Primary ciliary dyskinesia 25

Summary

Primary ciliary dyskinesia 25 (MONDO:0014203) is a disease caused by DNAAF4 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: DNAAF4 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 25
Mondo ID	MONDO:0014203
OMIM	615482
DOID	DOID:0110615
UMLS	C3809641
MedGen	815971
GARD	0015972
Is cancer (heuristic)	no

Also known as: CILD25 · ciliary dyskinesia, primary, 25 · ciliary dyskinesia, primary, type 25 · DNAAF4 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DNAAF4 · primary ciliary dyskinesia type 25

Data availability: 26 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 25

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 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

26 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 6 pathogenic, 5 pathogenic/likely pathogenic, 3 likely pathogenic, 2 benign, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2500780	NM_130810.4(DNAAF4):c.784_893del (p.Trp262fs)	DNAAF4	Pathogenic	criteria provided, single submitter
496919	NM_001033560.1(DNAAF4):c.523dup (p.Ile175Asnfs)	DNAAF4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
505757	NM_130810.4(DNAAF4):c.523del (p.Ile175fs)	DNAAF4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
577768	NM_130810.4(DNAAF4):c.583del (p.Lys194_Ile195insTer)	DNAAF4	Pathogenic	criteria provided, multiple submitters, no conflicts
68448	NM_130810.4(DNAAF4):c.808C>T (p.Arg270Ter)	DNAAF4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68449	NM_130810.4(DNAAF4):c.325G>T (p.Glu109Ter)	DNAAF4	Pathogenic	criteria provided, multiple submitters, no conflicts
869382	NM_130810.4(DNAAF4):c.589_593del (p.Tyr197fs)	DNAAF4	Pathogenic	criteria provided, multiple submitters, no conflicts
916125	NM_130810.4(DNAAF4):c.784-1037_894-2012del	DNAAF4	Pathogenic	criteria provided, multiple submitters, no conflicts
2575241	NM_130810.4(DNAAF4):c.390_393del (p.Ser131_Val132insTer)	DNAAF4-CCPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
525326	NM_130810.4(DNAAF4):c.31C>T (p.Gln11Ter)	DNAAF4-CCPG1	Pathogenic	criteria provided, multiple submitters, no conflicts
956594	NM_130810.4(DNAAF4):c.988C>T (p.Arg330Trp)	DNAAF4-CCPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779571	NM_130810.4(DNAAF4):c.81C>A (p.Cys27Ter)	DNAAF4	Likely pathogenic	criteria provided, single submitter
4081337	NM_130810.4(DNAAF4):c.168del (p.Pro56_Ile57insTer)	DNAAF4	Likely pathogenic	criteria provided, single submitter
804473	NM_130810.4(DNAAF4):c.384_390del (p.Lys127_Tyr128insTer)	DNAAF4	Likely pathogenic	criteria provided, single submitter
3711699	NM_130810.4(DNAAF4):c.583dup (p.Ile195fs)	DNAAF4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
525327	NM_130810.4(DNAAF4):c.56T>A (p.Leu19Gln)	DNAAF4-CCPG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2440895	NM_130810.4(DNAAF4):c.59C>G (p.Ser20Cys)	DNAAF4	Uncertain significance	criteria provided, single submitter
410958	NM_130810.4(DNAAF4):c.1241A>C (p.Gln414Pro)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
410961	NM_130810.4(DNAAF4):c.791A>G (p.His264Arg)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
571153	NM_130810.4(DNAAF4):c.454C>T (p.Arg152Trp)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
578519	NM_130810.4(DNAAF4):c.4C>T (p.Pro2Ser)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
846505	NM_130810.4(DNAAF4):c.246G>C (p.Met82Ile)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
853435	NM_130810.4(DNAAF4):c.402G>A (p.Met134Ile)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
964667	NM_130810.4(DNAAF4):c.829A>G (p.Ile277Val)	DNAAF4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2136	NM_130810.4(DNAAF4):c.1249G>T (p.Glu417Ter)	DNAAF4	Benign	criteria provided, multiple submitters, no conflicts
262315	NM_130810.4(DNAAF4):c.572A>G (p.Glu191Gly)	DNAAF4	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
DNAAF4	Definitive	Autosomal recessive	primary ciliary dyskinesia 25	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF4	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAAF4	HGNC:21493	ENSG00000256061	Q8WXU2	Dynein axonemal assembly factor 4	gencc,clinvar
DNAAF4-CCPG1	HGNC:43019	ENSG00000261771		DNAAF4-CCPG1 readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF4	Dynein axonemal assembly factor 4	Axonemal dynein assembly factor required for ciliary motility.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF4	Other/Unknown	no		CS_dom, HSP20-like_chaperone, TPR-like_helical_dom_sf
DNAAF4-CCPG1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
secondary oocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF4	188	ubiquitous	marker	bronchial epithelial cell, bronchus, secondary oocyte
DNAAF4-CCPG1	115	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAAF4	1,742
DNAAF4-CCPG1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAAF4	Q8WXU2	84.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
regulation of intracellular estrogen receptor signaling pathway	1	1872.4×	0.003	DNAAF4
inner dynein arm assembly	1	887.0×	0.003	DNAAF4
epithelial cilium movement involved in extracellular fluid movement	1	766.0×	0.003	DNAAF4
regulation of proteasomal protein catabolic process	1	766.0×	0.003	DNAAF4
outer dynein arm assembly	1	732.7×	0.003	DNAAF4
cilium movement	1	391.9×	0.005	DNAAF4
determination of left/right symmetry	1	255.3×	0.006	DNAAF4
learning or memory	1	240.7×	0.006	DNAAF4
establishment of localization in cell	1	160.5×	0.008	DNAAF4
neuron migration	1	133.8×	0.008	DNAAF4
heart development	1	78.8×	0.013	DNAAF4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
DNAAF4	0	0
DNAAF4-CCPG1	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	2	DNAAF4, DNAAF4-CCPG1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAAF4	0	—
DNAAF4-CCPG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.