DNAAF1

Summary

DNAAF1 (dynein axonemal assembly factor 1, HGNC:30539) is a protein-coding gene on chromosome 16q24.1, encoding Dynein axonemal assembly factor 1 (Q8NEP3). Cilium-specific protein required for the stability of the ciliary architecture.

The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 123872 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 13 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 761 total — 48 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 55
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_178452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30539
Approved symbol	DNAAF1
Name	dynein axonemal assembly factor 1
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25330, ODA7, CILD13, swt, DAU1
Ensembl gene	ENSG00000154099
Ensembl biotype	protein_coding
OMIM	613190
Entrez	123872

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 TEC

ENST00000378553, ENST00000562024, ENST00000563093, ENST00000563818, ENST00000564928, ENST00000567666, ENST00000567918, ENST00000569735, ENST00000570298, ENST00000623406, ENST00000897897, ENST00000963694, ENST00000963695, ENST00000963696, ENST00000963697

RefSeq mRNA: 2 — MANE Select: NM_178452 NM_001318756, NM_178452

CCDS: CCDS10943

Canonical transcript exons

ENST00000378553 — 12 exons

Exon	Start	End
ENSE00002588627	84145308	84145564
ENSE00003477629	84155583	84155749
ENSE00003479010	84175933	84176299
ENSE00003501428	84177729	84177918
ENSE00003508720	84174669	84174722
ENSE00003539881	84150251	84150342
ENSE00003548515	84159675	84159796
ENSE00003574269	84154577	84154798
ENSE00003576580	84172260	84172375
ENSE00003637534	84169859	84170356
ENSE00003661774	84149007	84149142
ENSE00003673678	84165783	84165949

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 99.59.

FANTOM5 (CAGE): breadth broad, TPM avg 9.6989 / max 956.9501, expressed in 399 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155293	8.5114	269
155288	0.6777	146
155292	0.1996	69
155294	0.1351	63
155290	0.0724	36
155291	0.0433	27
155289	0.0421	23
155287	0.0173	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.59	gold quality
bronchial epithelial cell	CL:0002328	99.27	gold quality
epithelium of bronchus	UBERON:0002031	99.24	gold quality
bronchus	UBERON:0002185	98.79	gold quality
left testis	UBERON:0004533	96.66	gold quality
right testis	UBERON:0004534	96.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.62	gold quality
nasal cavity epithelium	UBERON:0005384	94.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.60	gold quality
testis	UBERON:0000473	93.46	gold quality
male germ cell	CL:0000015	93.32	gold quality
sperm	CL:0000019	93.15	gold quality
olfactory bulb	UBERON:0002264	90.18	gold quality
caput epididymis	UBERON:0004358	89.83	gold quality
epithelium of nasopharynx	UBERON:0001951	89.14	gold quality
type B pancreatic cell	CL:0000169	88.25	gold quality
adult organism	UBERON:0007023	87.73	gold quality
fallopian tube	UBERON:0003889	85.34	gold quality
trachea	UBERON:0003126	84.69	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	84.35	gold quality
hypothalamus	UBERON:0001898	84.31	gold quality
pituitary gland	UBERON:0000007	84.30	gold quality
adenohypophysis	UBERON:0002196	83.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.83	gold quality
nasal cavity mucosa	UBERON:0001826	83.39	gold quality
left uterine tube	UBERON:0001303	83.37	gold quality
right lung	UBERON:0002167	83.21	gold quality
caudate nucleus	UBERON:0001873	81.90	gold quality
buccal mucosa cell	CL:0002336	81.85	silver quality
oviduct epithelium	UBERON:0004804	81.59	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	1821.69
E-HCAD-15	yes	1687.11
E-MTAB-10283	yes	1088.47
E-MTAB-6308	yes	1023.13
E-GEOD-86618	yes	49.03
E-HCAD-1	yes	31.13
E-MTAB-10287	yes	27.50
E-CURD-46	yes	21.76
E-GEOD-130148	yes	14.25
E-GEOD-70580	no	53.50
E-MTAB-7303	no	19.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• It is proposed that LRRC50 to be a novel candidate gene for human cystic kidney disease, involved in regulation of microtubule-based cilia and actin-based brush border microvilli (PMID:18385425)
• LRRC50 plays a role in assembly of distinct dynein-arm complexes (PMID:19944400)
• LRRC50, a member of the leucine-rich-repeat superfamily, has a key role in cytoplasmic preassembly of dynein arms (PMID:19944405)
• our findings here demonstrate that mutations in the motile cilia gene DNAAF1 could contribute to the pathogenesis of NTDs. (PMID:27543293)
• The most significantly mutated cilia-microtubule gene in testicular germ cell tumors is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumors from carriers. (PMID:27996046)
• DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport (PMID:29228333)
• DNAAF1 mRNA expression is significantly reduced in the anterior horn in sporadic amyotrophic lateral sclerosis patients. (PMID:30939186)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnaaf1	ENSDARG00000012030
mus_musculus	Dnaaf1	ENSMUSG00000031831
rattus_norvegicus	Dnaaf1	ENSRNOG00000015590
drosophila_melanogaster	dtr	FBGN0023090

