Ciliary dyskinesia, primary, 44

Summary

Ciliary dyskinesia, primary, 44 (MONDO:0032914) is a disease caused by NEK10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NEK10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ciliary dyskinesia, primary, 44
Mondo ID	MONDO:0032914
OMIM	618781
DOID	DOID:0111851
UMLS	C5394063
MedGen	1716408
GARD	0016380
Is cancer (heuristic)	no

Also known as: CILD44

Data availability: 21 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › ciliary dyskinesia, primary, 44

Related subtypes (58): ciliary discoordination due to random ciliary orientation, ciliary dyskinesia with transposition of ciliary microtubules, ciliary dyskinesia with defective radial spokes, ciliary dyskinesia with excessively long cilia, Stromme syndrome, primary ciliary dyskinesia 1, ciliary dyskinesia, primary, 36, X-linked, primary ciliary dyskinesia 2, primary ciliary dyskinesia 3, primary ciliary dyskinesia 4, primary ciliary dyskinesia 5, primary ciliary dyskinesia 6, primary ciliary dyskinesia 7, primary ciliary dyskinesia 8, primary ciliary dyskinesia 9, primary ciliary dyskinesia 10, primary ciliary dyskinesia 11, primary ciliary dyskinesia 12, primary ciliary dyskinesia 13, primary ciliary dyskinesia 14, primary ciliary dyskinesia 15, primary ciliary dyskinesia 16, primary ciliary dyskinesia 17, primary ciliary dyskinesia 18, primary ciliary dyskinesia 19, primary ciliary dyskinesia 20, primary ciliary dyskinesia 21, primary ciliary dyskinesia 22, primary ciliary dyskinesia 23, primary ciliary dyskinesia 24, primary ciliary dyskinesia 25, primary ciliary dyskinesia 26, primary ciliary dyskinesia 27, primary ciliary dyskinesia 28, primary ciliary dyskinesia 29, primary ciliary dyskinesia 30, primary ciliary dyskinesia 32, primary ciliary dyskinesia 33, primary ciliary dyskinesia 34, primary ciliary dyskinesia 35, ciliary dyskinesia, primary, 46, ciliary dyskinesia, primary, 47, and lissencephaly, ciliary dyskinesia, primary, 48, without situs inversus, ciliary dyskinesia, primary, 39, ciliary dyskinesia, primary, 40, ciliary dyskinesia, primary, 41, ciliary dyskinesia, primary, 42, ciliary dyskinesia, primary, 43, ciliary dyskinesia, primary, 45, ciliary dyskinesia, primary, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, ciliary dyskinesia, primary, 50, ciliary dyskinesia, primary, 51, ciliary dyskinesia, primary, 52, ciliary dyskinesia, primary, 53, CFAP46-related primary ciliary dyskinesia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

21 retrieved; paginated sample, class counts are floors:

9 benign, 4 pathogenic, 4 likely pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705354	NM_001394966.1(NEK10):c.1154dup (p.Ser386fs)	NEK10	Pathogenic	criteria provided, single submitter
813279	NM_001394966.1(NEK10):c.1869dup (p.His624fs)	NEK10	Pathogenic	no assertion criteria provided
813280	NM_001394966.1(NEK10):c.2243C>T (p.Pro748Leu)	NEK10	Pathogenic	no assertion criteria provided
813281	NM_001394966.1(NEK10):c.2317C>T (p.Arg773Cys)	NEK10	Pathogenic	no assertion criteria provided
3064479	NM_001394966.1(NEK10):c.2182C>T (p.Pro728Ser)	NEK10	Likely pathogenic	criteria provided, single submitter
4081549	NM_001394966.1(NEK10):c.489+1G>A	NEK10	Likely pathogenic	criteria provided, single submitter
4849299	NM_001394966.1(NEK10):c.975_976insTGAGAAT (p.Val326Ter)	NEK10	Likely pathogenic	criteria provided, single submitter
813278	NM_001394966.1(NEK10):c.1230+5G>C	NEK10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2575401	NM_001394966.1(NEK10):c.3282C>A (p.Tyr1094Ter)	NEK10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3235018	NM_001394966.1(NEK10):c.382C>T (p.Pro128Ser)	NEK10	Uncertain significance	criteria provided, single submitter
3235019	NM_001394966.1(NEK10):c.2754C>A (p.Ser918Arg)	NEK10	Uncertain significance	criteria provided, single submitter
4293770	NM_001394966.1(NEK10):c.998G>T (p.Gly333Val)	NEK10	Uncertain significance	criteria provided, single submitter
1325890	NM_001394966.1(NEK10):c.2869+140C>T	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325891	NM_001394966.1(NEK10):c.2505+22G>T	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325892	NM_001394966.1(NEK10):c.2247C>G (p.Val749=)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325893	NM_001394966.1(NEK10):c.2061C>G (p.Thr687=)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325894	NM_001394966.1(NEK10):c.2010C>A (p.Thr670=)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325895	NM_001394966.1(NEK10):c.1791T>C (p.Asn597=)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325896	NM_001394966.1(NEK10):c.1674A>G (p.Gly558=)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325897	NM_001394966.1(NEK10):c.1538T>C (p.Leu513Ser)	NEK10	Benign	criteria provided, multiple submitters, no conflicts
1325898	NM_001394966.1(NEK10):c.-37-9A>C	NEK10	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NEK10	Strong	Autosomal recessive	ciliary dyskinesia, primary, 44	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEK10	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NEK10	HGNC:18592	ENSG00000163491	Q6ZWH5	Serine/threonine-protein kinase Nek10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEK10	Serine/threonine-protein kinase Nek10	Plays a role in the cellular response to UV irradiation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEK10	Kinase	yes		Prot_kinase_dom, Tyr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEK10	178	broad	marker	olfactory segment of nasal mucosa, right uterine tube, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEK10	1,276

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEK10	Q6ZWH5	70.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of protein autophosphorylation	1	4213.0×	0.001	NEK10
regulation of cell cycle G2/M phase transition	1	2407.4×	0.001	NEK10
mucociliary clearance	1	1296.3×	0.002	NEK10
positive regulation of MAP kinase activity	1	648.1×	0.002	NEK10
regulation of ERK1 and ERK2 cascade	1	581.1×	0.002	NEK10
protein phosphorylation	1	68.0×	0.015	NEK10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK10	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEROCICLIB	3	NEK10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NEK10	40	Binding:40

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LEROCICLIB	3	NEK10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	NEK10
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.