU6, Q8VDD9, Q8VI24, Q96GD3, Q9BZ71, Q9BZL6

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

1 interactions.

A	Effect	B	Mechanism
NEK10	“up-regulates activity”	TP53	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	4
Uncertain significance	73
Likely benign	9
Benign	12

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1705354	NM_001394966.1(NEK10):c.1154dup (p.Ser386fs)	Pathogenic
4294416	NM_001394966.1(NEK10):c.1985T>A (p.Met662Lys)	Pathogenic
813279	NM_001394966.1(NEK10):c.1869dup (p.His624fs)	Pathogenic
813280	NM_001394966.1(NEK10):c.2243C>T (p.Pro748Leu)	Pathogenic
813281	NM_001394966.1(NEK10):c.2317C>T (p.Arg773Cys)	Pathogenic
3064479	NM_001394966.1(NEK10):c.2182C>T (p.Pro728Ser)	Likely pathogenic
4081549	NM_001394966.1(NEK10):c.489+1G>A	Likely pathogenic
4849299	NM_001394966.1(NEK10):c.975_976insTGAGAAT (p.Val326Ter)	Likely pathogenic
813278	NM_001394966.1(NEK10):c.1230+5G>C	Likely pathogenic

SpliceAI

7207 predictions. Top by Δscore:

Variant	Effect	Δscore
3:27115992:CAGT:C	acceptor_gain	1.0000
3:27115996:C:CC	acceptor_gain	1.0000
3:27119866:TAA:T	acceptor_gain	1.0000
3:27119869:C:CC	acceptor_gain	1.0000
3:27126848:C:CA	donor_gain	1.0000
3:27131986:GGAAG:G	acceptor_gain	1.0000
3:27131987:GAAG:G	acceptor_gain	1.0000
3:27131989:AG:A	acceptor_gain	1.0000
3:27131990:GC:G	acceptor_loss	1.0000
3:27131991:C:CC	acceptor_gain	1.0000
3:27141581:TG:T	acceptor_gain	1.0000
3:27141583:C:CC	acceptor_gain	1.0000
3:27171366:AT:A	donor_gain	1.0000
3:27171396:T:TA	donor_gain	1.0000
3:27171397:C:A	donor_gain	1.0000
3:27174437:A:AC	donor_gain	1.0000
3:27174438:C:CC	donor_gain	1.0000
3:27192027:A:AC	donor_gain	1.0000
3:27192028:C:CC	donor_gain	1.0000
3:27201577:CTAT:C	acceptor_gain	1.0000
3:27202426:A:AC	donor_gain	1.0000
3:27202427:C:CC	donor_gain	1.0000
3:27284706:T:C	acceptor_gain	1.0000
3:27284706:T:TC	acceptor_gain	1.0000
3:27290658:CG:C	donor_gain	1.0000
3:27291289:T:TA	donor_gain	1.0000
3:27299534:G:GA	donor_gain	1.0000
3:27301691:AATAC:A	donor_loss	1.0000
3:27301692:ATAC:A	donor_loss	1.0000
3:27301693:TAC:T	donor_loss	1.0000

AlphaMissense

7397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:27202511:A:G	W713R	1.000
3:27202511:A:T	W713R	1.000
3:27192217:G:T	R773S	0.999
3:27202501:C:T	G716D	0.999
3:27202509:C:A	W713C	0.999
3:27202509:C:G	W713C	0.999
3:27256367:G:C	D673E	0.999
3:27256367:G:T	D673E	0.999
3:27256368:T:A	D673V	0.999
3:27256368:T:G	D673A	0.999
3:27256369:C:G	D673H	0.999
3:27284604:A:T	V671D	0.999
3:27284652:T:G	D655A	0.999
3:27284655:C:A	R654I	0.999
3:27284655:C:G	R654T	0.999
3:27290716:T:A	K548N	0.999
3:27290716:T:G	K548N	0.999
3:27131937:C:A	K1065N	0.998
3:27131937:C:G	K1065N	0.998
3:27192237:A:G	L766P	0.998
3:27192241:A:G	C765R	0.998
3:27202461:G:C	F729L	0.998
3:27202461:G:T	F729L	0.998
3:27202463:A:G	F729L	0.998
3:27202490:A:C	Y720D	0.998
3:27202497:G:C	C717W	0.998
3:27202502:C:G	G716R	0.998
3:27256359:A:G	L676P	0.998
3:27256365:A:G	F674S	0.998
3:27256368:T:C	D673G	0.998

dbSNP variants (sampled 300 via entrez): RS1000001329 (3:27260943 G>A,C), RS1000006501 (3:27357885 A>G), RS1000009715 (3:27285138 G>C), RS1000010280 (3:27174494 G>A), RS1000012762 (3:27129265 G>C), RS1000017667 (3:27327478 T>C), RS1000036821 (3:27355528 C>A), RS1000056147 (3:27258057 A>T), RS1000060169 (3:27201727 C>T), RS1000068540 (3:27236803 A>G), RS1000088329 (3:27210140 A>G), RS1000089939 (3:27223001 A>G), RS1000095241 (3:27124567 G>C), RS1000105440 (3:27365120 G>C), RS1000112009 (3:27296848 T>C)

