Primary ciliary dyskinesia 10

Summary

Primary ciliary dyskinesia 10 (MONDO:0012918) is a disease caused by DNAAF2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DNAAF2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 93

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 10
Mondo ID	MONDO:0012918
MeSH	C567287
OMIM	612518
DOID	DOID:0110612
UMLS	C2675867
MedGen	382707
GARD	0015560
Is cancer (heuristic)	no

Also known as: CILD10 · ciliary dyskinesia, primary, 10 · ciliary dyskinesia, primary, type 10 · DNAAF2 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DNAAF2 · primary ciliary dyskinesia type 10

Data availability: 93 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 › primary ciliary dyskinesia 10

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 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, 44, 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

93 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 28 conflicting classifications of pathogenicity, 9 benign, 9 benign/likely benign, 6 pathogenic, 4 likely pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1189037	NM_018139.3(DNAAF2):c.26C>A (p.Ser9Ter)	DNAAF2	Pathogenic	no assertion criteria provided
1189038	NM_018139.3(DNAAF2):c.156C>A (p.Tyr52Ter)	DNAAF2	Pathogenic	no assertion criteria provided
1322750	NM_018139.3(DNAAF2):c.476dup (p.Phe160fs)	DNAAF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2039186	NM_018139.3(DNAAF2):c.1510C>T (p.Gln504Ter)	DNAAF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208847	NM_018139.3(DNAAF2):c.1199_1214dup (p.Gly406fs)	DNAAF2	Pathogenic	no assertion criteria provided
411172	NM_018139.3(DNAAF2):c.1156_1159dup (p.Glu387fs)	DNAAF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
529	NM_018139.3(DNAAF2):c.23C>A (p.Ser8Ter)	DNAAF2	Pathogenic	no assertion criteria provided
2442010	NM_018139.3(DNAAF2):c.1054_1087del (p.Ala352fs)	LOC130055542	Pathogenic	criteria provided, single submitter
179361	NM_018139.3(DNAAF2):c.727G>T (p.Glu243Ter)	DNAAF2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2683949	NM_018139.3(DNAAF2):c.1807G>T (p.Glu603Ter)	DNAAF2	Likely pathogenic	criteria provided, single submitter
3234972	NM_018139.3(DNAAF2):c.751dup (p.Thr251fs)	DNAAF2	Likely pathogenic	criteria provided, single submitter
4081335	NM_018139.3(DNAAF2):c.1495dup (p.Glu499fs)	DNAAF2	Likely pathogenic	criteria provided, single submitter
193393	NM_018139.3(DNAAF2):c.1584T>A (p.Asn528Lys)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195338	NM_018139.3(DNAAF2):c.1953A>G (p.Pro651=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216703	NM_018139.3(DNAAF2):c.1417C>T (p.Arg473Trp)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216704	NM_018139.3(DNAAF2):c.20C>T (p.Ser7Phe)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227314	NM_018139.3(DNAAF2):c.423C>T (p.Val141=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228602	NM_018139.3(DNAAF2):c.1463G>A (p.Gly488Glu)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228604	NM_018139.3(DNAAF2):c.1595A>G (p.Glu532Gly)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241280	NM_018139.3(DNAAF2):c.1405T>A (p.Cys469Ser)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241283	NM_018139.3(DNAAF2):c.824C>T (p.Ala275Val)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261013	NM_018139.3(DNAAF2):c.1494G>A (p.Ser498=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261019	NM_018139.3(DNAAF2):c.384C>A (p.Gly128=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313275	NM_018139.3(DNAAF2):c.2388C>T (p.His796=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313277	NM_018139.3(DNAAF2):c.1687G>T (p.Ala563Ser)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313279	NM_018139.3(DNAAF2):c.1315G>C (p.Asp439His)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313282	NM_018139.3(DNAAF2):c.734C>T (p.Ala245Val)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313283	NM_018139.3(DNAAF2):c.731C>A (p.Ala244Glu)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313286	NM_018139.3(DNAAF2):c.471C>T (p.His157=)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313289	NM_018139.3(DNAAF2):c.263G>A (p.Cys88Tyr)	DNAAF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
DNAAF2	Strong	Autosomal recessive	primary ciliary dyskinesia 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF2	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
DNAAF2	HGNC:20188	ENSG00000165506	Q9NVR5	Protein kintoun	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF2	Protein kintoun	Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF2	Other/Unknown	no		PIH1_N, Kintoun, PIH1D1/2/3_CS-like

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
bronchial epithelial cell	1
epithelium of bronchus	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF2	273	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAAF2	999

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAAF2	Q9NVR5	65.57

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
establishment of left/right asymmetry	1	2106.5×	0.002	DNAAF2
cilium-dependent cell motility	1	1404.3×	0.002	DNAAF2
axonemal dynein complex assembly	1	1053.2×	0.002	DNAAF2
inner dynein arm assembly	1	887.0×	0.002	DNAAF2
epithelial cilium movement involved in extracellular fluid movement	1	766.0×	0.002	DNAAF2
outer dynein arm assembly	1	732.7×	0.002	DNAAF2
response to retinoic acid	1	383.0×	0.004	DNAAF2
establishment of localization in cell	1	160.5×	0.008	DNAAF2
in utero embryonic development	1	72.0×	0.015	DNAAF2
protein stabilization	1	66.9×	0.015	DNAAF2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNAAF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DNAAF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAAF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.