RSPH1

Summary

RSPH1 (radial spoke head component 1, HGNC:12371) is a protein-coding gene on chromosome 21q22.3, encoding Radial spoke head 1 homolog (Q8WYR4). Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.

This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 89765 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 24 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 264 total — 17 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_080860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12371
Approved symbol	RSPH1
Name	radial spoke head component 1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32753, RSP44, RSPH10A, CILD24
Ensembl gene	ENSG00000160188
Ensembl biotype	protein_coding
OMIM	609314
Entrez	89765

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000291536, ENST00000398352, ENST00000493019, ENST00000856517, ENST00000856518, ENST00000856519, ENST00000856520, ENST00000856521, ENST00000936949

RefSeq mRNA: 2 — MANE Select: NM_080860 NM_001286506, NM_080860

CCDS: CCDS13688, CCDS68210

Canonical transcript exons

ENST00000291536 — 9 exons

Exon	Start	End
ENSE00001109809	42485669	42485804
ENSE00001109814	42486371	42486461
ENSE00001327702	42496133	42496224
ENSE00003467057	42492966	42493079
ENSE00003488576	42477291	42477444
ENSE00003493888	42475898	42476047
ENSE00003590447	42482637	42482708
ENSE00003642321	42492758	42492863
ENSE00003645485	42472486	42472870

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 99.74.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2950 / max 395.0038, expressed in 430 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190631	1.6992	342
190632	0.4461	163
190633	0.1497	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.74	gold quality
bronchus	UBERON:0002185	99.62	gold quality
right uterine tube	UBERON:0001302	99.38	gold quality
oviduct epithelium	UBERON:0004804	98.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.03	gold quality
sperm	CL:0000019	96.05	gold quality
trachea	UBERON:0003126	95.68	gold quality
epithelium of nasopharynx	UBERON:0001951	95.67	gold quality
pancreatic ductal cell	CL:0002079	95.58	gold quality
caput epididymis	UBERON:0004358	94.18	gold quality
fallopian tube	UBERON:0003889	93.38	gold quality
nasal cavity epithelium	UBERON:0005384	92.59	gold quality
pituitary gland	UBERON:0000007	90.52	gold quality
left testis	UBERON:0004533	90.31	gold quality
endothelial cell	CL:0000115	90.24	gold quality
caudate nucleus	UBERON:0001873	90.17	gold quality
nucleus accumbens	UBERON:0001882	90.12	gold quality
right testis	UBERON:0004534	89.62	gold quality
superior vestibular nucleus	UBERON:0007227	89.58	gold quality
adenohypophysis	UBERON:0002196	89.57	gold quality
hypothalamus	UBERON:0001898	88.71	gold quality
testis	UBERON:0000473	88.23	gold quality
putamen	UBERON:0001874	87.50	gold quality
oocyte	CL:0000023	85.90	gold quality
amygdala	UBERON:0001876	85.74	gold quality
lateral globus pallidus	UBERON:0002476	85.59	gold quality
adult organism	UBERON:0007023	84.93	gold quality
medial globus pallidus	UBERON:0002477	84.57	gold quality
secondary oocyte	CL:0000655	84.40	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	2442.84
E-HCAD-15	yes	2165.74
E-CURD-114	yes	1953.16
E-MTAB-6653	yes	1655.24
E-GEOD-130148	yes	1425.18
E-MTAB-10287	yes	1000.23
E-MTAB-9154	yes	964.06
E-MTAB-6308	yes	951.75
E-HCAD-1	yes	33.57
E-MTAB-9388	yes	7.45
E-GEOD-99795	no	12.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MNT, RARB

miRNA regulators (miRDB)

12 targeting RSPH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-4445-5P	97.21	66.16	832

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• Radial spoke protein 44 denotes the restricted localization of the protein to the radial spokes of the axonemes of both sperm and cilia. (PMID:17451891)
• RSPH1 mutations thus appear as a major etiology for primary ciliary dyskinesia phenotype. (PMID:23993197)
• Milder disease in patients with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in primary ciliary dyskinesia, suggesting that mutations in RSPH1 may be associated with residual ciliary function. (PMID:24568568)
• RSPH1 mutations in primary ciliary dyskinesia cause structural defects in the cilia. (PMID:25473808)
• Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia. (PMID:31772028)
• Whole-exome sequencing reveals a combination of extremely rare single-nucleotide polymorphism of DNAH9 and RSPH1 genes in a Japanese fetus with situs viscerum inversus. (PMID:34008076)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	RSPH1	ENSDARG00000102261
mus_musculus	Rsph1	ENSMUSG00000024033
rattus_norvegicus	Rsph1	ENSRNOG00000057862
drosophila_melanogaster	Rsph1	FBGN0032478

