CCDC65

coiled-coil domain containing 65, the group of Cilia and flagella associated|Dynein regulatory complex

Basic information

Region (hg38): 12:48904109-48931840

Links

ENSG00000139537 ∙ NCBI:85478 ∙ OMIM:611088 ∙ HGNC:29937 ∙ Uniprot:Q8IXS2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 27 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 27 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 27	AR	Allergy/Immunology/Infectious; Cardiovascular; Pulmonary	Pulmonary surveillance may be beneficial to assess respiratory 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; Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Allergy/Immunology/Infectious; Pulmonary	23991085; 24094744

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC65 gene.

• Primary ciliary dyskinesia 27 (165 variants)
• not provided (43 variants)
• Inborn genetic diseases (18 variants)
• not specified (7 variants)
• Primary ciliary dyskinesia (3 variants)
• Cough;Anomalous origin of coronary artery from the pulmonary artery;Clinodactyly of the 5th finger (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC65 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				27	5	32
missense			86	6	5	97
nonsense	3		1			4
start loss			1			1
frameshift	5	1	2			8
inframe indel			4			4
splice donor/acceptor (+/-2bp)		2				2
splice region			5	4	1	10
non coding			2	18	23	43
Total	8	3	96	51	33

Highest pathogenic variant AF is 0.00000657

Variants in CCDC65

This is a list of pathogenic ClinVar variants found in the CCDC65 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-48904276-G-A			Benign (May 06, 2019)
12-48904278-T-C			Likely benign (Aug 13, 2019)
12-48904338-T-A		Primary ciliary dyskinesia 27	Uncertain significance (Nov 28, 2022)
12-48904344-A-G		Primary ciliary dyskinesia 27	Uncertain significance (Mar 14, 2022)
12-48904375-C-T		Primary ciliary dyskinesia 27	Likely benign (Jan 29, 2024)
12-48904387-G-A		Primary ciliary dyskinesia 27	Likely benign (Oct 03, 2023)
12-48904391-C-A		Primary ciliary dyskinesia 27	Uncertain significance (Dec 12, 2023)
12-48904392-T-G		Primary ciliary dyskinesia 27	Uncertain significance (Sep 01, 2021)
12-48904408-G-T		Primary ciliary dyskinesia 27	Uncertain significance (Nov 01, 2022)
12-48904409-T-A		Primary ciliary dyskinesia 27	Uncertain significance (Jun 03, 2023)
12-48904414-G-A		Primary ciliary dyskinesia 27	Likely benign (Nov 03, 2022)
12-48904424-G-A		Primary ciliary dyskinesia 27	Uncertain significance (Aug 21, 2022)
12-48904426-G-T		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
12-48904429-G-A		Primary ciliary dyskinesia 27	Uncertain significance (Oct 23, 2019)
12-48904437-A-G		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
12-48904447-G-A		Primary ciliary dyskinesia 27	Likely benign (Aug 21, 2022)
12-48904479-T-C		Primary ciliary dyskinesia 27	Benign (Jan 22, 2024)
12-48904557-C-T			Benign (Nov 10, 2018)
12-48904654-G-T			Benign (Sep 07, 2019)
12-48904720-T-C			Benign (Nov 10, 2018)
12-48904933-T-C		Primary ciliary dyskinesia 27	Likely benign (Sep 09, 2021)
12-48904948-C-A		Primary ciliary dyskinesia 27	Uncertain significance (Mar 15, 2021)
12-48904954-GGCCAAGGAGGAACACAACAGT-G		Primary ciliary dyskinesia 27	Uncertain significance (Oct 18, 2017)
12-48904957-C-T		Primary ciliary dyskinesia 27	Likely benign (Jul 09, 2023)
12-48904958-AAGG-A		Primary ciliary dyskinesia 27 • CCDC65-related disorder	Conflicting classifications of pathogenicity (Aug 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC65	protein_coding	protein_coding	ENST00000320516	8	27731

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.77e-11	0.385	125632	0	116	125748	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.236	265	254	1.04	0.0000128	3231
Missense in Polyphen		52	59.872	0.86853		865
Synonymous	1.31	80	96.4	0.830	0.00000464	861
Loss of Function	1.09	19	24.8	0.765	0.00000140	290

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000598	0.000597
Ashkenazi Jewish	0.00427	0.00428
East Asian	0.000327	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000299	0.000299
Middle Eastern	0.000327	0.000326
South Asian	0.000523	0.000523
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the nexin-dynein regulatory complex (N- DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes (By similarity). Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with DRC1 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules (PubMed:24094744). {ECO:0000250|UniProtKB:A8JB22, ECO:0000269|PubMed:24094744}.

Recessive Scores

• pRec: 0.0935

Intolerance Scores

• loftool: 0.958
• rvis_EVS: 1.4
• rvis_percentile_EVS: 94.73

Haploinsufficiency Scores

• pHI: 0.140
• hipred: N
• hipred_score: 0.167
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0264

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc65

Zebrafish Information Network

• Gene name: ccdc65
• Affected structure: ciliated olfactory receptor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: regulation of cilium movement;cilium assembly;cilium-dependent cell motility;axonemal dynein complex assembly
• Cellular component: cellular_component;axonemal dynein complex;axoneme;motile cilium
• Molecular function: molecular_function