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Dynein axonemal assembly factor 1 — Q8NEP3 (reviewed: Q8NEP3)

Alternative names: Leucine-rich repeat-containing protein 50

All UniProt accessions (5): Q8NEP3, A0A140VJN4, H3BNQ4, H3BP51, H3BV09

UniProt curated annotations — full annotation on UniProt →

Function. Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms. Involved in regulation of microtubule-based cilia and actin-based brush border microvilli.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Spindle pole.

Tissue specificity. Mainly expressed in trachea and testis.

Disease relevance. Ciliary dyskinesia, primary, 13 (CILD13) [MIM:613193] 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; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. At ultrastructural level, CILD13 is characterized by a marked reduction or absence of both dynein arms from the patients cilia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DNAAF1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NEP3-1	1	yes
Q8NEP3-2	2
Q8NEP3-3	3

RefSeq proteins (1): NP_848547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050576	Cilia_flagella_integrity	Family

Pfam: PF14580

UniProt features (42 total): sequence variant 13, compositionally biased region 7, repeat 6, modified residue 4, sequence conflict 4, region of interest 3, splice variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEP3-F1	61.56	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 358, 559, 562, 583

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_PANCREAS_DEVELOPMENT, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_INNER_DYNEIN_ARM_ASSEMBLY, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_HEART_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION

GO Biological Process (15): heart looping (GO:0001947), cilium movement (GO:0003341), regulation of cilium beat frequency (GO:0003356), lung development (GO:0030324), axoneme assembly (GO:0035082), determination of pancreatic left/right asymmetry (GO:0035469), outer dynein arm assembly (GO:0036158), inner dynein arm assembly (GO:0036159), motile cilium assembly (GO:0044458), cilium assembly (GO:0060271), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), left/right pattern formation (GO:0060972), axonemal dynein complex assembly (GO:0070286), determination of digestive tract left/right asymmetry (GO:0071907), determination of liver left/right asymmetry (GO:0071910)

GO Molecular Function (2): dynein complex binding (GO:0070840), protein binding (GO:0005515)

GO Cellular Component (7): spindle pole (GO:0000922), extracellular region (GO:0005576), cytoplasm (GO:0005737), axoneme (GO:0005930), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
determination of left/right symmetry	4
cilium assembly	2
axonemal dynein complex assembly	2
axoneme assembly	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
microtubule-based movement	1
regulation of cilium movement	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
microtubule bundle formation	1
cellular component assembly	1
pancreas development	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
epithelial cilium movement involved in extracellular fluid movement	1
regionalization	1
protein-containing complex assembly	1
digestive tract development	1
liver development	1
protein-containing complex binding	1
binding	1
spindle	1
intracellular anatomical structure	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAAF1	DNAI2	Q9GZS0	982
DNAAF1	DNALI1	O14645	966
DNAAF1	DNAH5	Q8TE73	961
DNAAF1	RSPH4A	Q5TD94	940
DNAAF1	DNAAF2	Q9NVR5	939
DNAAF1	DNAI1	Q9UI46	939
DNAAF1	RSPH9	Q9H1X1	925
DNAAF1	DNAH11	Q96DT5	899
DNAAF1	DNAAF3	Q8N9W5	886
DNAAF1	NME8	Q8N427	877
DNAAF1	CFAP298	P57076	871
DNAAF1	DNAAF4	Q8WXU2	860
DNAAF1	ZMYND10	O75800	821
DNAAF1	DNAAF5	Q86Y56	813
DNAAF1	CCDC40	Q4G0X9	813

IntAct

10 interactions, top by confidence:

A	B	Type	Score
DNAAF1	OBSL1	psi-mi:“MI:0914”(association)	0.510
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
XPNPEP3	SEC16A	psi-mi:“MI:0914”(association)	0.510
FADD	NUP42	psi-mi:“MI:0914”(association)	0.350
DNAAF1	STOM	psi-mi:“MI:0915”(physical association)	0.000
DNAAF1	ANKMY2	psi-mi:“MI:0915”(physical association)	0.000
OBSL1	DNAAF1	psi-mi:“MI:0915”(physical association)	0.000
GLRX3	DNAAF1	psi-mi:“MI:0915”(physical association)	0.000
XPNPEP3	DNAAF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): DNAAF1 (Affinity Capture-MS), DNAAF1 (Affinity Capture-MS), ANKMY2 (Affinity Capture-MS), DNAAF1 (Affinity Capture-MS), STOM (Affinity Capture-MS), DNAAF1 (Affinity Capture-MS), DNAAF1 (Synthetic Lethality), DNAAF1 (Proximity Label-MS), DNAAF1 (Affinity Capture-RNA), DNAAF1 (Affinity Capture-MS), DNAAF1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8I5ZN27, A6X8Z5, E1AZ71, F1N8V3, O35668, O54963, O70318, P20689, P48165, P51954, P54256, P54257, P55917, P62025, P70278, Q01538, Q13029, Q13127, Q14028, Q16799, Q28139, Q28181, Q2M1Z3, Q3SYS4, Q3UH66, Q4KMM3, Q4V8B0, Q5DW34, Q5IS59, Q5TCY1, Q62100, Q63HN8, Q640N3, Q64548, Q6IR42, Q6PCN3, Q7Z6I6, Q811Q2, Q8BYM7, Q8C5W0