Paralogs (7): MORN1 (ENSG00000116151), MORN3 (ENSG00000139714), SETD7 (ENSG00000145391), RSPH10B (ENSG00000155026), RSPH10B2 (ENSG00000169402), ALS2CL (ENSG00000178038), MORN2 (ENSG00000188010)

Protein

Protein identifiers

Radial spoke head 1 homolog — Q8WYR4 (reviewed: Q8WYR4)

Alternative names: Cancer/testis antigen 79, Male meiotic metaphase chromosome-associated acidic protein, Meichroacidin, Testis-specific gene A2 protein

All UniProt accessions (1): Q8WYR4

UniProt curated annotations — full annotation on UniProt →

Function. Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.

Subunit / interactions. Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB. Interacts with RSPH3B. Interacts with RSPH4A. Interacts with RSPH6A. Interacts with DNAH12. Interacts with CFAP65.

Subcellular location. Cytoplasm. Chromosome. Cytoskeleton. Cilium axoneme. Flagellum axoneme.

Tissue specificity. Expressed in trachea, lungs, airway brushings, and testes.

Disease relevance. Ciliary dyskinesia, primary, 24 (CILD24) [MIM:615481] 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. Situs inversus is not observed in CILD24 patients. The disease is caused by variants affecting the gene represented in this entry. RSPH1 mutations result in a primary ciliary diskinesia phenotype with defects of the radial spokes and the axonemal central pair of microtubules.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYR4-1	1	yes
Q8WYR4-2	2

RefSeq proteins (2): NP_001273435, NP_543136* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003409	MORN	Repeat

Pfam: PF02493

UniProt features (14 total): repeat 6, compositionally biased region 3, region of interest 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYR4-F1	74.95	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): GOBP_MALE_GAMETE_GENERATION, MODULE_205, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, chr21q22, GOCC_SPINDLE

GO Biological Process (4): spermatid development (GO:0007286), axoneme assembly (GO:0035082), meiotic cell cycle (GO:0051321), microtubule-based process (GO:0007017)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (18): condensed nuclear chromosome (GO:0000794), outer dense fiber (GO:0001520), radial spoke head (GO:0001535), nucleus (GO:0005634), cytosol (GO:0005829), motile cilium (GO:0031514), sperm flagellum (GO:0036126), meiotic spindle (GO:0072687), radial spoke head 1 (GO:0120336), radial spoke head 3 (GO:0120338), radial spoke (GO:0001534), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), axoneme (GO:0005930), cell projection (GO:0042995), 9+2 motile cilium (GO:0097729)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
radial spoke	2
protein-containing complex	2
radial spoke head	2
intracellular membraneless organelle	2
germ cell development	1
spermatid differentiation	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
cellular process	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
sperm flagellum	1
polymeric cytoskeletal fiber	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cilium	1
9+2 motile cilium	1
spindle	1
radial spoke 1	1
radial spoke 3	1
axoneme	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSPH1	RSPH4A	Q5TD94	933
RSPH1	RSPH9	Q9H1X1	907
RSPH1	RSPH3	Q86UC2	794
RSPH1	ODAD1	Q96M63	787
RSPH1	DNAAF19	Q8IW40	786
RSPH1	ZMYND10	O75800	772
RSPH1	DNAI2	Q9GZS0	751
RSPH1	DRC1	Q96MC2	750
RSPH1	CCDC40	Q4G0X9	749
RSPH1	CCDC39	Q9UFE4	748
RSPH1	DNAH5	Q8TE73	736
RSPH1	DRC4	O95995	733
RSPH1	SPAG1	Q07617	723
RSPH1	DRC2	Q8IXS2	712
RSPH1	DNAH11	Q96DT5	712

IntAct

53 interactions, top by confidence:

A	B	Type	Score
MORN3	RSPH1	psi-mi:“MI:0915”(physical association)	0.780
RSPH1	MORN3	psi-mi:“MI:0915”(physical association)	0.780
FBXO16	CETN3	psi-mi:“MI:0914”(association)	0.530
RSPH1	TSPY2	psi-mi:“MI:0914”(association)	0.350
RSPH6A	ATP2A1	psi-mi:“MI:0914”(association)	0.350
MORN3	RSPH1	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DNER	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	SNRNP70	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	USP9X	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	TUBB2A	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	CCN2	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	SF1	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	CTTN	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	RARB	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	MIA2	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DST	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	POLR2C	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	TUBB2B	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	EIF3D	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DEF8	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DNAJC7	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	KDM4A	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	USP9Y	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	OBSL1	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	GLS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (132): MORN3 (Two-hybrid), RSPH1 (Two-hybrid), RSPH4A (Affinity Capture-MS), METAP2 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), RSPH1 (Affinity Capture-MS), RSPH1 (Affinity Capture-MS), MAPK8IP1 (Two-hybrid), BTBD1 (Two-hybrid), OBSL1 (Two-hybrid), CTAGE5 (Two-hybrid), SEZ6L (Two-hybrid), SRXN1 (Two-hybrid), TUBB (Two-hybrid), WDR17 (Two-hybrid)

ESM2 similar proteins: B6CZ17, B6CZ18, O00423, P10830, P53671, Q05BC3, Q08CH7, Q09537, Q15326, Q1XHL7, Q21029, Q28FE4, Q32KM6, Q32KU3, Q32LL6, Q49HM9, Q4R3N2, Q4R842, Q4V8C3, Q4VBJ9, Q502X0, Q569C2, Q5PPV3, Q5TYQ3, Q5VZ52, Q5ZIJ9, Q622Z7, Q63651, Q641X6, Q6GNY1, Q6IND7, Q6PF18, Q6VTH5, Q7DMA9, Q7Z0G7, Q804S5, Q80SY4, Q86YT6, Q8C5T4, Q8K4M9

Diamond homologs: Q6VTH5, Q8VIG3, Q8WYR4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	5	87.7×	2e-07
Transport of connexons to the plasma membrane	5	87.7×	2e-07
Gap junction trafficking and regulation	5	76.8×	2e-07
Gap junction trafficking	5	76.8×	2e-07
Post-chaperonin tubulin folding pathway	5	76.8×	2e-07
Formation of tubulin folding intermediates by CCT/TriC	5	68.2×	4e-07
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	65.8×	4e-07
Prefoldin mediated transfer of substrate to CCT/TriC	5	63.5×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
microtubule cytoskeleton organization	8	21.6×	9e-07
mitotic cell cycle	5	14.9×	2e-03
neuron migration	5	14.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	6
Uncertain significance	87
Likely benign	93
Benign	32

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1361555	NM_080860.4(RSPH1):c.377G>T (p.Gly126Val)	Pathogenic
1453029	NM_080860.4(RSPH1):c.655del (p.Leu219fs)	Pathogenic
1458564	NC_000021.8:g.(?43892928)(43916296_?)del	Pathogenic
2134672	NM_080860.4(RSPH1):c.634dup (p.Thr212fs)	Pathogenic
2427187	NC_000021.8:g.(?43912848)(43916296_?)del	Pathogenic
2829569	NM_080860.4(RSPH1):c.390C>A (p.Tyr130Ter)	Pathogenic
2996041	NM_080860.4(RSPH1):c.790_791del (p.Met264fs)	Pathogenic
3374756	NM_080860.4(RSPH1):c.544C>T (p.Gln182Ter)	Pathogenic
3667795	NM_080860.4(RSPH1):c.655dup (p.Leu219fs)	Pathogenic
408124	NM_080860.4(RSPH1):c.287dup (p.Asn96fs)	Pathogenic
408130	NM_080860.4(RSPH1):c.573+1_573+17del	Pathogenic
454946	NM_080860.4(RSPH1):c.680dup (p.Pro228fs)	Pathogenic
454950	NM_080860.4(RSPH1):c.727_727+138del	Pathogenic
548598	NM_080860.4(RSPH1):c.315C>G (p.Tyr105Ter)	Pathogenic
66988	NM_080860.4(RSPH1):c.366-3C>A	Pathogenic
66990	NM_080860.4(RSPH1):c.275-2A>C	Pathogenic
945089	NM_080860.4(RSPH1):c.287_305dup (p.His102delinsGlnTer)	Pathogenic
1339557	NM_080860.4(RSPH1):c.637C>T (p.Gln213Ter)	Likely pathogenic
2004962	NM_080860.4(RSPH1):c.502-1G>A	Likely pathogenic
2139564	NM_080860.4(RSPH1):c.376G>A (p.Gly126Ser)	Likely pathogenic
3708674	NM_080860.4(RSPH1):c.365+2T>C	Likely pathogenic
4454712	NM_080860.4(RSPH1):c.54+2T>C	Likely pathogenic
66989	NM_080860.4(RSPH1):c.407_410del (p.Lys136fs)	Likely pathogenic

SpliceAI

1618 predictions. Top by Δscore:

Variant	Effect	Δscore
21:42472866:GTTTC:G	acceptor_gain	1.0000
21:42472867:TTTC:T	acceptor_gain	1.0000
21:42472868:TTC:T	acceptor_gain	1.0000
21:42472869:TC:T	acceptor_gain	1.0000
21:42472870:CC:C	acceptor_gain	1.0000
21:42472871:C:CC	acceptor_gain	1.0000
21:42472871:C:T	acceptor_gain	1.0000
21:42472871:CTGA:C	acceptor_loss	1.0000
21:42472872:T:A	acceptor_loss	1.0000
21:42475879:C:A	donor_gain	1.0000
21:42475896:AC:A	donor_gain	1.0000
21:42475897:CC:C	donor_gain	1.0000
21:42475897:CCCT:C	donor_gain	1.0000
21:42475902:AT:A	donor_gain	1.0000
21:42475924:T:TA	donor_gain	1.0000
21:42475937:C:CA	donor_gain	1.0000
21:42477296:G:C	donor_gain	1.0000
21:42475878:T:TA	donor_gain	0.9900
21:42475892:CCTCA:C	donor_loss	0.9900
21:42475893:CTCAC:C	donor_loss	0.9900
21:42475894:TCACC:T	donor_loss	0.9900
21:42475896:A:AC	donor_gain	0.9900
21:42475896:A:T	donor_loss	0.9900
21:42475897:C:CC	donor_gain	0.9900
21:42475903:T:C	donor_gain	0.9900
21:42475903:T:TA	donor_gain	0.9900
21:42475948:T:TA	donor_gain	0.9900
21:42476045:CAC:C	acceptor_gain	0.9900
21:42476046:AC:A	acceptor_gain	0.9900
21:42476047:CC:C	acceptor_gain	0.9900

AlphaMissense

2029 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:42486387:A:G	W117R	0.999
21:42486387:A:T	W117R	0.999
21:42486456:A:G	W94R	0.999
21:42486456:A:T	W94R	0.999
21:42477391:C:A	W209C	0.998
21:42477391:C:G	W209C	0.998
21:42477393:A:G	W209R	0.998
21:42477393:A:T	W209R	0.998
21:42485749:A:G	W141R	0.998
21:42485749:A:T	W141R	0.998
21:42486454:C:A	W94C	0.998
21:42486454:C:G	W94C	0.998
21:42492826:C:T	G69E	0.998
21:42492975:T:A	R53S	0.998
21:42492975:T:G	R53S	0.998
21:42492998:C:A	G46W	0.998
21:42492998:C:G	G46R	0.998
21:42492998:C:T	G46R	0.998
21:42485695:A:C	Y159D	0.997
21:42485804:C:A	R122S	0.997
21:42485804:C:G	R122S	0.997
21:42486392:C:T	G115E	0.997
21:42486399:A:C	Y113D	0.997
21:42486461:C:T	G92E	0.997
21:42492758:C:G	G92R	0.997
21:42492758:C:T	G92R	0.997
21:42492833:A:C	Y67D	0.997
21:42492863:C:A	G57W	0.997
21:42492997:C:T	G46E	0.997
21:42482682:A:C	F176L	0.996

dbSNP variants (sampled 300 via entrez): RS1000015484 (21:42480380 G>A), RS1000270918 (21:42496793 GA>G), RS1000299483 (21:42494745 G>T), RS1000519041 (21:42493322 C>G), RS1000571336 (21:42493708 G>A,C), RS1000712173 (21:42491295 G>A), RS1001022702 (21:42479005 T>A,C), RS1001053657 (21:42472208 G>A,T), RS1001145191 (21:42497117 C>G), RS1001151204 (21:42477698 T>C), RS1001270212 (21:42477883 T>C), RS1001338730 (21:42481171 C>A,G), RS1001507835 (21:42489526 C>A,T), RS1001635925 (21:42497866 G>A), RS1001694746 (21:42495192 G>C,T)

Disease associations

OMIM: gene MIM:609314 | disease phenotypes: MIM:244400, MIM:615481

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 24	Definitive	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 24	Definitive	AR

Mondo (3): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 24 (MONDO:0014202), primary ciliary dyskinesia 1 (MONDO:0009484)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

54 total (30 of 54 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:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections
HP:0006510	Chronic pulmonary obstruction

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
entinostat	decreases expression, increases expression, affects cotreatment	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Camptothecin	increases expression	1
Catechin	affects cotreatment, increases expression	1
Dactinomycin	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Smoke	increases abundance, increases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	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)