CCNO

cyclin O, the group of Cyclins

Basic information

Region (hg38): 5:55231152-55233608

Previous symbols: [ "CCNU" ]

Links

ENSG00000152669 ∙ NCBI:10309 ∙ OMIM:607752 ∙ HGNC:18576 ∙ Uniprot:P22674 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 29 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 29 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 29 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 29 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 29 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary 29	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	24747639; 24824133

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCNO gene.

• Primary ciliary dyskinesia (18 variants)
• Primary ciliary dyskinesia 29 (7 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCNO gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				40	1	41
missense	1	1	72	8	2	84
nonsense	2	2				4
start loss						0
frameshift	17	2				19
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1	1			2
splice region		1		3		4
non coding			2	8	5	15
Total	20	6	77	56	8

Highest pathogenic variant AF is 0.000145

Variants in CCNO

This is a list of pathogenic ClinVar variants found in the CCNO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-55231323-G-C			Likely benign (May 24, 2021)
5-55231388-G-A		Primary ciliary dyskinesia	Uncertain significance (Jan 13, 2023)
5-55231388-G-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
5-55231411-G-A		Primary ciliary dyskinesia	Likely benign (Dec 27, 2023)
5-55231416-G-C		Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2021)
5-55231421-G-A		Primary ciliary dyskinesia	Likely benign (Jan 15, 2024)
5-55231426-C-G		Primary ciliary dyskinesia	Likely benign (Jan 25, 2024)
5-55231429-G-A		Primary ciliary dyskinesia • CCNO-related disorder	Likely benign (Apr 30, 2018)
5-55231431-G-A		Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2021)
5-55231432-A-G		Primary ciliary dyskinesia	Likely benign (Aug 09, 2022)
5-55231439-G-A		Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2022)
5-55231442-G-A		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
5-55231446-T-C		Inborn genetic diseases	Likely benign (Sep 25, 2023)
5-55231450-T-C		Primary ciliary dyskinesia	Uncertain significance (Jan 13, 2023)
5-55231463-AG-A		Primary ciliary dyskinesia 29	Likely pathogenic (Jan 27, 2020)
5-55231467-G-A		Primary ciliary dyskinesia 29 • Primary ciliary dyskinesia	Likely pathogenic (Dec 12, 2022)
5-55231471-C-T		Primary ciliary dyskinesia • CCNO-related disorder	Benign (Jan 16, 2024)
5-55231478-A-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
5-55231479-T-G		Primary ciliary dyskinesia	Uncertain significance (Aug 27, 2021)
5-55231483-G-C		Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2021)
5-55231488-C-T		Primary ciliary dyskinesia	Benign/Likely benign (Jan 25, 2024)
5-55231501-CG-C		Primary ciliary dyskinesia 29	Pathogenic (Jun 01, 2014)
5-55231521-AG-A		Primary ciliary dyskinesia 29	Pathogenic (Jan 03, 2022)
5-55231530-GCCGCGAGACCCGCAGCATGCGGT-G		Primary ciliary dyskinesia	Pathogenic (Oct 23, 2023)
5-55231533-G-A		Primary ciliary dyskinesia	Benign (Dec 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCNO	protein_coding	protein_coding	ENST00000282572	3	2529

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00355	0.852	125648	0	55	125703	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.136	198	193	1.03	0.00000869	2183
Missense in Polyphen		63	67.128	0.93851		816
Synonymous	-0.431	99	93.7	1.06	0.00000447	775
Loss of Function	1.22	5	8.94	0.559	3.82e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000215	0.000190
Ashkenazi Jewish	0.00	0.00
East Asian	0.000756	0.000653
Finnish	0.00	0.00
European (Non-Finnish)	0.000259	0.000220
Middle Eastern	0.000756	0.000653
South Asian	0.000357	0.000327
Other	0.000530	0.000489

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:24747639, ECO:0000269|PubMed:26777464}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:24747639, ECO:0000269|PubMed:26777464}. Note=The disease is caused by mutations 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 (PubMed:24747639). {ECO:0000269|PubMed:24747639}.

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.605
• rvis_EVS: 0.48
• rvis_percentile_EVS: 79.25

Haploinsufficiency Scores

• pHI: 0.0803
• hipred: Y
• hipred_score: 0.723
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.812

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ccno
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;mitotic cell cycle;protein phosphorylation;regulation of mitotic nuclear division;positive regulation of cell population proliferation;response to drug;positive regulation of cell cycle;cell division;cilium assembly;multi-ciliated epithelial cell differentiation
• Cellular component: cyclin-dependent protein kinase holoenzyme complex;nucleus;cytoplasm
• Molecular function: protein kinase activity;cyclin-dependent protein serine/threonine kinase regulator activity;protein kinase binding