Diamond homologs: B3NLX1, B4GT53, B4P6W7, B6D5P1, B6D5P3, B6D5P6, Q09JZ4, Q16RY9, Q29KL8, Q3SYS4, Q6AYH9, Q7PK92, Q7ZV84, Q8INT5, Q8NEP3, Q9D2H9, B6CZ45, B6CZ54, B6CZ61, P34390, Q1X8D7, Q3V0M2, Q5EAD8, Q9D3R3, Q9DAK8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	9
Uncertain significance	338
Likely benign	210
Benign	77

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012299	NM_178452.6(DNAAF1):c.1496del (p.Pro499fs)	Pathogenic
1012300	NM_178452.6(DNAAF1):c.1930A>T (p.Arg644Ter)	Pathogenic
1069363	NM_178452.6(DNAAF1):c.922C>T (p.Gln308Ter)	Pathogenic
1076147	NC_000016.9:g.(?84182606)(84211452_?)del	Pathogenic
1344596	NM_178452.6(DNAAF1):c.778C>T (p.Gln260Ter)	Pathogenic
1453545	NM_178452.6(DNAAF1):c.1957G>T (p.Glu653Ter)	Pathogenic
1457184	NC_000016.9:g.(?84179046)(84193421_?)del	Pathogenic
1730182	NM_178452.6(DNAAF1):c.331dup (p.Thr111fs)	Pathogenic
1905629	NM_178452.6(DNAAF1):c.1618G>T (p.Glu540Ter)	Pathogenic
2027246	NM_178452.6(DNAAF1):c.317del (p.Pro106fs)	Pathogenic
2048027	NM_178452.6(DNAAF1):c.30del (p.Gly11fs)	Pathogenic
2137852	NM_178452.6(DNAAF1):c.1462C>T (p.Arg488Ter)	Pathogenic
2152858	NM_178452.6(DNAAF1):c.1606del (p.Thr536fs)	Pathogenic
2160990	NM_178452.6(DNAAF1):c.649C>T (p.Gln217Ter)	Pathogenic
2166548	NM_178452.6(DNAAF1):c.58C>T (p.Gln20Ter)	Pathogenic
2427569	NC_000016.9:g.(?84193260)(84193421_?)del	Pathogenic
2427570	NC_000016.9:g.(?84188162)(84203982_?)del	Pathogenic
263	NM_178452.6(DNAAF1):c.1349dup (p.Pro451fs)	Pathogenic
264	NM_178452.6(DNAAF1):c.811C>T (p.Arg271Ter)	Pathogenic
265	NM_178452.6(DNAAF1):c.792C>A (p.Tyr264Ter)	Pathogenic
266	NM_178452.6(DNAAF1):c.508dup (p.Glu170fs)	Pathogenic
267	NM_178452.6(DNAAF1):c.524T>G (p.Leu175Arg)	Pathogenic
2693009	NM_178452.6(DNAAF1):c.205_212del (p.Gly69fs)	Pathogenic
2777500	NM_178452.6(DNAAF1):c.442G>T (p.Glu148Ter)	Pathogenic
2867981	NM_178452.6(DNAAF1):c.1525G>T (p.Glu509Ter)	Pathogenic
2915325	NM_178452.6(DNAAF1):c.462_465del (p.Cys155fs)	Pathogenic
2981110	NM_178452.6(DNAAF1):c.1746dup (p.Ser583fs)	Pathogenic
3004708	NM_178452.6(DNAAF1):c.1435del (p.Pro478_Val479insTer)	Pathogenic
3243218	NC_000016.9:g.(?84179046)(84211465_?)del	Pathogenic
3243219	NC_000016.9:g.(?84199369)(84199575_?)del	Pathogenic