Disease associations

OMIM: gene MIM:618726 | disease phenotypes: MIM:618781, MIM:244400

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 44	Strong	Autosomal recessive
primary ciliary dyskinesia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 44	Definitive	AR

Mondo (2): ciliary dyskinesia, primary, 44 (MONDO:0032914), primary ciliary dyskinesia (MONDO:0016575)

Orphanet (1): Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0005301	Persistent left superior vena cava

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST003588_3	Cancer (pleiotropy)	2.000000e-09
GCST003815_58	Late-onset Alzheimer’s disease	7.000000e-06
GCST003854_30	Gut microbiota (functional units)	4.000000e-08
GCST004948_1	Breast cancer	4.000000e-23
GCST004949_1	Breast cancer	2.000000e-07
GCST006166_2	Diastolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-14
GCST006167_53	Mean arterial pressure x alcohol consumption interaction (2df test)	1.000000e-11
GCST006168_35	Pulse pressure x alcohol consumption interaction (2df test)	8.000000e-13
GCST006231_19	Mean arterial pressure	3.000000e-08
GCST006434_22	Systolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-21
GCST006434_77	Systolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-12
GCST006462_7	Uterine fibroids	9.000000e-11
GCST008985_4	Triglycerides	9.000000e-06
GCST010655_1	Arterial stiffness (carotid-femoral pulse wave velocity)	2.000000e-08
GCST010796_1390	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_1391	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_1392	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_1393	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_1394	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-10
GCST010796_1395	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1396	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010989_214	Body size at age 10	3.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:1001870	late-onset Alzheimers disease
EFO:0007874	gut microbiome measurement
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0004517	arterial stiffness measurement
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3108655 (SINGLE PROTEIN), CHEMBL4524130 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,012 (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
CHEMBL3904602	LEROCICLIB	3	1,012

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Kd	0.2	nM	LEROCICLIB
6.37	Kd	430	nM	CHEMBL449216

PubChem BioAssay actives

2 with measured affinity, of 69 total; 2 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-[[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	1609449: Binding affinity to NEK10 (unknown origin)	kd	0.0002	uM
4-aminocinnoline-3-carboxamide	1948873: Inhibition of NEK10 (unknown origin) assessed as dissociation constant	kd	0.4300	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, decreases methylation	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Aflatoxin B1	increases methylation	2
propionaldehyde	increases expression	1
abrine	increases expression	1
incobotulinumtoxinA	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases expression, increases abundance	1
Endosulfan	decreases expression	1
Gallic Acid	decreases expression	1
Malathion	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Gold Compounds	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

40 unique, capped per target: 40 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3111956	Binding	Inhibition of NEK10 (unknown origin) assessed as residual activity at 10 uM after 1 hr by qPCR analysis relative to control	Design, synthesis, and biological activity of pyridopyrimidine scaffolds as novel PI3K/mTOR dual inhibitors. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_EI39	C025	Cancer cell line	Sex unspecified
CVCL_TA32	HAP1 NEK10 (-) 1	Cancer cell line	Male
CVCL_TA33	HAP1 NEK10 (-) 2	Cancer cell line	Male
CVCL_TA34	HAP1 NEK10 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03271840	Not specified	COMPLETED	Registry for Primary Ciliary Dyskinesia
NCT03279965	Not specified	UNKNOWN	MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03320382	Not specified	UNKNOWN	Multiple Breath Washout, a Clinimetric Dataset
NCT03370029	Not specified	COMPLETED	Respiratory Muscle Strength, Exercise Capacity and Physical Activity Levels in Children Primary Ciliary Dyskinesia
NCT03494894	Not specified	COMPLETED	Bacteriological Link Between Upper and Lower Airways in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT03704896	Not specified	UNKNOWN	PRospective Observational Multicentre Study on VAriability of Lung Function in Stable PCD Patients
NCT03801395	Not specified	COMPLETED	PCD New Gene Discovery
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT03832491	Not specified	COMPLETED	Effect of Game Based Approach on Oxygenation, Functional Capacity and Quality of Life in Primary Ciliary Dyskinesia
NCT04161313	Not specified	COMPLETED	Respiratory Function, Exercise Capacity and Peripheral Muscle Strength Among Patients With CF, PCD and Healthy Children
NCT04476433	Not specified	COMPLETED	Intervention in Chronic Pediatric Patients and Their Families.
NCT04489472	Not specified	UNKNOWN	The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia.
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)