CCDC65

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

Basic information

Region (hg38): 12:48904110-48931840

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
• primary ciliary dyskinesia 27 (Definitive), mode of inheritance: AR

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 (11 variants)
• Anomalous origin of coronary artery from the pulmonary artery;Cough;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. These statistics are base on transcript: . Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				34	5	39
missense			96	5	5	106
nonsense	4	1	1			6
start loss			1			1
frameshift	7	1	2			10
splice donor/acceptor (+/-2bp)		2				2
Total	11	4	100	39	10

Highest pathogenic variant AF is 0.000019706

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