SpliceAI

2437 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84145561:G:GT	donor_gain	1.0000
16:84145562:A:T	donor_gain	1.0000
16:84149126:G:T	donor_gain	1.0000
16:84150249:A:AG	acceptor_gain	1.0000
16:84150250:G:GG	acceptor_gain	1.0000
16:84150250:GAAT:G	acceptor_gain	1.0000
16:84154794:CCTCT:C	donor_gain	1.0000
16:84154799:G:GG	donor_gain	1.0000
16:84155702:C:G	donor_gain	1.0000
16:84155733:A:T	donor_gain	1.0000
16:84159673:A:AG	acceptor_gain	1.0000
16:84159674:G:GA	acceptor_gain	1.0000
16:84159674:GC:G	acceptor_gain	1.0000
16:84159674:GCGT:G	acceptor_gain	1.0000
16:84159794:CAGG:C	donor_loss	1.0000
16:84159795:AGGTA:A	donor_loss	1.0000
16:84159796:GGTAA:G	donor_loss	1.0000
16:84159797:G:GA	donor_loss	1.0000
16:84159798:T:A	donor_loss	1.0000
16:84162130:A:AG	acceptor_gain	1.0000
16:84162131:G:GG	acceptor_gain	1.0000
16:84170353:G:T	donor_gain	1.0000
16:84172382:G:GT	donor_gain	1.0000
16:84172397:GGAGA:G	donor_gain	1.0000
16:84172398:GAGA:G	donor_gain	1.0000
16:84145535:G:GT	donor_gain	0.9900
16:84145583:G:GT	donor_gain	0.9900
16:84147018:TTC:T	donor_gain	0.9900
16:84149001:TTACA:T	acceptor_loss	0.9900
16:84149002:TACA:T	acceptor_loss	0.9900

AlphaMissense

4751 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84154773:T:A	N183K	0.999
16:84154773:T:G	N183K	0.999
16:84155623:T:A	N205K	0.998
16:84155623:T:G	N205K	0.998
16:84154631:T:C	L136P	0.997
16:84154641:T:A	N139K	0.997
16:84154641:T:G	N139K	0.997
16:84154707:C:A	N161K	0.997
16:84154707:C:G	N161K	0.997
16:84154757:T:A	L178H	0.997
16:84154757:T:C	L178P	0.997
16:84155688:T:C	L227P	0.997
16:84155698:C:A	N230K	0.997
16:84155698:C:G	N230K	0.997
16:84159682:T:C	L250P	0.997
16:84159698:C:A	N255K	0.997
16:84159698:C:G	N255K	0.997
16:84159766:T:C	L278P	0.997
16:84165796:G:C	A293P	0.997
16:84150317:T:A	N109K	0.996
16:84150317:T:G	N109K	0.996
16:84155682:T:A	L225H	0.996
16:84154625:T:A	L134H	0.995
16:84154625:T:C	L134P	0.995
16:84154691:T:C	L156P	0.995
16:84154772:A:T	N183I	0.995
16:84155682:T:C	L225P	0.995
16:84159727:G:C	R265T	0.995
16:84159728:A:C	R265S	0.995
16:84159728:A:T	R265S	0.995

dbSNP variants (sampled 300 via entrez): RS1000028233 (16:84144293 G>C), RS1000032474 (16:84153950 C>T), RS1000058510 (16:84162647 C>G), RS1000080122 (16:84176479 C>G,T), RS1000097794 (16:84154289 A>G), RS1000123563 (16:84169946 A>C), RS1000183780 (16:84165210 T>G), RS1000257407 (16:84165513 G>A), RS1000275327 (16:84160585 C>A,G), RS1000321871 (16:84145881 C>G,T), RS1000409875 (16:84160808 G>A), RS1000559913 (16:84169469 G>C), RS1000577790 (16:84167790 T>G), RS1000581275 (16:84169162 C>T), RS1000582025 (16:84156508 C>G)

Disease associations

OMIM: gene MIM:613190 | disease phenotypes: MIM:613193, MIM:244400

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 13	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
primary ciliary dyskinesia 13	Definitive	AR

Mondo (3): primary ciliary dyskinesia 13 (MONDO:0013174), primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 1 (MONDO:0009484)

Orphanet (3): Primary ciliary dyskinesia (Orphanet:244), Situs ambiguus (Orphanet:157769), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

55 total (30 of 55 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: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:0000789	Infertility
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:0002837	Recurrent bronchitis
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003264_254	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003807_9	Systolic blood pressure response to hydrochlorothiazide in hypertension	3.000000e-07
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0006944	systolic blood pressure change measurement
EFO:0007943	response to platinum-based neoadjuvant chemotherapy

MeSH disease descriptors (3)

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
C567713	Ciliary Dyskinesia, Primary, 13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
TL8-506	affects cotreatment, increases expression	1
2,3-pentanedione	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
gardiquimod	increases expression, decreases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Diacetyl	decreases expression	1
Estradiol	affects cotreatment, decreases expression, increases expression	1
Ivermectin	decreases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

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)