NEK10

protein-coding

NIMA related kinase 10, the group of Armadillo like helical domain containing

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001394966.1

Inheritance

AD, AR

ClinVar variants

P:13U:80B:13

Top phenotype

Ciliary dyskinesia, primary, 44

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr3:27,106,484-27,369,460

External References & Databases

Ensembl (ENSG00000163491)

Transcript & Mutation Effects

hg38 • Region Span ~263.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary ciliary dyskinesiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016575

Submitter: Orphanet

ciliary dyskinesia, primary, 44STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032914

Submitter: PanelApp Australia

ciliary dyskinesia, primary, 44LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032914

Submitter: Ambry Genetics

ciliary dyskinesia, primary, 44DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032914

Submitter: ClinGen

The *NEK10* gene encodes a kinase involved in the function and growth of cilia (PMID: 29581457, PMID: 31959991). Loss-of-function variants in this gene were first identified in patients with bronchiectasis and reduced ciliary motion in cultured bronchial epithelial cells (PMID: 31959991). These features are consistent with primary ciliary dyskinesia (PCD), a condition of impaired ciliary function characterized by neonates with respiratory distress, recurrent chest infections, wet cough, and abnormalities of abdominal situs in approximately half of affected individuals. Given the ciliary function of *NEK10,* this gene has been evaluated in this curation for gene-disease association with primary ciliary dyskinesia 44. Individuals with phenotypes consistent with PCD (e.g. bronchiectasis, recurrent sinusitis, neonatal respiratory distress) who carried homozygous or compound heterozygous variants in *NEK10* were first identified in 2020 (PMID: 31959991). The mutational spectrum of disease-causing variants suggests loss of function (LOF) as a mechanism of disease. However, missense and a non-canonical splice variants (p.Pro748Leu, p.Arg773Cys, c.1230+5G>C) have also been identified in the homozygous state. Variant-specific functional studies of cultured patient bronchial epithelial cells in an air-liquid interface reveal short airway cilia in imaging flow cytometry, supporting a deleterious effect. At the same time, many of the individuals in the literature were reported to have normal nasal nitric oxide measurements, normal electron microscopy of the cilia, and absence of abdominal situs abnormalities (PMID: 31959991, 32414360, 33875846, 35728977, 37998386). Experimental evidence supporting this gene-disease relationship includes studies demonstrating that NEK10 protein localizes to motile cilia and interacts with other motile cilia proteins, as well as knockout/knockdown assays in cell culture and zebrafish models that result in ciliary abnormalities and can be rescued with exogenous *NEK10* (PMID: 29581457, 31959991). In summary, *NEK10* has a Definitive association with primary ciliary dyskinesia 44 based on multiple genetic and experimental evidence data points. This has been repeatedly demonstrated in both research and diagnostic settings and has been upheld over time without the emergence of contradictory evidence. This classification was approved by the ClinGen Motile Ciliopathy GCEP on July 10, 2025 (SOP Version 11).

ciliary dyskinesia, primary, 44STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032914

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ciliary dyskinesia, primary, 44AR

Manifestation: Allergy/Immunology/Infectious; Pulmonary

Intervention: Allergy/Immunology/Infectious; Pulmonary

Rationale: Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial

Refs: 20301301; 31959991

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NEK10 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 24

Ciliary dyskinesia, primary, 44Total: 15

NEK10-related disorderTotal: 2

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394966.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar		6
missense	3 clinvar	1 clinvar	78 clinvar	4 clinvar	3 clinvar	89
nonsense		2 clinvar				2
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)		3 clinvar	2 clinvar			5
Total	6	7	80	10	3	106

Highest pathogenic variant AF is 0.000021190957

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394966.1	RefSeq	NP_001381895.1	35	MANE Select
ENST00000691995.1	Ensembl	ENSP00000509472.1	35	MANE Select
NM_001031741.5	RefSeq	NP_001026911.1	15	Standard
NM_001304384.3	RefSeq	NP_001291313.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
positive regulation of protein autophosphorylation
positive regulation of MAP kinase activity
regulation of ERK1 and ERK2 cascade
regulation of cell cycle G2/M phase transition

Molecular Function

protein kinase activity
protein serine/threonine kinase activity
ATP binding
metal ion binding

Cellular Component

protein kinase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341435
Coding exons: 23
Length: 259376
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125747
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.616	325	358	0.908	0.0000178	4685
Missense (PolyPhen)		81	111.79	0.72457		1526
Synonymous	0.733	115	125	0.917	0.00000638	1263
Loss of Function	2.91	22	42.4	0.518	0.00000215	550

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0.00027	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0824

Intolerance Scores

LoFtool: 0.655
RVIS EVS: 0.89
RVIS percentile EVS: 89.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.675

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium