CCNO

Summary

CCNO (cyclin O, HGNC:18576) is a protein-coding gene on chromosome 5q11.2, encoding Cyclin-O (P22674). Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation.

This gene encodes a member of the cyclin protein family, and the encoded protein is involved in regulation of the cell cycle. Disruption of this gene is associated with primary ciliary dyskinesia-19. Alternative splicing results in multiple transcript variants. This gene, which has a previous symbol of UNG2, was erroneously identified as a uracil DNA glycosylase in PubMed ID: 2001396. A later publication, PubMed ID: 8419333, identified this gene’s product as a cyclin protein family member. The UNG2 symbol is also used as a specific protein isoform name for the UNG gene (GeneID 7374), so confusion exists in the scientific literature and in some databases for these two genes.

Source: NCBI Gene 10309 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 29 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 272 total — 27 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes
• MANE Select transcript: NM_021147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18576
Approved symbol	CCNO
Name	cyclin O
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	UDG2, FLJ22422, UNG2
Ensembl gene	ENSG00000152669
Ensembl biotype	protein_coding
OMIM	607752
Entrez	10309

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000282572, ENST00000501463

RefSeq mRNA: 1 — MANE Select: NM_021147 NM_021147

CCDS: CCDS34157

Canonical transcript exons

ENST00000282572 — 3 exons

Exon	Start	End
ENSE00001006503	55233143	55233608
ENSE00003521875	55232361	55232546
ENSE00003526073	55231152	55231860

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 93.71.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7184 / max 80.2956, expressed in 798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61690	2.0213	718
61688	0.4163	235
61691	0.2673	113
61689	0.0134	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	93.71	gold quality
secondary oocyte	CL:0000655	90.22	gold quality
epithelium of bronchus	UBERON:0002031	90.03	gold quality
bronchial epithelial cell	CL:0002328	89.32	gold quality
bronchus	UBERON:0002185	88.96	gold quality
nasal cavity epithelium	UBERON:0005384	88.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.46	gold quality
right uterine tube	UBERON:0001302	85.51	gold quality
body of pancreas	UBERON:0001150	83.05	gold quality
right lobe of thyroid gland	UBERON:0001119	82.01	gold quality
right testis	UBERON:0004534	81.54	gold quality
left lobe of thyroid gland	UBERON:0001120	81.50	gold quality
left testis	UBERON:0004533	81.49	gold quality
thyroid gland	UBERON:0002046	79.66	gold quality
corpus epididymis	UBERON:0004359	79.25	gold quality
choroid plexus epithelium	UBERON:0003911	78.96	gold quality
testis	UBERON:0000473	78.94	gold quality
adenohypophysis	UBERON:0002196	78.75	gold quality
endometrium epithelium	UBERON:0004811	78.57	silver quality
pituitary gland	UBERON:0000007	78.45	gold quality
nucleus accumbens	UBERON:0001882	76.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.72	gold quality
nasal cavity mucosa	UBERON:0001826	75.92	gold quality
body of stomach	UBERON:0001161	74.53	gold quality
right frontal lobe	UBERON:0002810	74.03	gold quality
caudate nucleus	UBERON:0001873	73.24	gold quality
cauda epididymis	UBERON:0004360	72.48	gold quality
putamen	UBERON:0001874	72.45	gold quality
pancreas	UBERON:0001264	72.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	2754.27
E-MTAB-8221	yes	1830.39
E-CURD-114	yes	1315.71
E-MTAB-9388	yes	6.75
E-ANND-3	yes	6.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CCNO, 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-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-4704-5P	96.13	68.67	608
HSA-MIR-639	88.87	61.76	78
HSA-MIR-487B-3P	88.08	68.35	83

Literature-anchored findings (GeneRIF, showing 7)

• This publication initially attributed ‘uracil-DNA glycosylase’ activity to this gene and named it UNG2, but a later publication (PubMed ID: 8419333) more correctly identified UNG2/CCNO as a member of the cyclin protein family. (PMID:2001396)
• CCNO mutations have a role in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia (PMID:24747639)
• CCNO is mutated more frequently than expected from the rare previous clinical case reports, leads to severe clinical manifestations, and should therefore be considered an important differential diagnosis of mucociliary clearance disorders. (PMID:26777464)
• This study presents the crystal structure of the DDB1-DCAF1-HIV-1-Vpr-uracil-DNA glycosylase (cyclin U) complex. (PMID:27571178)
• Primary ciliary dyskinesia due to CCNO mutations-A genotype-phenotype correlation contribution. (PMID:34102041)
• Bi-allelic mutations in MCIDAS and CCNO cause human infertility associated with abnormal gamete transport. (PMID:34569065)
• This publication corrected the mistaken attribution of uracil DNA glycosylase activity to this gene. (PMID:8419333)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099542
mus_musculus	Ccno	ENSMUSG00000042417
rattus_norvegicus	Ccno	ENSRNOG00000010454
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

Cyclin-O — P22674 (reviewed: P22674)

All UniProt accessions (1): P22674

UniProt curated annotations — full annotation on UniProt →

Function. Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation. Acts downstream of MCIDAS to promote mother centriole amplification and maturation in preparation for apical docking.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Present in respiratory cells (at protein level).

Disease relevance. Ciliary dyskinesia, primary, 29 (CILD29) [MIM:615872] 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. CILD29 patients do not exhibit situs inversus, a congenital abnormality in which visceral organs are opposite to their normal positions (situs solitus) due to lateral transposition. The disease is caused by variants affecting the gene represented in this entry. Marked reduction of cilia in multiciliate cells due to defective mother centriole generation and placement. Remaining cilia correctly express axonemal motor proteins, are motile and do not show beating defects. Defects are probably caused by a strong reduction in the number of multiple motile cilia covering the cell surface in respiratory epithelial cells.

Similarity. Belongs to the cyclin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22674-1	1	yes
P22674-2	2

RefSeq proteins (1): NP_066970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004367	Cyclin_C-dom	Domain
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family

Pfam: PF00134, PF02984

Enzyme classification (BRENDA):

• EC 3.2.2.27 — uracil-DNA glycosylase (BRENDA: 47 organisms, 259 substrates, 76 inhibitors, 79 Km, 70 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
URACIL-CONTAINING CALF THYMUS DNA	0.0004–0.0028	18
URACIL-MISMATCHED DOUBLE-STRANDED DNA	—	18
URACIL-MISMATCHED SINGLE-STRANDED DNA	0.0005–0.0022	8
DOUBLE STRANDED DNA CONTAINING G-U MISMATCH	0.0002–0.001	4
DUMP DNA	0.0004–0.0028	4
URACIL-MISMATCHED DOUBLE-STRANDED DNA WITH U-G M	—	4
URACIL-CONTAINING DOUBLE-STRANDED DNA	0.0001	2
URACIL-CONTAINING SINGLE-STRANDED DNA	—	2
URACIL-MISMATCHED DOUBLE-STRANDED DNA WITH U-A M	0.0007–0.004	2
5-HYDROXYMETHYLURACIL-MISMATCHED DOUBLE-STRANDED	0.0046	1
5-HYDROXYMETHYLURACIL-MISMATCHED DOUBLE-STRANDED	0.0027	1
5-HYDROXYMETHYLURACIL-MISMATCHED SINGLE-STRANDED	0.0038	1
GGACTTCUCTCCTTTCCAGA/TCTGGAAAGGAGGGAAGTCC DUPLEX	0.0003	1
TCCCTTCUCTCCTTTCCTTC/TCCCTTCUCTCCTTTCCTTC DUPLEX	0.0004	1
URACIL-MISMATCHED DOUBLE-STRANDED DNA WITH A-U M	—	0

UniProt features (10 total): sequence variant 3, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22674-F1	79.06	0.59

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 (1): 81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_CILIUM_ORGANIZATION, BILD_E2F3_ONCOGENIC_SIGNATURE, MODULE_206, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, MODULE_392

GO Biological Process (9): G1/S transition of mitotic cell cycle (GO:0000082), mitotic cell cycle (GO:0000278), spermatogenesis (GO:0007283), single fertilization (GO:0007338), cell division (GO:0051301), cilium assembly (GO:0060271), seminiferous tubule development (GO:0072520), multi-ciliated epithelial cell differentiation (GO:1903251), cell projection organization (GO:0030030)

GO Molecular Function (2): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein binding (GO:0005515)

GO Cellular Component (6): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), centriolar satellite (GO:0034451)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cell cycle	1
mitotic nuclear division	1
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
cellular process	1
axoneme assembly	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
male gonad development	1
tube development	1
reproductive structure development	1
columnar/cuboidal epithelial cell differentiation	1
cellular component organization	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein kinase regulator activity	1
binding	1
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
centrosome	1

Protein interactions and networks

STRING

1811 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNO	MCIDAS	D6RGH6	888
CCNO	RSPH4A	Q5TD94	750
CCNO	CCDC39	Q9UFE4	717
CCNO	CCDC40	Q4G0X9	702
CCNO	CDC20B	Q86Y33	681
CCNO	CDK2	P24941	672
CCNO	RSPH1	Q8WYR4	670
CCNO	GMNC	A6NCL1	666
CCNO	DEUP1	Q05D60	661
CCNO	DRC2	Q8IXS2	659
CCNO	RSPH9	Q9H1X1	659
CCNO	CCNL2	Q96S94	657
CCNO	DNAH11	Q96DT5	645
CCNO	FOXJ1	Q92949	633
CCNO	DNAH5	Q8TE73	624

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
CCNO	TLE5	psi-mi:“MI:0915”(physical association)	0.560
Cdk1	PHGDH	psi-mi:“MI:0914”(association)	0.500
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
XRCC1	CCNO	psi-mi:“MI:0915”(physical association)	0.400
CCNO	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
CCNO	FOXN3	psi-mi:“MI:0914”(association)	0.350
TLE5	CCNO	psi-mi:“MI:0915”(physical association)	0.000
ITSN1	CCNO	psi-mi:“MI:0915”(physical association)	0.000
CCNO	VAV2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): CCNO (Two-hybrid), CCNO (Two-hybrid), PRRC2B (Affinity Capture-MS), CDK5 (Affinity Capture-MS), CDK7 (Affinity Capture-MS), CDKN1B (Affinity Capture-MS), CDKN1A (Affinity Capture-MS), CCNO (Affinity Capture-MS), CDK2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), MNAT1 (Affinity Capture-MS), CDK1 (Affinity Capture-MS), SKP2 (Affinity Capture-MS), SATB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A4FV98, A6QPA3, C9J798, C9JJ37, D3YWP0, D3ZVU9, D4A2K4, O43374, O70277, O75382, O95294, P0C6S8, P22674, P57775, Q08DS0, Q0GA42, Q3U410, Q3UGX3, Q4G0W2, Q4V892, Q5SUV1, Q5XIU1, Q6GQU6, Q6IA17, Q6PF15, Q6TDP3, Q6TDP4, Q7TNM2, Q7Z4K8, Q86WI3, Q8CIW5, Q8IZ69, Q8K430, Q8N531, Q8N8L6, Q8NE01, Q8WXI3, Q969K4

Diamond homologs: A2YH60, O01501, O14332, O15995, O48790, P07818, P0C242, P10815, P14785, P15206, P18606, P22674, P24860, P24865, P24868, P24869, P24870, P24871, P25011, P25012, P25322, P30183, P30276, P30278, P30283, P30284, P32943, P34801, P36630, P37882, P37883, P39948, P42524, P46277, P46278, P47829, P50756, P51986, P51987, P51988

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CDK2	“up-regulates activity”	CCNO	phosphorylation
CCNO	“up-regulates activity”	CDK2	binding
CCNO	“up-regulates activity”	CDK1	binding
CCNO	“up-regulates activity”	CDK13	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	9
Uncertain significance	120
Likely benign	96
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1333420	NM_021147.5(CCNO):c.906del (p.Leu303fs)	Pathogenic
139599	NM_021147.5(CCNO):c.248_252dup (p.Gly85fs)	Pathogenic
139600	NM_021147.5(CCNO):c.258_262dup (p.Gln88fs)	Pathogenic
139601	NM_021147.5(CCNO):c.926del (p.Pro309fs)	Pathogenic
139603	NM_021147.5(CCNO):c.263_267dup (p.Val90fs)	Pathogenic
139611	NM_021147.5(CCNO):c.481_482del (p.Leu161fs)	Pathogenic
1453435	NM_021147.5(CCNO):c.307C>T (p.Gln103Ter)	Pathogenic
2025244	NM_021147.5(CCNO):c.327dup (p.Lys110fs)	Pathogenic
2822051	NM_021147.5(CCNO):c.482_483del (p.Leu161fs)	Pathogenic
2835591	NM_021147.5(CCNO):c.476del (p.Asn159fs)	Pathogenic
2963070	NM_021147.5(CCNO):c.192del (p.Ser65fs)	Pathogenic
3649618	NM_021147.5(CCNO):c.248dup (p.Pro84fs)	Pathogenic
3727869	NM_021147.5(CCNO):c.203C>A (p.Ser68Ter)	Pathogenic
411594	NM_021147.5(CCNO):c.638T>C (p.Leu213Pro)	Pathogenic
411596	NM_021147.5(CCNO):c.775C>T (p.Gln259Ter)	Pathogenic
4697405	NM_021147.5(CCNO):c.258_262del (p.Gln88fs)	Pathogenic
4717057	NM_021147.5(CCNO):c.617dup (p.Ala207fs)	Pathogenic
4725916	NM_021147.5(CCNO):c.619_620dup (p.Phe208fs)	Pathogenic
4727414	NM_021147.5(CCNO):c.910dup (p.Arg304fs)	Pathogenic
4755437	NM_021147.5(CCNO):c.379C>T (p.Gln127Ter)	Pathogenic
645504	NM_021147.5(CCNO):c.165del (p.Gly56fs)	Pathogenic
665010	NM_021147.5(CCNO):c.302del (p.Tyr101fs)	Pathogenic
665170	NM_021147.5(CCNO):c.259_268dup (p.Val90fs)	Pathogenic
800814	NM_021147.5(CCNO):c.425del (p.Pro142fs)	Pathogenic
838130	NM_021147.5(CCNO):c.793del (p.Val265fs)	Pathogenic
839570	NM_021147.5(CCNO):c.746del (p.Gln249fs)	Pathogenic
861050	NM_021147.5(CCNO):c.875_897del (p.Asp292fs)	Pathogenic
139602	NM_021147.5(CCNO):c.961C>T (p.Gln321Ter)	Likely pathogenic
2441875	NM_021147.5(CCNO):c.564_567+1delinsTCATCGCTTGCATCGCTTGCATCGCTTGCATCGC	Likely pathogenic
2502875	NM_021147.5(CCNO):c.548T>A (p.Leu183Ter)	Likely pathogenic

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
5:55231857:CCAC:C	acceptor_gain	1.0000
5:55231858:CACC:C	acceptor_gain	1.0000
5:55231859:ACCTG:A	acceptor_loss	1.0000
5:55231862:T:G	acceptor_loss	1.0000
5:55233141:A:AC	donor_gain	1.0000
5:55233142:C:CC	donor_gain	1.0000
5:55231856:TCCAC:T	acceptor_gain	0.9900
5:55231857:CCACC:C	acceptor_gain	0.9900
5:55231858:CAC:C	acceptor_gain	0.9900
5:55231859:AC:A	acceptor_gain	0.9900
5:55231860:CC:C	acceptor_gain	0.9900
5:55231861:C:CC	acceptor_gain	0.9900
5:55233186:T:A	donor_gain	0.9900
5:55231867:C:CT	acceptor_gain	0.9800
5:55232361:C:G	donor_loss	0.9800
5:55233406:T:TA	donor_gain	0.9800
5:55231864:C:CT	acceptor_gain	0.9500
5:55231949:T:TA	donor_gain	0.9500
5:55232543:TCACC:T	acceptor_loss	0.9500
5:55232545:ACCT:A	acceptor_loss	0.9500
5:55232546:CCTGC:C	acceptor_loss	0.9500
5:55232547:C:CA	acceptor_loss	0.9500
5:55232548:T:A	acceptor_loss	0.9500
5:55233139:T:TA	donor_gain	0.9500
5:55232549:G:C	acceptor_loss	0.9400
5:55231579:C:CT	acceptor_gain	0.9300
5:55231938:T:A	donor_gain	0.9300
5:55232552:G:T	acceptor_gain	0.9300
5:55232640:C:A	donor_gain	0.9300
5:55233165:T:TA	donor_gain	0.9300

AlphaMissense

2246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:55232365:T:A	K188I	0.999
5:55231804:G:C	F208L	0.998
5:55231804:G:T	F208L	0.998
5:55231806:A:G	F208L	0.998
5:55232364:T:A	K188N	0.998
5:55232364:T:G	K188N	0.998
5:55231621:A:C	S269R	0.997
5:55231621:A:T	S269R	0.997
5:55231623:T:G	S269R	0.997
5:55231750:G:C	F226L	0.997
5:55231750:G:T	F226L	0.997
5:55231752:A:G	F226L	0.997
5:55232436:G:C	F164L	0.996
5:55232436:G:T	F164L	0.996
5:55232438:A:G	F164L	0.996
5:55232440:C:G	R163P	0.996
5:55231781:A:G	L216P	0.995
5:55231777:C:A	E217D	0.994
5:55231777:C:G	E217D	0.994
5:55231778:T:A	E217V	0.994
5:55231790:A:G	L213P	0.993
5:55232513:A:G	W139R	0.993
5:55232513:A:T	W139R	0.993
5:55232531:G:T	R133S	0.993
5:55232371:G:T	A186D	0.992
5:55232437:A:G	F164S	0.992
5:55232465:A:G	C155R	0.992
5:55232509:A:G	L140P	0.992
5:55232443:T:A	D162V	0.991
5:55231805:A:G	F208S	0.990

dbSNP variants (sampled 300 via entrez): RS1000117529 (5:55233517 T>C,G), RS1000287085 (5:55231577 G>A,T), RS1001263882 (5:55233209 G>A,C), RS1001557714 (5:55231082 C>T), RS1001695267 (5:55232912 C>A), RS1002298395 (5:55233854 G>A,C), RS1003713410 (5:55234980 A>G), RS1004276809 (5:55233742 G>A,T), RS1005251615 (5:55231046 C>T), RS1005422574 (5:55234925 T>C), RS1005930703 (5:55233633 A>G), RS1006324769 (5:55231156 G>C), RS1006403591 (5:55231996 T>C,G), RS1006446744 (5:55230844 C>T), RS1006522076 (5:55234533 C>T)

Disease associations

OMIM: gene MIM:607752 | disease phenotypes: MIM:244400, MIM:615872

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 29	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 29	Definitive	AR

Mondo (2): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 29 (MONDO:0014378)

Orphanet (1): Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

56 total (30 of 56 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:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003676	Progressive
HP:0004313	Decreased circulating immunoglobulin concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008399_7	Cocaine dependence	8.000000e-06

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: yes

ChEMBL targets (2): CHEMBL4105895 (SINGLE PROTEIN), CHEMBL4106152 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

10 potent at pChembl≥5 of 10 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.84	IC50	1.46	nM	STAUROSPORINE
8.83	IC50	1.48	nM	STAUROSPORINE
8.82	IC50	1.51	nM	STAUROSPORINE
8.81	IC50	1.54	nM	STAUROSPORINE
8.76	IC50	1.72	nM	STAUROSPORINE
7.48	IC50	33.1	nM	CHEMBL1708376
7.38	IC50	41.6	nM	CHEMBL4763182
6.97	IC50	108	nM	CHEMBL1906448
6.86	IC50	138	nM	CHEMBL4079206
5.22	Kd	6000	nM	CHEMBL1213412

PubChem BioAssay actives

10 with measured affinity, of 28 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1612678: Inhibition of human CDK2/cyclin-O using histone H1 as substrate by [gamma-33P]-ATP assay	ic50	0.0015	uM
7-bromo-3,6,6-trimethyl-1-(1,3-thiazol-2-yl)-5,7-dihydroindazol-4-one	1731528: Inhibition of CDK2/Cyclin-O (unknown origin) using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method	ic50	0.0331	uM
7-bromo-3,6,6-trimethyl-1-pyrimidin-4-yl-5,7-dihydroindazol-4-one	1731528: Inhibition of CDK2/Cyclin-O (unknown origin) using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method	ic50	0.0416	uM
7-bromo-3,6,6-trimethyl-1-pyridin-2-yl-5,7-dihydroindazol-4-one	1731528: Inhibition of CDK2/Cyclin-O (unknown origin) using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method	ic50	0.1080	uM
2-[(E)-2-(2,6-dichlorophenyl)ethenyl]-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	1479306: Inhibition of CDK2/cyclin O (unknown origin) after 30 mins in presence of [33P]-gamma-ATP by filter binding assay	ic50	0.1380	uM
4-[(E)-2-[(E)-(2,4-dioxo-1H-pyrimidin-6-yl)methylideneamino]oxyethoxyiminomethyl]benzoic acid	498726: Binding affinity to human uracil DNA glycosylase 2	kd	6.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Benzo(a)pyrene	increases expression, decreases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
terbufos	increases methylation	1
potassium bromate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentabromodiphenyl ether	increases expression	1
CPG-oligonucleotide	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
riccardin D	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases methylation	1
Cisplatin	affects expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1220464	Binding	Binding affinity to human uracil DNA glycosylase 2	Impact of linker strain and flexibility in the design of a fragment-based inhibitor. — Nat Chem Biol

Cellosaurus cell lines

5 cell lines: 3 induced pluripotent stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8KW	AMUFAHi001-A	Induced pluripotent stem cell	Female
CVCL_SH46	HAP1 CCNO (-) 1	Cancer cell line	Male
CVCL_SH47	HAP1 CCNO (-) 2	Cancer cell line	Male
CVCL_ZJ20	MHHi016-A	Induced pluripotent stem cell	Male
CVCL_ZJ21	MHHi016-B	Induced pluripotent stem cell	Male

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)